U.S. patent application number 15/304151 was filed with the patent office on 2017-02-09 for ammonia-oxidizing nitrosomonas eutropha strain d23.
The applicant listed for this patent is AOBIOME LLC. Invention is credited to Ioannis Gryllos, Spiros Jamas, Larry Weiss, David R. Whitlock.
Application Number | 20170037363 15/304151 |
Document ID | / |
Family ID | 54324705 |
Filed Date | 2017-02-09 |
United States Patent
Application |
20170037363 |
Kind Code |
A1 |
Whitlock; David R. ; et
al. |
February 9, 2017 |
AMMONIA-OXIDIZING NITROSOMONAS EUTROPHA STRAIN D23
Abstract
This disclosure provides, inter alia, an optimized strain of
Nitrosomonas eutropha (N. eutropha) designated D23, D23-100, or AOB
D23-100. N. eutropha bacteria disclosed in this application have
desirable properties, e.g., optimized properties, such as the
ability to suppress growth of pathogenic bacteria, and an enhanced
ability to produce nitric oxide and nitric oxide precursors. The N.
eutropha herein may be used, for instance, to treat diseases
associated with low nitrite levels, skin diseases, and diseases
caused by pathogenic bacteria.
Inventors: |
Whitlock; David R.;
(Cambridge, MA) ; Jamas; Spiros; (Cambridge,
MA) ; Weiss; Larry; (San Francisco, CA) ;
Gryllos; Ioannis; (Brookline, MA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
AOBIOME LLC |
Cambridge |
MA |
US |
|
|
Family ID: |
54324705 |
Appl. No.: |
15/304151 |
Filed: |
April 15, 2015 |
PCT Filed: |
April 15, 2015 |
PCT NO: |
PCT/US2015/025909 |
371 Date: |
October 14, 2016 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
62053588 |
Sep 22, 2014 |
|
|
|
62012811 |
Jun 16, 2014 |
|
|
|
62002084 |
May 22, 2014 |
|
|
|
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61P 37/08 20180101;
A61K 35/744 20130101; A61P 15/00 20180101; A61Q 15/00 20130101;
A61Q 19/02 20130101; A61Q 17/04 20130101; A61K 9/0014 20130101;
A61P 9/10 20180101; A61K 35/747 20130101; C12Q 1/02 20130101; A61P
17/02 20180101; A61P 9/00 20180101; A61P 9/04 20180101; A61P 17/06
20180101; A61Q 19/00 20130101; A61P 31/18 20180101; C07K 14/195
20130101; A61P 43/00 20180101; A61Q 19/04 20130101; A61K 35/745
20130101; A61P 17/04 20180101; A61P 35/00 20180101; A61L 15/36
20130101; C12N 1/00 20130101; A61P 9/12 20180101; A61P 13/12
20180101; A61P 37/06 20180101; A61P 3/04 20180101; C12R 1/01
20130101; A61P 3/10 20180101; A61P 17/14 20180101; A61K 8/99
20130101; A61K 48/00 20130101; A61P 9/08 20180101; A61P 31/04
20180101; C12N 1/20 20130101; C12Q 1/689 20130101; A01N 63/00
20130101; A61P 17/00 20180101; A61P 17/10 20180101; A61K 35/74
20130101 |
International
Class: |
C12N 1/20 20060101
C12N001/20; A61K 35/747 20060101 A61K035/747; A61K 35/744 20060101
A61K035/744; C12Q 1/02 20060101 C12Q001/02; A61K 8/99 20060101
A61K008/99; A61Q 17/04 20060101 A61Q017/04; A01N 63/00 20060101
A01N063/00; C12R 1/01 20060101 C12R001/01; A61K 35/74 20060101
A61K035/74; A61K 35/745 20060101 A61K035/745 |
Foreign Application Data
Date |
Code |
Application Number |
Apr 15, 2014 |
GR |
20140100217 |
Mar 13, 2015 |
GR |
20150100115 |
Claims
1. A purified preparation of optimized Nitrosomonas eutropha (N.
eutropha) bacterium having at least one property selected from: an
optimized growth rate; an optimized NH.sub.4.sup.+ oxidation rate;
and an optimized resistance to NH.sub.4.sup.+.
2. The preparation of N. eutropha bacterium of claim 1, wherein the
optimized growth rate is a rate allowing a continuous culture of N.
eutropha at an OD600 (optical density at 600 nm) of about 0.15-0.18
to reach an OD600 of about 0.5-0.6 in about 1-2 days.
3. The preparation of N. eutropha bacterium of claim 1 or 2,
wherein the optimized growth rate is a doubling time of about 8
hours when cultured under batch culture conditions.
4. The preparation of N. eutropha bacterium of any of claims 1-3,
wherein the optimized NH.sub.4.sup.+ oxidation rate is a rate of at
least about 125 micromoles per minute of oxidizing NH.sub.4.sup.+
to NO.sub.2.sup.-.
5. The preparation of N. eutropha bacterium of any of claims 1-4,
wherein the optimized resistance to NH.sub.4.sup.+ is an ability to
grow in medium comprising about 200 mM NH.sub.4.sup.+ for at least
about 48 hours.
6. The preparation of N. eutropha bacterium of any of claims 1-5,
which has at least two properties selected from an optimized growth
rate, an optimized NH.sub.4.sup.+ oxidation rate, and an optimized
resistance to NH.sub.4.sup.+.
7. The preparation of N. eutropha bacterium of claim 1-6, which has
an optimized growth rate, an optimized NH.sub.4.sup.+ oxidation
rate, and an optimized resistance to NH.sub.4.sup.+.
8. The preparation of N. eutropha bacterium of any of claims 1-7,
which comprises a chromosome that hybridizes under very high
stringency to SEQ ID NO: 1.
9. The preparation of N. eutropha bacterium of any of claim 1-8,
which comprises an AmoA protein having an identity to SEQ ID NO: 6
or 12 selected from at least about 80%, 85%, 90%, 95%, 98%, 99%,
99.5%, and 100% identical, an AmoB protein having an identity to
SEQ ID NO: 8 or 14 selected from at least about 80%, 85%, 90%, 95%,
98%, 99%, 99.5%, and 100% identical, an amoC gene having an
identity to SEQ ID NO: 4, 10, or 16 selected from at least about
80%, 85%, 90%, 95%, 98%, 99%, 99.5%, and 100% identical, a
hydroxylamine oxidoreductase protein having an identity to SEQ ID
NO: 18, 20, or 22 selected from at least 80%, 85%, 90%, 95%, 98%,
99%, 99.5%, and 100% identical, a cytochrome c554 protein having an
identity to SEQ ID NO: 24, 26, or 28 selected from at least about
80%, 85%, 90%, 95%, 98%, 99%, 99.5%, and 100% identical, or a
cytochrome c.sub.M552 protein having an identity to SEQ ID NO: 30
or 32 selected from at least about 80%, 85%, 90%, 95%, 98%, 99%,
99.5%, and 100% identical.
10. The preparation of N. eutropha bacterium of any of claims 1-9,
which comprises 1-5, 5-10, 10-15, 15-20, 20-25, 25-30, or all of
the sequence characteristics of Table 2.
11. The preparation of N. eutropha bacterium of claim 10, which
comprises an AmoA1 or AmoA2 protein having (or gene encoding) a
mutation relative to N. eutropha strain C91 at position 1, e.g., a
V at position 1.
12. The preparation of N. eutropha bacterium of any of claims
10-11, which comprises an AmoA1 or AmoA2 protein having (or gene
encoding) a mutation relative to N. eutropha strain C91 at position
160, e.g., an L at position 160.
13. The preparation of N. eutropha bacterium of any of claims
10-12, which comprises an AmoA1 or AmoA2 protein having (or gene
encoding) a mutation relative to N. eutropha strain C91 at position
167, e.g., an A at position 167.
14. The preparation of N. eutropha bacterium of any of claims
10-13, which comprises an AmoB1 or AmoB2 protein having (or gene
encoding) a mutation relative to N. eutropha strain C91 at position
33, e.g., a V at position 33.
15. The preparation of N. eutropha bacterium of any of claims
10-14, which comprises an AmoB1 or AmoB2 protein having (or gene
encoding) a mutation relative to N. eutropha strain C91 at position
165, e.g., an I at position 165.
16. The preparation of N. eutropha bacterium of any of claims
10-15, which comprises an AmoC3 protein having (or gene encoding) a
mutation relative to N. eutropha strain C91 at position 79, e.g.,
an A at position 79.
17. The preparation of N. eutropha bacterium of any of claims
10-16, which comprises an AmoC3 protein having (or gene encoding) a
mutation relative to N. eutropha strain C91 at position 271, e.g.,
a V at position 271.
18. The preparation of N. eutropha bacterium of any of claims
10-17, which comprises a Hao1, Hao2, or Hao3 protein having (or
gene encoding) a mutation relative to N. eutropha strain C91 at
position 85, e.g., an S at position 85.
19. The preparation of N. eutropha bacterium of any of claims
10-18, which comprises a Hao1, Hao2, or Hao3 protein having (or
gene encoding) a mutation relative to N. eutropha strain C91 at
position 312, e.g., an E at position 312.
20. The preparation of N. eutropha bacterium of any of claims
10-19, which comprises a Hao1 protein having (or gene encoding) a
mutation relative to N. eutropha strain C91 at position 163, e.g.,
an A at position 163.
21. The preparation of N. eutropha bacterium of any of claims
10-20, which comprises a c554 CycA1, c554 CycA2, or c554 CycA3
protein having (or gene encoding) a mutation relative to N.
eutropha strain C91 at position 65, e.g., a T at position 65.
22. The preparation of N. eutropha bacterium of any of claims
10-21, which comprises a c554 CycA1 protein having (or gene
encoding) a mutation relative to N. eutropha strain C91 at position
186, e.g., a T at position 186.
23. The preparation of N. eutropha bacterium of any of claims
10-22, which comprises a c.sub.M552 CycB1 or c.sub.M552 CycB2
protein having (or gene encoding) a mutation relative to N.
eutropha strain C91 at position 63, e.g., a V at position 63.
24. The preparation of N. eutropha bacterium of any of claims
10-23, which comprises a c.sub.M552 CycB1 or c.sub.M552 CycB2
protein having (or gene encoding) a mutation relative to N.
eutropha strain C91 at position 189, e.g., a P at position 189.
25. The preparation of N. eutropha bacterium of any of claims
10-24, which comprises a c.sub.M552 CycB1 or c.sub.M552 CycB2
protein having (or gene encoding) a mutation relative to N.
eutropha strain C91 at position 206, e.g., an insE at position
206.
26. The preparation of N. eutropha bacterium of any of claims
10-25, which comprises a c.sub.M552 CycB1 or c.sub.M552 CycB2
protein having (or gene encoding) a mutation relative to N.
eutropha strain C91 at position 207, e.g., an insE at position
207.
27. The preparation of N. eutropha bacterium of any of claims
10-26, which comprises a c.sub.M552 CycB1 protein having (or gene
encoding) a mutation relative to N. eutropha strain C91 at position
195, e.g., an insD at position 195.
28. The preparation of N. eutropha bacterium of any of claims
10-27, which comprises a c.sub.M552 CycB1 protein having (or gene
encoding) a mutation relative to N. eutropha strain C91 at position
196, e.g., an insD at position 196.
29. The preparation of N. eutropha bacterium of any of claims
10-28, which comprises a c.sub.M552 CycB1 protein having (or gene
encoding) a mutation relative to N. eutropha strain C91 at position
197, e.g., an insD at position 197.
30. The preparation of N. eutropha bacterium of any of the
preceding claims, which comprises at least one structural
difference, e.g., at least one mutation, relative to a wild-type
bacterium such as N. eutropha strain C91.
31. The preparation of N. eutropha bacterium of any of the
preceding claims, which comprises a nucleic acid that can be
amplified using a pair of primers described herein, e.g., a primer
comprising a sequence of SEQ ID NO: 64 and a primer comprising a
sequence of SEQ ID NO: 65.
32. The preparation of N. eutropha bacterium of any of the
preceding claims, which comprises a nucleic acid or protein at
least 80%, 85%, 90%, 95%, 98%, 99%, 99.5%, or 100% identical to a
gene of FIG. 6 or a protein encoded by a gene of FIG. 6.
33. The preparation of N. eutropha bacterium of any of the
preceding claims, which comprises a nucleic acid or protein at
least 80%, 85%, 90%, 95%, 98%, 99%, 99.5%, or 100% identical to a
sequence of any of SEQ ID NOS: 64-66 or a protein encoded by a
sequence of any of SEQ ID NOS: 64-66.
34. An N. eutropha bacterium, or a purified preparation thereof,
comprising a mutation in an ammonia monooxygenase gene, a
hydroxylamine oxidoreductase gene, a cytochrome c554 gene, or a
cytochrome c.sub.m552 gene relative to a wild-type bacterium such
as N. eutropha strain C91.
35. The N. eutropha bacterium, or a purified preparation thereof,
of claim 34, wherein said mutation is in the amoA1 gene.
36. The N. eutropha bacterium, or a purified preparation thereof,
of claim 34, wherein said mutation is in the amoA2 gene.
37. The N. eutropha bacterium, or a purified preparation thereof,
of claim 34, wherein said mutation is in the amoB1 gene.
38. The N. eutropha bacterium, or a purified preparation thereof,
of claim 34, wherein said mutation is in the amoB2 gene.
39. The N. eutropha bacterium, or a purified preparation thereof,
of claim 34, wherein said mutation is in the amoC3 gene.
40. The N. eutropha bacterium, or a purified preparation thereof,
of any of claims 34-39, wherein said mutation is at a position
described herein, e.g., in Table 2.
41. The N. eutropha bacterium, or a purified preparation thereof,
of any of claims 34-39, wherein said mutation is a mutation
described herein, e.g., in Table 2.
42. The N. eutropha bacterium, or a purified preparation thereof,
of claim 34, wherein said mutation is in the hao1 gene.
43. The N. eutropha bacterium, or a purified preparation thereof,
of claim 34, wherein said mutation is in the hao2 gene.
44. The N. eutropha bacterium, or a purified preparation thereof,
of claim 34, wherein said mutation is in the hao3 gene.
45. The N. eutropha bacterium, or a purified preparation thereof,
of any of claims 42-44, wherein said mutation is at a position
described herein, e.g., in Table 2.
46. The N. eutropha bacterium, or a purified preparation thereof,
of any of claims 42-44, wherein said mutation is a mutation
described herein, e.g., in Table 2.
47. The N. eutropha bacterium, or a purified preparation thereof,
of claim 34, wherein said mutation is in the c554 cycA1 gene.
48. The N. eutropha bacterium, or a purified preparation thereof,
of claim 34, wherein said mutation is in the c554 cycA2 gene.
49. The N. eutropha bacterium, or a purified preparation thereof,
of claim 34, wherein said mutation is in the c554 cycA3 gene.
50. The N. eutropha bacterium, or a purified preparation thereof,
of any of claims 47-49, wherein said mutation is at a position
described herein, e.g., in Table 2.
51. The N. eutropha bacterium, or a purified preparation thereof,
of any of claims 47-49, wherein said mutation is a mutation
described herein, e.g., in Table 2.
52. The N. eutropha bacterium, or a purified preparation thereof,
of claim 34, wherein said mutation is in the c.sub.M552 cycB1
gene.
53. The N. eutropha bacterium, or a purified preparation thereof,
of claim 34, wherein said mutation is in the c554 cycB2 gene.
54. The N. eutropha bacterium, or a purified preparation thereof,
of any of claims 52-53, wherein said mutation is at a position
described herein, e.g., in Table 2.
55. The N. eutropha bacterium, or a purified preparation thereof,
of any of claims 52-53, wherein said mutation is a mutation
described herein, e.g., in Table 2.
56. The purified preparation of optimized N. eutropha bacterium of
claim 1, comprising a mutation in an ammonia monooxygenase gene, a
hydroxylamine oxidoreductase gene, a cytochrome c554 gene, or a
cytochrome c.sub.m552 gene.
57. The purified preparation of optimized N. eutropha bacterium of
claim 56, wherein said mutation is in the amoA1 gene.
58. The purified preparation of optimized N. eutropha bacterium of
claim 56, wherein said mutation is in the amoA2 gene.
59. The purified preparation of optimized N. eutropha bacterium of
claim 56, wherein said mutation is in the amoB1 gene.
60. The purified preparation of optimized N. eutropha bacterium of
claim 56, wherein said mutation is in the amoB2 gene.
61. The purified preparation of optimized N. eutropha bacterium of
claim 56, wherein said mutation is in the amoC3 gene.
62. The purified preparation of optimized N. eutropha bacterium of
any of claims 57-61, wherein said mutation is at a position
described herein, e.g., in Table 2.
63. The purified preparation of optimized N. eutropha bacterium of
any of claims 57-61, wherein said mutation is a mutation described
herein, e.g., in Table 2.
64. The purified preparation of optimized N. eutropha bacterium of
claim 56, wherein said mutation is in the hao1 gene.
65. The purified preparation of optimized N. eutropha bacterium of
claim 56, wherein said mutation is in the hao2 gene.
66. The purified preparation of optimized N. eutropha bacterium of
claim 56, wherein said mutation is in the hao3 gene.
67. The purified preparation of optimized N. eutropha bacterium of
any of claims 64-66, wherein said mutation is at a position
described herein, e.g., in Table 2.
68. The purified preparation of optimized N. eutropha bacterium of
any of claims 64-66, wherein said mutation is a mutation described
herein, e.g., in Table 2.
69. The purified preparation of optimized N. eutropha bacterium of
claim 56, wherein said mutation is in the c554 cycA1 gene.
70. The purified preparation of optimized N. eutropha bacterium of
claim 56, wherein said mutation is in the c554 cycA2 gene.
71. The purified preparation of optimized N. eutropha bacterium of
claim 56, wherein said mutation is in the c554 cycA3 gene.
72. The purified preparation of optimized N. eutropha bacterium of
any of claims 69-71, wherein said mutation is at a position
described herein, e.g., in Table 2.
73. The purified preparation of optimized N. eutropha bacterium of
any of claims 69-71, wherein said mutation is a mutation described
herein, e.g., in Table 2.
74. The purified preparation of optimized N. eutropha bacterium of
claim 56, wherein said mutation is in the c.sub.M552 cycB1
gene.
75. The purified preparation of optimized N. eutropha bacterium of
claim 56, wherein said mutation is in the c.sub.M552 cycB2
gene.
76. The purified preparation of optimized N. eutropha bacterium of
any of claims 56, 74, and 75, wherein said mutation is at a
position described herein, e.g., in Table 2.
77. The purified preparation of optimized N. eutropha bacterium of
any of claims 56, 74, and 75, wherein said mutation is a mutation
described herein, e.g., in Table 2.
78. The N. eutropha bacterium, or a purified preparation thereof,
of claim 34, which has a mutation in at least 2, 3, 4, 5, 6, 7, 8,
9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25,
26, 27, 28, 29, 30, 31, 32, 33, 34, or 35 positions of one or more
of amoA1 gene, amoA2 gene, amoB1 gene, amoB2 gene, amoC3 gene, hao1
gene, hao2 gene, hao3 gene, c554 cycA1 gene, c554 cycA2 gene, c554
cycA3 gene, c.sub.M552 cycB1 gene, and c554 cycB2 gene.
79. The purified preparation of optimized N. eutropha bacterium of
claim 56, which has a mutation in at least 2, 3, 4, 5, 6, 7, 8, 9,
10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26,
27, 28, 29, 30, 31, 32, 33, 34, or 35 positions of one or more of
amoA1 gene, amoA2 gene, amoB1 gene, amoB2 gene, amoC3 gene, hao1
gene, hao2 gene, hao3 gene, c554 cycA1 gene, c554 cycA2 gene, c554
cycA3 gene, c.sub.M552 cycB1 gene, and c554 cycB2 gene.
80. A N. eutropha bacterium comprising a chromosome that hybridizes
at high stringency to SEQ ID NO: 1.
81. The N. eutropha bacterium of claim 80, wherein the chromosome
hybridizes at very high stringency to SEQ ID NO: 1.
82. The N. eutropha bacterium of claim 80 or 81, which comprises at
least one of the genes of FIGS. 6-8, or a gene with at least 80%
identity thereto.
83. The N. eutropha bacterium of claim 80 or 81, which comprises at
least one of the genes of FIGS. 6-8.
84. The N. eutropha bacterium of any of claims 80-82, which lacks
any plasmid that is at least about 80% identical to SEQ ID NO: 2 or
SEQ ID NO: 3.
85. The N. eutropha bacterium of claim any of claims 80-84, which
lacks any plasmid.
86. A N. eutropha bacterium comprising one or more of an AmoA1 gene
at least about 98.9% identical to SEQ ID NO: 7 and an amoA2 gene at
least about 98.8% identical to SEQ ID NO: 13.
87. A N. eutropha bacterium comprising one or more of an AmoA1
protein at least about 99.0% identical to SEQ ID NO: 6 and an AmoA2
protein at least about 99.0% identical to SEQ ID NO: 12.
88. A N. eutropha bacterium comprising one or more of an amoB1 gene
at least about 99.2% identical to SEQ ID NO: 9 and an amoB2 gene at
least about 99.2% identical to SEQ ID NO: 15.
89. The N. eutropha bacterium of claim 88, further comprising one
or more of an AmoA1 or amoA2 gene at least about 98.9% identical to
SEQ ID NO: 7 or 13.
90. An N. eutropha bacterium comprising one or more of an AmoB1
protein at least about 99.6% identical to SEQ ID NO: 8 or an AmoB1
protein at least about 99.6% identical to SEQ ID NO: 14.
91. The N. eutropha bacterium of claim 90, further comprising one
or more of an AmoA1 protein at least about 99.0% identical to SEQ
ID NO: 6 and an AmoA2 protein at least about 99.0% identical to SEQ
ID NO: 12.
92. An N. eutropha bacterium comprising one or more of an amoC1
gene at least about 99.9% identical to SEQ ID NO: 5, an amoC2 gene
at least about 99.9% identical to SEQ ID NO: 11, and an amoC3 gene
at least about 99.0% identical to SEQ ID NO: 17.
93. The N. eutropha bacterium of claim 92, further comprising one
or more of an amoA1 gene at least about 98.9% identical to SEQ ID
NO: 7, an amo2 gene at least about 98.9% identical to SEQ ID NO:
13, an amoB1 gene at least about 99.2% identical to SEQ ID NO: 9,
and an amoB2 gene at least about 99.2% identical to SEQ ID NO:
15.
94. A N. eutropha bacterium comprising an AmoC3 protein at least
about 99.4% identical to SEQ ID NO: 16.
95. The N. eutropha bacterium of claim 94, further comprising one
or more of an AmoA1 protein at least about 99.0% identical to SEQ
ID NO: 6, an AmoA2 protein at least about 99.0% identical to SEQ ID
NO: 12, an AmoB1 protein at least about 99.6% identical to SEQ ID
NO: 8, and an AmoB1 protein at least about 99.6% identical to SEQ
ID NO: 14.
96. A N. eutropha bacterium comprising one or more of a hao1 gene
at least about 99.1% identical to SEQ ID NO: 19, a hao2 gene at
least about 99.5% identical to SEQ ID NO: 21, and a hao3 gene at
least about 99.3% identical to SEQ ID NO: 23.
97. The N. eutropha bacterium of claim 96, further comprising one
or more of an amoA1 gene at least about 98.9% identical to SEQ ID
NO: 7, an amo2 gene at least about 98.9% identical to SEQ ID NO:
13, an amoB1 gene at least about 99.2% identical to SEQ ID NO: 9,
an amoB2 gene at least about 99.2% identical to SEQ ID NO: 15, an
amoC1 gene at least about 99.9% identical to SEQ ID NO: 5, an amoC2
gene at least about 99.9% identical to SEQ ID NO: 11, and an amoC3
gene at least about 99.0% identical to SEQ ID NO: 17.
98. A N. eutropha bacterium comprising one or more of a Hao1
protein at least about 99.6% identical to SEQ ID NO: 18, a Hao2
protein at least about 99.7% identical to SEQ ID NO: 20, and a Hao3
protein at least about 99.7% identical to SEQ ID NO: 22.
99. The N. eutropha bacterium of claim 98, further comprising an
AmoA1 protein at least about 99.0% identical to SEQ ID NO: 6, an
AmoA2 protein at least about 99.0% identical to SEQ ID NO: 12, an
AmoB1 protein at least about 99.6% identical to SEQ ID NO: 8, an
AmoB1 protein at least about 99.6% identical to SEQ ID NO: 14, or
an AmoC3 protein at least about 99.4% identical to SEQ ID NO:
16.
100. An N. eutropha bacterium comprising one or more of a cycA1
gene at least about 98.1% identical to SEQ ID NO: 25, a cycA2 gene
at least about 98.8% identical to SEQ ID NO: 27, and a cycA3 gene
at least about 99.4% identical to SEQ ID NO: 28.
101. The N. eutropha bacterium of claim 100, further comprising one
or more of an amoA1 gene at least about 98.9% identical to SEQ ID
NO: 7, an amo2 gene at least about 98.9% identical to SEQ ID NO:
13, an amoB1 gene at least about 99.2% identical to SEQ ID NO: 9,
an amoB2 gene at least about 99.2% identical to SEQ ID NO: 15, an
amoC1 gene at least about 99.9% identical to SEEQ ID NO: 5, an
amoC2 gene at least about 99.9% identical to SEQ ID NO: 11, an
amoC3 gene at least about 99.0% identical to SEQ ID NO: 17, a hao1
gene at least about 99.1% identical to SEQ ID NO: 19, a hao2 gene
at least about 99.5% identical to SEQ ID NO: 21, and a hao3 gene at
least about 99.3% identical to SEQ ID NO: 23.
102. An N. eutropha bacterium comprising one or more of a CycA1
protein at least about 99.2% identical to SEQ ID NO: 24, a CycA2
protein at least about 99.7% identical to SEQ ID NO: 26, and a
CycA3 protein at least about 99.7% identical to SEQ ID NO: 28.
103. The N. eutropha bacterium of claim 102, further comprising one
or more of an AmoA1 protein at least about 99.0% identical to SEQ
ID NO: 6, an AmoA2 protein at least about 99.0% identical to SEQ ID
NO: 12, an AmoB1 protein at least about 99.6% identical to SEQ ID
NO: 8, an AmoB1 protein at least about 99.6% identical to SEQ ID
NO: 14, an AmoC3 protein at least about 99.4% identical to SEQ ID
NO: 16, a Hao1 protein at least about 99.6% identical to SEQ ID NO:
18, a Hao2 protein at least about 99.7% identical to SEQ ID NO: 20,
and a Hao3 protein at least about 99.7% identical to SEQ ID NO:
22.
104. A N. eutropha bacterium comprising one or more of a cycB1 gene
at least about 96.8% identical to SEQ ID NO: 31 and a cycB2 gene at
least about 97.2% identical to SEQ ID NO: 33.
105. The N. eutropha bacterium of claim 104, further comprising one
or more of an amoA1 gene at least about 98.9% identical to SEQ ID
NO: 7, an amo2 gene at least about 98.9% identical to SEQ ID NO:
13, an amoB1 gene at least about 99.2% identical to SEQ ID NO: 9,
an amoB2 gene at least about 99.2% identical to SEQ ID NO: 15, an
amoC1 gene at least about 99.9% identical to SEQ ID NO: 5, an amoC2
gene at least about 99.9% identical to SEQ ID NO: 11, an amoC3 gene
at least about 99.0% identical to SEQ ID NO: 17, a hao1 gene at
least about 99.1% identical to SEQ ID NO: 19, a hao2 gene at least
about 99.5% identical to SEQ ID NO: 21, a hao3 gene at least about
99.3% identical to SEQ ID NO: 23, a cycA1 gene at least about 98.1%
identical to SEQ ID NO: 25, a cycA2 gene at least about 98.8%
identical to SEQ ID NO: 27, and a cycA3 gene at least about 99.4%
identical to SEQ ID NO: 28.
106. A N. eutropha bacterium comprising one or more of a CycB1
protein at least about 97.2% identical to SEQ ID NO: 30 or a CycB2
protein at least about 98.8% identical to SEQ ID NO: 32.
107. The N. eutropha bacterium of claim 106, further comprising one
or more of an AmoA1 protein at least about 99.0% identical to SEQ
ID NO: 6, an AmoA2 protein at least about 99.0% identical to SEQ ID
NO: 12, an AmoB1 protein at least about 99.6% identical to SEQ ID
NO: 8, an AmoB1 protein at least about 99.6% identical to SEQ ID
NO: 14, an AmoC3 protein at least about 99.4% identical to SEQ ID
NO: 16, a Hao1 protein at least about 99.6% identical to SEQ ID NO:
18, a Hao2 protein at least about 99.7% identical to SEQ ID NO: 20,
a Hao3 protein at least about 99.7% identical to SEQ ID NO: 22, a
CycA1 protein at least about 99.2% identical to SEQ ID NO: 24, a
CycA2 protein at least about 99.7% identical to SEQ ID NO: 26, and
a CycA3 protein at least about 99.7% identical to SEQ ID NO:
28.
108. A N. eutropha bacterium comprising one or more genes according
to SEQ ID NOS: 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31,
and 33.
109. A N. eutropha bacterium comprising one or more proteins
according to SEQ ID NOS: 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24,
26, 28, 30, and 32.
110. A N. eutropha bacterium comprising a protein that is mutant
relative to N. eutropha strain C91 at at least 1, 2, 3, 4, 5, 10,
15, 20, 25, 30, or all of the amino acid positions listed in Table
2.
111. A N. eutropha bacterium comprising proteins that are mutant
relative to N. eutropha strain C91 at all of the amino acid
positions listed in Table 2.
112. The N. eutropha bacterium of any one of claims 1-111, which is
transgenic.
113. The N. eutropha bacterium of any one of claims 80-112, having
at least one property selected from an optimized growth rate, an
optimized NH.sub.4.sup.+ oxidation rate, and an optimized
resistance to NH.sub.4.sup.+.
114. The N. eutropha bacterium of claim 113, which has at least two
properties selected from an optimized growth rate, an optimized
NH.sub.4.sup.+ oxidation rate, and an optimized resistance to
NH.sub.4.sup.+.
115. The N. eutropha bacterium of claim 113, which has an optimized
growth rate, an optimized NH.sub.4.sup.+ oxidation rate, and an
optimized resistance to NH.sub.4.sup.+.
116. A composition comprising the N. eutropha bacterium of any one
of claims 1-115, wherein the composition is substantially free of
other organisms.
117. A composition comprising the N. eutropha bacterium of one any
of claims 1-115 and further comprising a second organism, wherein
the composition is substantially free of other organisms.
118. The composition of claim 117, wherein the second organism is
an ammonia oxidizing bacterium.
119. The composition of claim 117, wherein the second organism is
selected from the group consisting of Nitrosomonas, Nitrosococcus,
Nitrosospria, Nitrosocystis, Nitrosolobus, Nitrosovibrio,
Lactobacillus, Streptococcus, and Bifidobacter, and combinations
thereof.
120. A composition comprising a cell suspension of an actively
dividing culture of N. eutropha bacteria having an OD600 of at
least about 0.2, wherein the composition is substantially free of
other organisms.
121. A composition for topical administration, comprising the N.
eutropha bacterium of any one of claims 1-115 and a
pharmaceutically or cosmetically acceptable excipient suitable for
topical administration.
122. The composition of claim 121, which is substantially free of
other organisms.
123. The composition of claim 121, further comprising a second
organism.
124. The composition of claim 123, wherein the second organism is
an ammonia oxidizing bacterium.
125. The composition of claim 123, wherein the second organism is
selected from the group consisting of Nitrosomonas, Nitrosococcus,
Nitrosospria, Nitrosocystis, Nitrosolobus, Nitrosovibrio,
Lactobacillus, Streptococcus, and Bifidobacter, and combinations
thereof.
126. The composition of any of claims 121-125, which is provided as
or disposed in a powder, cosmetic, cream, stick, aerosol, salve,
wipe, or bandage.
127. The composition of any of claims 121-126, which further
comprises a moisturizing agent, deodorizing agent, scent, colorant,
insect repellant, cleansing agent, or UV-blocking agent.
128. The composition of any of claims 121-127, wherein the
excipient comprises an anti-adherent, binder, coat, disintegrant,
filler, flavor, color, lubricant, glidant, sorbent, preservative,
or sweetener.
129. The composition of any of claims 121-128, wherein the
concentration of N. eutropha in the composition is about
10.sup.11-10.sup.12 CFU/L.
130. The composition of any of claims 121-129, wherein the
concentration of N. eutropha in the composition is about 10.sup.9
CFU/ml.
131. The composition of any of claims 121-130, wherein the mass
ratio of N. eutropha to pharmaceutical excipient is in a range of
about 0.1 grams per liter to about 1 gram per liter.
132. A composition comprising at least about 1,000 L at about
10.sup.12 CFUs/L of the N. eutropha bacterium of any one of claims
1-115.
133. A composition comprising at least about 1, 2, 5, 10, 20, 50,
100, 200, or 500 g of the N. eutropha bacterium of any one of
claims 1-115, e.g., as a dry formulation such as a powder.
134. An article of clothing comprising the N. eutropha of any one
of claims 1-115, e.g., at a concentration that provides one or more
of a treatment or prevention of a skin disorder, a treatment or
prevention of a disease or condition associated with low nitrite
levels, a treatment or prevention of body odor, a treatment to
supply nitric oxide to a subject, or a treatment to inhibit
microbial growth.
135. The article of clothing of claim 134, which is packaged.
136. The article of clothing of claim 134-135, which is packaged in
a material that is resistant to gaseous exchange or resistant to
water.
137. A cloth comprising the N. eutropha of any one of claims
1-115.
138. A yarn comprising the N. eutropha of any one of claims
1-115.
139. A thread comprising the N. eutropha of any one of claims
1-115.
140. A method of obtaining, e.g., manufacturing, an N. eutropha
bacterium having an optimized growth rate, an optimized
NH.sub.4.sup.+ oxidation rate, or an optimized resistance to
NH.sub.4.sup.+, comprising: (a) culturing the bacterium under
conditions that select for one or more of an optimized growth rate,
an optimized NH.sub.4.sup.+ oxidation rate, or an optimized
resistance to NH.sub.4.sup.+, thereby producing a culture; (b)
testing a sample from the culture for an optimized growth rate, an
optimized NH.sub.4.sup.+ oxidation rate, or an optimized resistance
to NH.sub.4.sup.+; and (c) repeating the culturing and testing
steps until a bacterium having an optimized growth rate, an
optimized NH.sub.4.sup.+ oxidation rate, or an optimized resistance
to NH.sub.4.sup.+ is obtained.
141. The method of claim 140, further comprising a step of
obtaining an N. eutropha bacterium from a source.
142. The method of claim 141, wherein the source is soil or the
skin of an individual.
143. The method of claim 142, wherein culturing the bacterium under
conditions that select for one or more of an optimized growth rate,
an optimized NH.sub.4.sup.+ oxidation rate, or an optimized
resistance to NH.sub.4.sup.+ comprises culturing the bacterium in
N. europae medium that comprises about 200 mM NH.sub.4.sup.+.
144. The method of claim 143, which comprises a step of creating an
axenic culture.
145. The method of claim 143 or 144, which comprises a step of
co-culturing the N. eutropha together with at least one other type
of ammonia oxidizing bacteria.
146. The method of any of claims 140-145, wherein the N. eutropha
of step (a) lack an optimized growth rate, an optimized
NH.sub.4.sup.+ oxidation rate, and an optimized resistance to
NH.sub.4.sup.+.
147. The method of any of claims 140-146, wherein step (c)
comprises repeating the culturing and testing steps until a
bacterium having at least two of an optimized growth rate, an
optimized NH.sub.4.sup.+ oxidation rate, and an optimized
resistance to NH.sub.4.sup.+ is obtained.
148. An N. eutropha bacterium produced by the method of any of
claims 140-147.
149. A method of testing a preparation of N. eutropha, comprising:
assaying the N. eutropha for one or more of an optimized growth
rate, an optimized NH.sub.4.sup.+ oxidation rate, or an optimized
resistance to NH.sub.4.sup.+; and if the N. eutropha has one or
more of an optimized growth rate, an optimized NH.sub.4.sup.+
oxidation rate, or an optimized resistance to NH.sub.4.sup.+,
classifying the N. eutropha as accepted.
150. The method of claim 149, further comprising a step of testing
the preparation for contaminating organisms.
151. The method of any of claims 149-150, further comprising a step
of removing a sample from the preparation and conducting testing on
the sample.
152. The method of any of claims 149-151, further comprising
testing medium in which the N. eutropha is cultured.
153. The method of any of claims 149-152, further comprising
packaging N. eutropha from the preparation into a package.
154. The method of any of claims 149-153, further comprising
placing N. eutropha from the preparation into commerce.
155. A method of producing, e.g., manufacturing N. eutropha,
comprising contacting N. eutropha with culture medium and culturing
the N. eutropha until an OD600 of at least about 0.5 is
reached.
156. The method of claim 155, further comprising assaying the N.
eutropha and culture medium for contaminating organisms.
157. The method of any of claims 155-156, further comprising
assaying the N. eutropha for one or more of an optimized growth
rate, an optimized NH.sub.4.sup.+ oxidation rate, or an optimized
resistance to NH.sub.4.sup.+.
158. The method of any of claims 155-157, which comprises producing
at least at least about 1,000 L per day at about 10.sup.12 CFUs/L
of N. eutropha.
159. A method of producing, e.g., manufacturing, N. eutropha,
comprising contacting N. eutropha with culture medium and culturing
the N. eutropha until about at least about 1,000 L at about
10.sup.12 CFUs/L N. eutropha are produced.
160. The method of claim 159, further comprising a step of assaying
the N. eutropha for one or more of an optimized growth rate, an
optimized NH.sub.4.sup.+ oxidation rate, or an optimized resistance
to NH.sub.4.sup.+.
161. The method of any of claims 159-160, further comprising a step
of testing the N. eutropha or culture medium for contaminating
organisms.
162. The method of any of claims 159-161, wherein the N. eutropha
brought into contact with the culture medium is an N. eutropha
having one or more of an optimized growth rate, an optimized
NH.sub.4.sup.+ oxidation rate, or an optimized resistance to
NH.sub.4.sup.+.
163. A method of producing, e.g., manufacturing N. eutropha,
comprising: (a) contacting N. eutropha with a culture medium; and
(b) culturing the N. eutropha for 1-2 days, thereby creating a
culture, until the culture reaches an OD600 of about 0.5-0.6.
164. The method of claim 163, further comprising a step of assaying
the N. eutropha for one or more of an optimized growth rate, an
optimized NH.sub.4.sup.+ oxidation rate, or an optimized resistance
to NH.sub.4.sup.+.
165. The method of any of claims 163-164, further comprising a step
of testing the culture for contaminating organisms.
166. The method of any of claims 163-165, wherein the N. eutropha
of step (a) is an N. eutropha having one or more of an optimized
growth rate, an optimized NH.sub.4.sup.+ oxidation rate, or an
optimized resistance to NH.sub.4.sup.+.
167. The method of any of claims 163-166, which comprises producing
at least at least about 1,000 L per day at about 10.sup.12 CFUs/L
of N. eutropha.
168. An N. eutropha bacterium produced by the method of any of
claims 155-167.
169. A preparation of N. eutropha made by the method of any of
claims 155-167.
170. The preparation of claim 169, wherein the preparation
comprises at least about 0.1 to about 100 milligrams (mg) of N.
eutropha.
171. A reaction mixture comprising N. eutropha at an optical
density of about 0.5 to about 0.6.
172. A method of producing N. eutropha-bearing clothing, comprising
contacting an article of clothing with of the N. eutropha of any
one of claims 1-115.
173. The method of claim 172, which comprises producing at least
10, 100, or 1000 articles of clothing.
174. The method of claim 172, which comprises contacting the
article of clothing with at least 10.sup.10 CFUs of N.
eutropha.
175. The method of claim 172, further comprising packaging the
clothing.
176. A method of obtaining a formulation of N. eutropha, combining
contacting N. eutropha of any of claims 1-115 with a
pharmaceutically or cosmetically acceptable excipient.
177. The method of claim 176, further comprising mixing the N.
eutropha and the excipient.
178. The method of claim 176, which is performed under conditions
that are substantially free of contaminating organisms.
179. A method of packaging N. eutropha, comprising assembling N.
eutropha of any of claim 1-115 into a package.
180. The method of claim 179, wherein the package is resistant to
gaseous exchange or resistant to water.
181. The method of claim 179, wherein the package is permeable to
gaseous exchange, NH.sub.3, NH.sub.4.sup.+, or NO.sub.2.sup.-.
182. A method of inhibiting microbial growth on a subject's skin,
comprising topically administering to a subject in need thereof an
effective dose of the N. eutropha bacteria of any one of claims
1-115.
183. The method of claim 182, wherein the effective dose is
approximately 1.5.times.10.sup.10 CFU.
184. The method of any of claims 182-183, wherein the
administration is performed twice per day.
185. The method of any of claims 182-184, wherein the subject is a
human.
186. The method of any of claims 182-185, wherein the microbial
growth to be inhibited is growth of Pseudomonas aeruginosa,
Staphylococcus aureus, Streptococcus pyogenes, or Acinetobacter
baumannii.
187. A method of supplying nitric oxide to a subject, comprising
positioning an effective dose of the N. eutropha bacteria of any
one of claims 1-115 in close proximity to the subject.
188. A method of reducing body odor, comprising topically
administering to a subject in need thereof an effective dose of the
N. eutropha bacteria of any one of claims 1-115.
189. A method of treating a disease associated with low nitrite
levels, comprising topically administering to a subject in need
thereof a therapeutically effective dose of the N. eutropha
bacteria of any of claims 1-115.
190. The method of claim 189, wherein the disease is HIV
dermatitis, infection in a diabetic foot ulcer, atopic dermatitis,
acne, e.g., acne vulgaris, eczema, contact dermatitis, allergic
reaction, psoriasis, skin infections, vascular disease, vaginal
yeast infection, a sexually transmitted disease, heart disease,
atherosclerosis, baldness, leg ulcers secondary to diabetes or
confinement to bed, angina, particularly chronic, stable angina
pectoris, ischemic diseases, congestive heart failure, myocardial
infarction, ischemia reperfusion injury, laminitis, hypertension,
hypertrophic organ degeneration, Raynaud's phenomenon, fibrosis,
fibrotic organ degeneration, allergies, autoimmune sensitization,
end stage renal disease, obesity, impotence, or cancer.
191. A method of treating a skin disorder, comprising topically
administering to a subject in need thereof a therapeutically
effective dose of the N. eutropha bacteria of any of claims
1-115.
192. The method of claim 191, wherein the skin disorder is acne,
e.g., acne vulgaris, rosacea, eczema, or psoriasis.
193. The method of claim 191, wherein the skin disorder is an
ulcer, e.g., venous ulcer, e.g., leg ulcer, e.g., venous leg ulcer,
e.g., infection in a diabetic foot ulcer.
194. The method of any one of claims 191-193, wherein topically
administering comprises pre-treating the subject with N. eutropha,
e.g., an N. eutropha of any of claims 1-115.
195. The method of any one of claims 191-194, wherein topically
administering comprises topically administering prior to occurrence
of the skin disorder.
196. The method of any one of claims 191-195, wherein topically
administering comprises topically administering subsequent to
occurrence of the skin disorder.
197. A method of promoting wound healing or closure, comprising
administering to a wound an effective dose of the N. eutropha
bacteria of any of claims 1-115.
198. The method of claim 197, wherein the wound comprises one or
more undesirable bacteria, e.g., pathogenic bacteria.
199. The method of claim 197, wherein the wound comprises
Staphylococcus aureus, Pseudomonas aeruginosa, or Acinetobacter
baumannii.
200. The method of claim 197, wherein the N. eutropha is
administered to the subject prior to occurrence of the wound.
201. The method of claim 197, wherein administering to the wound
comprises administering to the subject prior to occurrence of the
wound.
202. The method of any one of claims 197-201, further comprising
administering N. eutropha to the wound subsequent to occurrence of
the wound.
203. A method of killing or inhibiting growth of pathogenic
bacteria comprising contacting, e.g., applying, N. eutropha
bacteria, e.g., an N. eutropha bacterium of any of claims 1-115, to
the skin.
204. The method of claim 203, wherein the pathogenic bacteria
contribute to one or more of the following conditions: HIV
dermatitis, an ulcer, e.g., venous ulcer, e.g., leg ulcer, e.g.,
venous leg ulcer, e.g., infection in a diabetic foot ulcer, atopic
dermatitis, acne, e.g., acne vulgaris, eczema, contact dermatitis,
allergic reaction, psoriasis, uticaria, rosacea, skin infections,
vascular disease, vaginal yeast infection, a sexually transmitted
disease, heart disease, atherosclerosis, baldness, leg ulcers
secondary to diabetes or confinement to bed, angina, particularly
chronic, stable angina pectoris, ischemic diseases, congestive
heart failure, myocardial infarction, ischemia reperfusion injury,
laminitis, hypertension, hypertrophic organ degeneration, Raynaud's
phenomenon, fibrosis, fibrotic organ degeneration, allergies,
autoimmune sensitization, end stage renal disease, obesity,
impotence, pneumonia, primary immunodeficiency, epidermal lysis
bulosa, or cancer.
205. The method of claim 204, wherein the condition is an ulcer,
e.g., venous ulcer, e.g., leg ulcer, e.g., venous leg ulcer, e.g.,
infection in a diabetic foot ulcer.
206. The method of claim 204, wherein the condition is a venous leg
ulcer.
207. The method of claim 204, wherein the condition is acne, e.g.,
acne vulgaris.
208. The method of claim 204, wherein the condition is acne
vulgaris.
209. The method of any one of claims 203-208, wherein the
pathogenic bacteria is one or more of Propionibacterium acnes,
Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus
pyogenes, or Acinetobacter baumannii.
210. The method of any one of claims 203-209, further comprising
determining whether the subject is in need of killing or inhibiting
growth of pathogenic bacteria, e.g., determining that the subject
is in need of killing or inhibiting growth of pathogenic
bacteria.
211. The method of any one of claims 203-210, further comprising
selecting the subject in need of killing or inhibiting growth of
pathogenic bacteria.
212. A method of changing a composition of a skin microbiome of a
subject comprising: administering, e.g., applying, a preparation
comprising ammonia oxidizing bacteria to a surface of the skin,
wherein the amount and frequency of administration, e.g.,
application, is sufficient to reduce the proportion of pathogenic
bacteria on the surface of the skin.
213. The method of claim 212, further comprising, selecting the
subject on the basis of the subject being in need of a reduction in
the proportion of pathogenic bacteria on the surface of the
skin.
214. The method of any one of claims 212-213, wherein the
preparation comprises at least one of ammonia, ammonium salts, and
urea.
215. The method of any one of claims 212-214, wherein the
preparation comprises a controlled release material, e.g., slow
release material.
216. The method of any one of claims 212-215, wherein the
preparation of ammonia oxidizing bacteria, further comprises an
excipient, e.g., one of a pharmaceutically acceptable excipient or
a cosmetically acceptable excipient.
217. The method of claim 216, wherein the excipient, e.g., one of
the pharmaceutically acceptable excipient and the cosmetically
acceptable excipient, is suitable for one of topical, nasal,
pulmonary, and gastrointestinal administration.
218. The method of any one of claims 216-217, wherein the
excipient, e.g., one of the pharmaceutically acceptable excipient
and the cosmetically acceptable excipient, is a surfactant.
219. The method of claim 218, wherein the surfactant is selected
from the group consisting of cocamidopropyl betaine (ColaTeric
COAB), polyethylene sorbitol ester (e.g., Tween 80), ethoxylated
lauryl alcohol (RhodaSurf 6 NAT), sodium laureth sulfate/lauryl
glucoside/cocamidopropyl betaine (Plantapon 611 L UP), sodium
laureth sulfate (e.g., RhodaPex ESB 70 NAT), alkyl polyglucoside
(e.g., Plantaren 2000 N UP), sodium laureth sulfate (Plantaren
200), Dr. Bronner's Castile soap, Lauramine oxide (ColaLux Lo),
sodium dodecyl sulfate (SDS), polysulfonate alkyl polyglucoside
(PolySufanate 160 P), sodium lauryl sulfate (Stepanol-WA Extra K),
and any combination thereof.
220. The method of any one of claims 212-219, wherein the
preparation is substantially free of other organisms.
221. The method of any one of claims 212-220, wherein the
preparation is disposed in a powder, cosmetic, cream, stick,
aerosol, salve, wipe, or bandage.
222. The method of any one of claims 212-221, wherein the
preparation is provided as a powder, cosmetic, cream, stick,
aerosol, salve, wipe, or bandage.
223. The method of any one of claims 212-222, wherein the
preparation comprises a moisturizing agent, deodorizing agent,
scent, colorant, insect repellant, cleansing agent, or UV-blocking
agent.
224. The method of any one of claims 216-217, wherein the
excipient, e.g., the pharmaceutically acceptable excipient or the
cosmetically acceptable excipient, comprises an anti-adherent,
binder, coat, disintegrant, filler, flavor, color, lubricant,
glidant, sorbent, preservative, or sweetener.
225. The method of any one of claims 212-224, wherein the
preparation comprising ammonia oxidizing bacteria comprises about
10.sup.8 to about 10.sup.14 CFU/L.
226. The method of claim 225, wherein the preparation comprises
between about 1.times.10.sup.9 CFU/L to about 10.times.10.sup.9
CFU/L.
227. The method of any one of claims 212-226, wherein the
preparation comprising ammonia oxidizing bacteria comprises between
about 50 milligrams (mg) and about 1000 mg of ammonia oxidizing
bacteria.
228. The method of any one of claims 216-227, wherein the mass
ratio of ammonia oxidizing bacteria to the excipient, e.g., the
pharmaceutically acceptable excipient or the cosmetically
acceptable excipient is in a range of about 0.1 grams per liter to
about 1 gram per liter.
229. The method of any one of claims 212-228, wherein the
preparation of ammonia oxidizing bacteria are useful for treating
or preventing a skin disorder, a treatment or prevention of a
disease or condition associated with low nitrite levels, a
treatment or prevention of body odor, a treatment to supply nitric
oxide to a subject, or a treatment to inhibit microbial growth,
e.g., pathogenic bacterial growth.
230. The method of any one of claims 212-229, wherein the ammonia
oxidizing bacteria is selected from the group consisting of
Nitrosomonas, Nitrosococcus, Nitrosospria, Nitrosocystis,
Nitrosolobus, Nitrosovibrio, and combinations thereof.
231. The method of any one of claims 212-230, wherein the
preparation comprises an organism selected from the group
consisting of Lactobacillus, Streptococcus, Bifidobacter, and
combinations thereof.
232. The method of any one of claims 212-230, wherein the
preparation is substantially free of organisms other than ammonia
oxidizing bacteria.
233. The method of any one of claims 212-232, wherein the
preparation of ammonia oxidizing bacteria comprises ammonia
oxidizing bacteria in a growth state.
234. The method of any one of claims 212-232, wherein the
preparation of ammonia oxidizing bacteria comprises ammonia
oxidizing bacteria in a storage state.
235. The method of any one of claims 212-234, to deliver a cosmetic
product.
236. The method of any one of claims 212-234, to deliver a
therapeutic product.
237. The method of any one of claims 212-236, wherein the
preparation is useful for treatment of at least one of HIV
dermatitis, infection in a diabetic foot ulcer, atopic dermatitis,
acne, e.g., acne vulgaris, eczema, contact dermatitis, allergic
reaction, psoriasis, uticaria, rosacea, skin infections, vascular
disease, vaginal yeast infection, a sexually transmitted disease,
heart disease, atherosclerosis, baldness, leg ulcers secondary to
diabetes or confinement to bed, angina, particularly chronic,
stable angina pectoris, ischemic diseases, congestive heart
failure, myocardial infarction, ischemia reperfusion injury,
laminitis, hypertension, hypertrophic organ degeneration, Raynaud's
phenomenon, fibrosis, fibrotic organ degeneration, allergies,
autoimmune sensitization, end stage renal disease, obesity,
impotence, pneumonia, primary immunodeficiency, epidermal lysis
bulosa, or cancer.
238. The method of claim 237, wherein the preparation is useful for
treatment of at least one of acne, e.g., acne vulgaris, eczema,
psoriasis, uticaria, rosacea, and skin infections.
239. The method of any one of claims 212-238, wherein the
preparation is provided in a container, the preparation and the
container having a weight of less than about 50, 100, 200, 300,
400, 500, 600, 700, 800, 900, 1000, 1500, or 2000 grams.
240. The method of any one of claims 212-239, wherein the
preparation has less than about 0.1% to about 10% of
surfactant.
241. The method of any one of claims 212-240, wherein the
preparation is substantially free of surfactant.
242. The method of any one of claims 212-241, wherein the
preparation comprises a chelator.
243. The method of any one of claims 212-242, wherein the
preparation is applied about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,
13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 times per
day.
244. The method of any one of claims 212-243, wherein the
preparation is applied one time per day.
245. The method of any one of claims 212-243, wherein the
preparation is applied two times per day.
246. The method of any one of claims 212-245, wherein the
preparation is applied for about 1-3, 3-5, 5-7, 7-9, 5-10, 10-14,
12-18, 12-21, 21-28, 28-35, 35-42, 42-49, 49-56, 46-63, 63-70,
70-77, 77-84, or 84-91 days.
247. The method of any one of claims 212-246, wherein the
preparation is applied for about 16 days.
248. The method of any one of claims 212-247 further comprising
obtaining a sample from the surface of the skin.
249. The method of claim 248, further comprising isolating DNA of
bacteria in the sample.
250. The method of any one of claims 248-249, further comprising
sequencing DNA of bacteria in the sample.
251. The method of any one of claims 212-250, wherein administering
the ammonia oxidizing bacteria provides for an increase in the
proportion of non-pathogenic bacteria on the surface.
252. The method of claim 251, wherein the non-pathogenic bacteria
is commensal non-pathogenic bacteria.
253. The method of claim 252, wherein the non-pathogenic bacteria
is commensal non-pathogenic bacteria of the genus
Staphylococcus.
254. The method of claim 253, wherein the non-pathogenic bacteria
is commensal non-pathogenic bacteria Staphylococcus
epidermidis.
255. The method of any one of claims 252-254, wherein the
non-pathogenic bacteria of the genus Staphylococcus is, or is
identified as being, increased after about 2 weeks.
256. The method of claim 255, wherein the non-pathogenic bacteria
Staphylococcus epidermidis is, or is identified as being, increased
after about 2 weeks.
257. The method of any one of claims 212-256, wherein potentially
pathogenic or disease associated Propionibacteria is, or is
identified as being, reduced after about 2 weeks.
258. The method of any one of claims 212-257, wherein potentially
pathogenic or disease associated Stenotrophomonas is, or is
identified as being, reduced after about 2 weeks.
259. The method of any one of claims 212-258, wherein the surface
of the skin comprises a wound.
260. A method of treating acne e.g., acne vulgaris, by the method
of any one of claims 212-259.
261. A method of treating eczema by the method of any one of claims
212-259.
262. A method of treating psoriasis by the method of any one of
claims 212-259.
263. A method of treating uticaria by the method of any one of
claims 212-259.
264. A method of treating rosacea by the method of any one of
claims 212-259.
265. A method of treating a skin infection by the method of any one
of claims 212-259.
266. A method of reducing an amount of undesirable bacteria on a
surface of a subject by the method of any one of claims
212-258.
267. A nucleic acid comprising a sequence of 15-100 consecutive
nucleotides from within SEQ ID NO: 66, or a reverse complement
thereof, provided that the nucleic acid has a non-naturally
occurring sequence, or another modification, e.g., a label, or
both.
268. The nucleic acid of claim 267, wherein the sequence of 15-100
consecutive nucleotides is a sequence not found in N. Eutropha
strain C91.
269. The nucleic acid of claim 267 or 268, further comprising a
heterologous sequence 5' to the sequence of 15-100 consecutive
nucleotides from within SEQ ID NO: 66.
270. The nucleic acid of claim 267 or 268, further comprising a
heterologous sequence 3' to the sequence of 15-100 consecutive
nucleotides from within SEQ ID NO: 66.
271. The nucleic acid of claim 267 or 268, further comprising a
first heterologous sequence 5' to the sequence of 15-100
consecutive nucleotides from within SEQ ID NO: 66 and a second
heterologous sequence 3' to the sequence of 15-100 consecutive
nucleotides from within SEQ ID NO: 66.
272. The nucleic acid of any of claims 267-271, which has a length
of 15-20, 20-25, 25-30, 30-24, or 25-40 nucleotides.
273. The nucleic acid of any of claims 267-272, which is bound,
e.g., covalently bound, to a detectable label, e.g., a fluorescent
label.
274. A composition comprising: a first nucleic acid comprising
15-100 consecutive nucleotides from within SEQ ID NO: 66; and a
second nucleic acid comprising 15-100 consecutive nucleotides from
within a reverse complement of SEQ ID NO: 66, provided that the
first nucleic acid or the second nucleic acid or both has a
non-naturally occurring sequence or a modification such as a label,
or both.
275. The composition of claim 274, wherein the first nucleic acid,
the second nucleic acid, or each of the first nucleic acid and
second nucleic acid does not comprise a sequence found in N.
Eutropha strain C91.
276. The composition of claim 274 or 275, wherein the first nucleic
acid, the second nucleic acid, or each of the first nucleic acid
and second nucleic acid further comprises a heterologous sequence
5' to the sequence of 15-100 consecutive nucleotides from within
SEQ ID NO: 66.
277. The composition of any of claims 274-276, wherein the first
nucleic acid, the second nucleic acid, or each of the first nucleic
acid and second nucleic acid further comprises a heterologous
sequence 3' to the sequence of 15-100 consecutive nucleotides from
within SEQ ID NO: 66.
278. The composition of any of claims 274-277, wherein the first
nucleic acid, the second nucleic acid, or each of the first nucleic
acid and second nucleic acid has a length of 15-20, 20-25, 25-30,
30-24, or 25-40 nucleotides.
279. The composition of any of claims 274-278, wherein the first
nucleic acid, the second nucleic acid, or each of the first nucleic
acid and second nucleic acid is bound, e.g., covalently bound, to a
detectable label, e.g., a fluorescent label.
280. A nucleic acid consisting of the sequence AATCTGTCTCCACAGGCAGC
(SEQ ID NO: 64).
281. A nucleic acid consisting of the sequence TATACCCACCACCCACGCTA
(SEQ ID NO: 65).
282. A molecule comprising the nucleic acid of claim 280 or 281 and
a detectable label, e.g., a fluorescent label.
283. A composition comprising a first nucleic acid consisting of
the sequence AATCTGTCTCCACAGGCAGC (SEQ ID NO: 64) and a second
nucleic acid consisting of the sequence TATACCCACCACCCACGCTA (SEQ
ID NO: 65).
284. A composition comprising: a first molecule comprising (i) a
first nucleic acid consisting of the sequence AATCTGTCTCCACAGGCAGC
(SEQ ID NO: 64) and optionally comprising (ii) a detectable label,
e.g., a fluorescent label; and a second molecule comprising (i) a
second nucleic acid consisting of the sequence TATACCCACCACCCACGCTA
(SEQ ID NO: 65) and optionally comprising (ii) a detectable label,
e.g., a fluorescent label.
285. A method of detecting whether a D23 N. eutropha nucleic acid
is present in a sample, comprising: performing a polymerase chain
reaction (PCR) on the sample using primers specific to N. eutropha
D23, and determining whether a PCR product is produced, wherein the
presence of a PCR product indicates that the D23 N. eutropha
nucleic acid was present in the sample.
Description
[0001] This application claims priority to Greek Patent Application
Number 20140100217, filed Apr. 15, 2014, U.S. Provisional
Application No. 62/002,084, filed May 22, 2014, U.S. Provisional
Application No. 62/012,811, filed Jun. 16, 2014, U.S. Provisional
Application No. 62/053,588, filed Sep. 22, 2014, and Greek Patent
Application Number 20150100115, filed Mar. 13, 2015, the contents
of which are incorporated herein by reference in their
entireties.
SEQUENCE LISTING
[0002] The instant application contains a Sequence Listing which
has been submitted electronically in ASCII format and is hereby
incorporated by reference in its entirety. Said ASCII copy, created
on Apr. 13, 2015, is named N2060-7001WO.txt and is 3,590,980 bytes
in size.
BACKGROUND
[0003] Beneficial bacteria can be used to suppress the growth of
pathogenic bacteria. Bacteria and other microorganisms are
ubiquitous in the environment. The discovery of pathogenic bacteria
and the germ theory of disease have had a tremendous effect on
health and disease states. Bacteria are a normal part of the
environment of all living things. In the gut, these bacteria are
not pathogenic under normal conditions, and in fact improve health
by rendering the normal intestinal contents less hospitable for
disease causing organisms. Disease prevention is accomplished in a
number of ways: nutrients are consumed, leaving less for pathogens;
conditions are produced, such as pH and oxygen tension, which are
not hospitable for pathogens; compounds are produced that are toxic
to pathogens; pathogens are consumed as food by these
microorganisms; less physical space remains available for
pathogens; and specific binding sites are occupied leaving fewer
binding sites available for pathogens. The presence of these
desirable bacteria is seen as useful in preventing disease
states.
[0004] There is a need in the art for improved beneficial bacteria
that can suppress the growth of pathogenic bacteria.
SUMMARY
[0005] This disclosure provides, inter alia, an optimized strain of
Nitrosomonas eutropha (N. eutropha) designated D23, D23-100 or AOB
D23-100, the terms which may be used interchangeably throughout the
disclosure.
[0006] Ammonia oxidizing bacterial of the genus Nitrosomonas are
ubiquitous Gram-negative obligate chemolithoautotrophic bacteria
with a unique capacity to generate energy exclusively from the
conversion of ammonia to nitrite.
[0007] N. eutropha bacteria disclosed in this application have
desirable, e.g. optimized, properties such as the ability to
suppress growth of pathogenic bacteria, and an enhanced ability to
produce nitric oxide (NO) and nitric oxide (NO.sub.2.sup.-)
precursors. The N. eutropha, e.g., optimized N. eutropha, e.g.,
purified preparations of optimized N. eutropha herein may be used,
for instance, to treat diseases, e.g., diseases associated with low
nitrite levels, skin disorders, and diseases caused by pathogenic
bacteria. When referring to N. eutropha throughout the disclosure,
it may be referring to an optimized strain of N. eutropha or a
purified preparation of optimized N. eutropha.
[0008] The present disclosure provides, inter alia, a Nitrosomonas
eutropha (N. eutropha) bacterium, e.g., an optimized N. eutropha,
e.g., a purified preparation of optimized N. eutropha, having at
least one property selected from: [0009] an optimized growth rate;
[0010] an optimized NH.sub.4.sup.+ oxidation rate; and [0011] an
optimized resistance to ammonium ion (NH.sub.4.sup.+).
[0012] The bacterium is optionally axenic.
[0013] In embodiments, the optimized growth rate is a rate allowing
a continuous culture of N. eutropha at an OD600 (optical density at
600 nm) of about 0.15-0.18 to reach an OD600 of about 0.5-0.6 in
about 1-2 days. In embodiments, optimized growth rate is a doubling
time of about 8 hours when cultured under batch culture conditions.
In embodiments, the optimized NH.sub.4.sup.+ oxidation rate is a
rate of at least about 125 micromoles per minute of oxidizing
NH.sub.4.sup.+ to NO.sub.2.sup.-. In embodiments, the optimized
resistance to NH.sub.4.sup.+ is an ability to grow in medium
comprising about 200 mM NH.sub.4.sup.+ for at least about 48
hours.
[0014] In some embodiments, the purified preparation of optimized
N. eutropha bacterium (which is optionally axenic) has at least two
properties selected from an optimized growth rate, an optimized
NH.sub.4.sup.+ oxidation rate, and an optimized resistance to
NH.sub.4.sup.+. In some embodiments, the purified preparation of
optimized N. eutropha bacterium (which is optionally axenic) has an
optimized growth rate, an optimized NH.sub.4.sup.+ oxidation rate,
and an optimized resistance to NH.sub.4.sup.+. In some embodiments,
the purified preparation of optimized N. eutropha bacterium (which
is optionally axenic) comprises a chromosome that hybridizes under
very high stringency to SEQ ID NO: 1.
[0015] In some embodiments, the purified preparation of optimized
N. eutropha bacterium (which is optionally axenic) comprises an
AmoA protein having an identity to SEQ ID NO: 6 or 12 selected from
at least about 80%, 85%, 90%, 95%, 98%, 99%, 99.5%, and 100%
identical, an AmoB protein having an identity to SEQ ID NO: 8 or 14
selected from at least about 80%, 85%, 90%, 95%, 98%, 99%, 99.5%,
and 100% identical, an amoC gene having an identity to SEQ ID NO:
4, 10, or 16 selected from at least about 80%, 85%, 90%, 95%, 98%,
99%, 99.5%, and 100% identical, a hydroxylamine oxidoreductase
protein having an identity to SEQ ID NO: 18, 20, or 22 selected
from at least 80%, 85%, 90%, 95%, 98%, 99%, 99.5%, and 100%
identical, a cytochrome c554 protein having an identity to SEQ ID
NO: 24, 26, or 28 selected from at least about 80%, 85%, 90%, 95%,
98%, 99%, 99.5%, and 100% identical, or a cytochrome c.sub.M552
protein having an identity to SEQ ID NO: 30 or 32 selected from at
least about 80%, 85%, 90%, 95%, 98%, 99%, 99.5%, and 100%
identical.
[0016] In some embodiments, the purified preparation of optimized
N. eutropha bacterium (which is optionally axenic) comprises 1-5,
5-10, 10-15, 15-20, 20-25, 25-30, or all of the sequence
characteristics of Table 2. For instance, in some embodiments, the
bacterium or preparation comprises an AmoA1 or AmoA2 protein having
(or gene encoding) a mutation relative to N. eutropha strain C91 at
position 1, e.g., a V at position 1. In some embodiments, the
bacterium or preparation comprises an AmoA1 or AmoA2 protein having
(or gene encoding) a mutation relative to N. eutropha strain C91 at
position 160, e.g., an L at position 160. In some embodiments, the
bacterium or preparation comprises an AmoA1 or AmoA2 protein having
(or gene encoding) a mutation relative to N. eutropha strain C91 at
position 167, e.g., an A at position 167. In some embodiments, the
bacterium or preparation comprises an AmoB1 or AmoB2 protein having
(or gene encoding) a mutation relative to N. eutropha strain C91 at
position 33, e.g., a V at position 33. In some embodiments, the
bacterium or preparation comprises an AmoB1 or AmoB2 protein having
(or gene encoding) a mutation relative to N. eutropha strain C91 at
position 165, e.g., an I at position 165. In some embodiments, the
bacterium or preparation comprises an AmoC3 protein having (or gene
encoding) a mutation relative to N. eutropha strain C91 at position
79, e.g., an A at position 79. In some embodiments, the bacterium
or preparation comprises an AmoC3 protein having (or gene encoding)
a mutation relative to N. eutropha strain C91 at position 271,
e.g., a V at position 271. In some embodiments, the bacterium or
preparation comprises a Hao1, Hao2, or Hao3 protein having (or gene
encoding) a mutation relative to N. eutropha strain C91 at position
85, e.g., an S at position 85. In some embodiments, the bacterium
or preparation comprises a Hao1, Hao2, or Hao3 protein having (or
gene encoding) a mutation relative to N. eutropha strain C91 at
position 312, e.g., an E at position 312. In some embodiments, the
bacterium or preparation comprises a Hao1 protein having (or gene
encoding) a mutation relative to N. eutropha strain C91 at position
163, e.g., an A at position 163. In some embodiments, the bacterium
or preparation comprises a c554 CycA1, c554 CycA2, or c554 CycA3
protein having (or gene encoding) a mutation relative to N.
eutropha strain C91 at position 65, e.g., a T at position 65. In
some embodiments, the bacterium or preparation comprises a c554
CycA1 protein having (or gene encoding) a mutation relative to N.
eutropha strain C91 at position 186, e.g., a T at position 186. In
some embodiments, the bacterium or preparation comprises a
c.sub.M552 CycB1 or c.sub.M552 CycB2 protein having (or gene
encoding) a mutation relative to N. eutropha strain C91 at position
63, e.g., a V at position 63. In some embodiments, the bacterium or
preparation comprises a c.sub.M552 CycB1 or c.sub.M552 CycB2
protein having (or gene encoding) a mutation relative to N.
eutropha strain C91 at position 189, e.g., a P at position 189. In
some embodiments, the bacterium or preparation comprises a
c.sub.M552 CycB1 or c.sub.M552 CycB2 protein having (or gene
encoding) a mutation relative to N. eutropha strain C91 at position
206, e.g., an insE at position 206. In some embodiments, the
bacterium or preparation comprises a c.sub.M552 CycB1 or c.sub.M552
CycB2 protein having (or gene encoding) a mutation relative to N.
eutropha strain C91 at position 207, e.g., an insE at position 207.
In some embodiments, the bacterium or preparation comprises a
c.sub.M552 CycB1 protein having (or gene encoding) a mutation
relative to N. eutropha strain C91 at position 195, e.g., an insD
at position 195. In some embodiments, the bacterium or preparation
comprises a c.sub.M552 CycB1 protein having (or gene encoding) a
mutation relative to N. eutropha strain C91 at position 196, e.g.,
an insD at position 196. In some embodiments, the bacterium or
preparation comprises a c.sub.M552 CycB1 protein having (or gene
encoding) a mutation relative to N. eutropha strain C91 at position
197, e.g., an insD at position 197.
[0017] Combinations of two or more sequence characteristics of
Table 2 are also described. The two or more sequence
characteristics may be in the same gene or different genes. The two
or more sequence characteristics may be in the same protein or
different proteins. For instance, in some embodiments, the
bacterium or preparation comprises an AmoA1 or AmoA2 protein having
(or gene encoding) a mutation relative to N. eutropha strain C91 at
position 1, e.g., a V at position 1 and a mutation relative to N.
eutropha strain C91 at position 160, e.g., an L at position 160. In
some embodiments, the bacterium or preparation comprises an AmoA1
or AmoA2 protein having (or gene encoding) a mutation relative to
N. eutropha strain C91 at position 1, e.g., a V at position 1 and a
mutation relative to N. eutropha strain C91 at position 167, e.g.,
an A at position 167. In some embodiments, the bacterium or
preparation comprises an AmoA1 or AmoA2 protein having (or gene
encoding) a mutation relative to N. eutropha strain C91 at position
160, e.g., an L at position 160 and a mutation relative to N.
eutropha strain C91 at position 167, e.g., an A at position
167.
[0018] In some embodiments, the bacterium or preparation comprises
an AmoB1 or AmoB2 protein having (or gene encoding) a mutation
relative to N. eutropha strain C91 at position 33, e.g., a V at
position 33 and a mutation relative to N. eutropha strain C91 at
position 165, e.g., an I at position 165.
[0019] In some embodiments, the bacterium or preparation comprises
an AmoC3 protein having (or gene encoding) a mutation relative to
N. eutropha strain C91 at position 79, e.g., an A at position 79
and a mutation relative to N. eutropha strain C91 at position 271,
e.g., a V at position 271.
[0020] In some embodiments, the bacterium or preparation comprises
a Hao1, Hao2, or Hao3 protein having (or gene encoding) a mutation
relative to N. eutropha strain C91 at position 85, e.g., an S at
position 85 and a mutation relative to N. eutropha strain C91 at
position 312, e.g., an E at position 312. In some embodiments, the
bacterium or preparation comprises a Hao1 protein having (or gene
encoding) a mutation relative to N. eutropha strain C91 at position
85, e.g., an S at position 85 and a mutation relative to N.
eutropha strain C91 at position 163, e.g., an A at position 163. In
some embodiments, the bacterium or preparation comprises a Hao1
protein having (or gene encoding) a mutation relative to N.
eutropha strain C91 at position 312, e.g., an E at position 312 and
a mutation relative to N. eutropha strain C91 at position 163,
e.g., an A at position 163.
[0021] In some embodiments, the bacterium or preparation comprises
a c554 CycA1 protein having (or gene encoding) a mutation relative
to N. eutropha strain C91 at position 65, e.g., a T at position 65
and a mutation relative to N. eutropha strain C91 at position 186,
e.g., a T at position 186.
[0022] In some embodiments, the bacterium or preparation comprises
a c.sub.M552 CycB1 protein having (or gene encoding) mutations at
any two or more of the following amino acid positions: 63, 189,
194, 195, 196, 197, 206, and 207. For instance, the two or more
amino acid positions may comprise: 63 and 189, 63 and 194, 63 and
195, 63 and 196, 63 and 197, 63 and 206, 63 and 207, 189 and 194,
189 and 195, 189 and 196, 189 and 194, 189 and 195, 189 and 196,
189 and 197, 189 and 206, 189 and 207, 194 and 195, 194 and 196,
194 and 197, 194 and 206, 194 and 207, 195 and 196, 195 and 197,
195 and 206, 195 and 207, 196 and 197, 196 and 206, 196 and 207,
197 and 206, 197 and 207, or 206 and 207. In some embodiments, the
bacterium or preparation comprises a c.sub.M552 CycB1 protein
having (or gene encoding) any two or more mutations selected from
the group consisting of: I63V, S189P, D194G, 195insD, 196insD,
197insD, 206insE, and 207insE. For instance, the two or more
mutations can be selected from the group consisting of: I63V and
S189P, I63V and D194G, I63V and 195insD, I63V and 196insD, I63V and
197insD, I63V and 206insE, I63V and 207insE, S189P and D194G, S189P
and 195insD, S189P and 196insD, S189P and 197insD, S189P and
206insE, S189P and 207insE, D194G and 195insD, D194G and 196insD,
D194G and 197insD, D194G and 206insE, D194G and 207insE, 195insD
and 196insD, 195insD and 197insD, 195insD and 206insE, 195insD and
207insE, 196insD and 197insD, 196insD and 206insE, 196insD and
207insE, 197insD and 206insE, 197insD and 207insE, and 206insE and
207insE.
[0023] In some embodiments, the bacterium or preparation comprises
a c.sub.M552 CycB2 protein having (or gene encoding) mutations at
any two or more of the following amino acid positions: 63, 189,
206, and 207. For instance, the two or more amino acid positions
may comprise: 63 and 189, 63 and 206, 63 and 207, 189 and 206, 189
and 207, or 206 and 207. In some embodiments, the bacterium or
preparation comprises a c.sub.M552 CycB2 protein having (or gene
encoding) any two or more mutations selected from the group
consisting of: I63V, S189P, 206insE, and 207insE. For instance, the
two or more mutations can be selected from the group consisting of:
I63V and S189P, I63V and 206insE, I63V and 207insE, S189P and
206insE, S189P and 207insE, and 206insE and 207insE.
[0024] Combinations of three or more sequence characteristics of
Table 2 are also described. For instance, in some embodiments, the
bacterium or preparation comprises an AmoA1 or AmoA2 protein having
(or gene encoding) a mutation relative to N. eutropha strain C91 at
position 1, e.g., a V at position 1 and a mutation relative to N.
eutropha strain C91 at position 160, e.g., an L at position 160,
and a mutation relative to N. eutropha strain C91 at position 167,
e.g., an A at position 167.
[0025] In some embodiments, the bacterium or preparation comprises
a Hao1 protein having (or gene encoding) a mutation relative to N.
eutropha strain C91 at position 85, e.g., an S at position 85 and a
mutation relative to N. eutropha strain C91 at position 312, e.g.,
an E at position 312, and a mutation relative to N. eutropha strain
C91 at position 163, e.g., an A at position 163.
[0026] In some embodiments, the bacterium or preparation comprises
a c.sub.M552 CycB1 protein having (or gene encoding) mutations at
any three or more (e.g., 4, 5, 6, 7, or all) of the following amino
acid positions: 63, 189, 194, 195, 196, 197, 206, and 207. For
instance, the three mutations may be at positions 195, 196, and
197. In some embodiments, the bacterium or preparation comprises a
c.sub.M552 CycB1 protein having (or gene encoding) any three or
more (e.g., 4, 5, 6, 7, or all) mutations selected from the group
consisting of: I63V, S189P, D194G, 195insD, 196insD, 197insD,
206insE, and 207insE. For instance, the three mutations may be
195insD, 196insD, and 197insD.
[0027] In some embodiments, the bacterium or preparation comprises
a c.sub.M552 CycB2 protein having (or gene encoding) mutations at
any three or more (e.g., all) of the following amino acid
positions: 63, 189, 206, and 207. In some embodiments, the
bacterium or preparation comprises a c.sub.M552 CycB2 protein
having (or gene encoding) any three or more (e.g., all) mutations
selected from the group consisting of: I63V, S189P, 206insE, and
207insE.
[0028] In some embodiments, the bacterium or preparation comprises
mutations relative to N. eutropha strain C91 in at least two genes,
e.g., at least two genes listed in Table 2. The two genes may be,
for instance, AmoA1 and AmoA2, AmoA1 and AmoB1, AmoA1 and AmoB2,
AmoA1 and AmoC1, AmoA1 and AmoC2, AmoA1 and AmoC3, AmoA1 and Hao1,
AmoA1 and Hao2, AmoA1 and Hao3, AmoA1 and c554 CycA1, AmoA1 and
c554 CycA2, AmoA1 and c554 CycA3, AmoA1 and cM552 CycB1, AmoA1 and
cM552 CycB2, AmoA2 and AmoB1, AmoA2 and AmoB2, AmoA2 and AmoC1,
AmoA2 and AmoC2, AmoA2 and AmoC3, AmoA2 and Hao1, AmoA2 and Hao2,
AmoA2 and Hao3, AmoA2 and c554 CycA1, AmoA2 and c554 CycA2, AmoA2
and c554 CycA3, AmoA2 and cM552 CycB1, AmoA2 and cM552 CycB2, AmoB1
and AmoB2, AmoB1 and AmoC1, AmoB1 and AmoC2, AmoB1 and AmoC3, AmoB1
and Hao1, AmoB1 and Hao2, AmoB1 and Hao3, AmoB1 and c554 CycA1,
AmoB1 and c554 CycA2, AmoB1 and c554 CycA3, AmoB1 and cM552 CycB1,
AmoB1 and cM552 CycB2, AmoB2 and AmoC1, AmoB2 and AmoC2, AmoB2 and
AmoC3, AmoB2 and Hao1, AmoB2 and Hao2, AmoB2 and Hao3, AmoB2 and
c554 CycA1, AmoB2 and c554 CycA2, AmoB2 and c554 CycA3, AmoB2 and
cM552 CycB1, AmoB2 and cM552 CycB2, AmoC1 and AmoC2, AmoC1 and
AmoC3, AmoC1 and Hao1, AmoC1 and Hao2, AmoC1 and Hao3, AmoC1 and
c554 CycA1, AmoC1 and c554 CycA2, AmoC1 and c554 CycA3, AmoC1 and
cM552 CycB1, AmoC1 and cM552 CycB2, AmoC2 and AmoC3, AmoC2 and
Hao1, AmoC2 and Hao2, AmoC2 and Hao3, AmoC2 and c554 CycA1, AmoC2
and c554 CycA2, AmoC2 and c554 CycA3, AmoC2 and cM552 CycB1, AmoC2
and cM552 CycB2, AmoC3 and Hao1, AmoC3 and Hao2, AmoC3 and Hao3,
AmoC3 and c554 CycA1, AmoC3 and c554 CycA2, AmoC3 and c554 CycA3,
AmoC3 and cM552 CycB1, AmoC3 and cM552 CycB2, Hao1 and Hao2, Hao1
and Hao3, Hao1 and c554 CycA1, Hao1 and c554 CycA2, Hao1 and c554
CycA3, Hao1 and cM552 CycB1, Hao1 and cM552 CycB2, Hao2 and Hao3,
Hao2 and c554 CycA1, Hao2 and c554 CycA2, Hao2 and c554 CycA3, Hao2
and cM552 CycB1, Hao2 and cM552 CycB2, Hao3 and c554 CycA1, Hao3
and c554 CycA2, Hao3 and c554 CycA3, Hao3 and cM552 CycB1, Hao3 and
cM552 CycB2, c554 CycA1 and c554 CycA2, c554 CycA1 and c554 CycA3,
c554 CycA1 and cM552 CycB1, c554 CycA1 and cM552 CycB2, c554 CycA2
and c554 CycA3, c554 CycA2 and cM552 CycB1, c554 CycA2 and cM552
CycB2, c554 CycA3 and cM552 CycB1, c554 CycA3 and cM552 CycB2, or
cM552 CycB1 and cM552 CycB2.
[0029] In some embodiments, the bacterium or preparation comprises
mutations relative to N. eutropha strain C91 in at least three
genes, e.g., at least three (e.g., 4, 5, 6, 7, 8, 9, 10, 11, 12,
13, 14, or all) genes listed in Table 2. The three genes may be,
for instance AmoA1 and AmoA2 and AmoA3; AmoC1 and AmoC2 and AmoC3;
or Hao1 and Hao2 and Hao3.
[0030] In some embodiments, the bacterium or preparation comprises
at least one structural difference, e.g., at least one mutation,
relative to a wild-type bacterium such as N. eutropha strain C91.
In some embodiments, the bacterium or preparation comprises a
nucleic acid that can be amplified using a pair of primers
described herein, e.g., a primer comprising a sequence of SEQ ID
NO: 64 and a primer comprising a sequence of SEQ ID NO: 65. In some
embodiments, the bacterium or preparation comprises a nucleic acid
or protein at least 80%, 85%, 90%, 95%, 98%, 99%, 99.5%, or 100%
identical to a gene of FIG. 6, 7, or 8, or a protein encoded by a
gene of FIG. 6, 7, or 8. In some embodiments, the bacterium or
preparation comprises a nucleic acid or protein at least 80%, 85%,
90%, 95%, 98%, 99%, 99.5%, or 100% identical to a sequence of any
of SEQ ID NOS: 64-66 or a protein encoded by a sequence of any of
SEQ ID NOS: 64-66.
[0031] In some aspects, the present disclosure provides, inter
alia, an N. eutropha bacterium, or a purified preparation thereof,
comprising a mutation in an ammonia monooxygenase gene, a
hydroxylamine oxidoreductase gene, a cytochrome c554 gene, or a
cytochrome c.sub.M552 gene. The mutation may be relative to a
wild-type bacterium such as N. eutropha strain C91. The mutation
may be in one or more of the amoA1 gene, the amoA2 gene, amoB1
gene, the amoB2 gene, and the amoC3 gene. The N. eutropha
bacterium, or a purified preparation thereof may have a mutation at
a position described herein, e.g., in Table 2. The N. eutropha
bacterium, or a purified preparation thereof may have a mutation
wherein said mutation is a mutation described herein, e.g., in
Table 2.
[0032] In some embodiments, the mutation may be in one or more of
the hao1 gene, the hao2 gene, or the hao3 gene. The N. eutropha
bacterium, or a purified preparation thereof may have a mutation at
a position described herein, e.g., in Table 2. The N. eutropha
bacterium, or a purified preparation thereof may have a mutation
wherein said mutation is a mutation described herein, e.g., in
Table 2.
[0033] In some embodiments, the mutation may be in one or more of
the c554 cycA1 gene, the c554 cycA2 gene, and the c554 cycA3 gene.
The N. eutropha bacterium, or a purified preparation thereof may
have a mutation at a position described herein, e.g., in Table 2.
The N. eutropha bacterium, or a purified preparation thereof may
have a mutation wherein said mutation is a mutation described
herein, e.g., in Table 2.
[0034] In some embodiments, the mutation may be in one or more of
the c.sub.M552 cycB1 gene and the c.sub.M552 cycB2 gene. The N.
eutropha bacterium, or a purified preparation thereof may have a
mutation at a position described herein, e.g., in Table 2. The N.
eutropha bacterium, or a purified preparation thereof may have a
mutation wherein said mutation is a mutation described herein,
e.g., in Table 2.
[0035] In certain aspects the N. eutropha bacterium, or a purified
preparation thereof, described in the preceding four paragraphs may
be based on a N. eutropha bacterium, e.g., an optimized N.
eutropha, e.g., a purified preparation of optimized N. eutropha,
having at least one property selected from: [0036] an optimized
growth rate; [0037] an optimized NH.sub.4.sup.+ oxidation rate; and
[0038] an optimized resistance to ammonium ion
(NH.sub.4.sup.+).
[0039] In certain aspects, the N. eutropha bacterium, or a purified
preparation thereof, described in the preceding five paragraphs may
have a mutation in at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13,
14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30,
31, 32, 33, 34, or 35 positions of one or more of amoA1 gene, amoA2
gene, amoB1 gene, amoB2 gene, amoC3 gene, hao1 gene, hao2 gene,
hao3 gene, c554 cycA1 gene, c554 cycA2 gene, c554 cycA3 gene,
c.sub.M552 cycB1 gene, and c554 cycB2 gene.
[0040] In some embodiments, the N. eutropha bacterium has an
optimized growth rate, e.g., an optimized growth rate described
herein, and a structural difference such as a mutation (e.g.,
relative to a wild-type strain such as N. eutropha strain C91),
e.g., a mutation described herein, e.g., a mutation of Table 2. In
some embodiments, the N. eutropha bacterium has an optimized
NH.sub.4.sup.+ oxidation rate, e.g., an optimized NH.sub.4.sup.+
oxidation rate described herein, and a structural difference such
as a mutation (e.g., relative to a wild-type strain such as N.
eutropha strain C91), e.g., a mutation described herein, e.g., a
mutation of Table 2. In some embodiments, the N. eutropha bacterium
has an optimized resistance to NH.sub.4.sup.+, e.g., an optimized
resistance to NH.sub.4.sup.+ described herein, and a structural
difference such as a mutation (e.g., relative to a wild-type strain
such as N. eutropha strain C91), e.g., a mutation described herein,
e.g., a mutation of Table 2.
[0041] In some embodiments, the N. eutropha bacterium comprises a
nucleic acid that can be amplified using a pair of primers
described herein, e.g., a primer comprising a sequence of SEQ ID
NO: 64 and a primer comprising a sequence of SEQ ID NO: 65.
[0042] In certain aspects, this disclosure provides an N. eutropha
bacterium (which is optionally axenic) comprising a chromosome that
hybridizes at high stringency to SEQ ID NO: 1.
[0043] In embodiments, the chromosome hybridizes at very high
stringency to SEQ ID NO: 1. In embodiments, the N. eutropha
bacterium (which is optionally axenic) comprises a gene that is at
least about 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% identical to
one or more genes of FIGS. 6-8 (e.g., 10, 20, 30, 40, 50, 100, or
all genes of any one or more of FIGS. 6, 7, and 8).
[0044] In embodiments, the N. eutropha bacterium (which is
optionally axenic) lacks any plasmid that is at least about 80%,
85%, 90%, 95%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 2
(pNeut1) or SEQ ID NO: 3 (pNeut2), as described by Stein et al.
Whole-genome analysis of the ammonia-oxidizing bacterium,
Nitrosomonas eutropha C91: implications for niche adaptation.
Environmental Microbiology (2007) 9(12), 2993-3007. In embodiments,
the N. eutropha (which is optionally axenic) lacks one or more
genes present on the plasmids of SEQ ID NO: 2 or SEQ ID NO: 3. For
instance, the N. eutropha (which is optionally axenic) may lack at
least 2, 3, 4, 5, 10, 15, or 20 genes present on one or both of
pNeut1 and pNeut2. pNeut1 contains 55 protein-coding sequences
while pNeutP2 contains 52 protein-coding sequences. In embodiments,
the N. eutropha bacterium (which is optionally axenic) lacks any
plasmid.
[0045] In certain aspects, this disclosure provides an N. eutropha
bacterium (which is optionally axenic) comprising one or more of an
amoA1 gene at least about 98.9% identical to SEQ ID NO: 7 and an
amoA2 gene at least about 98.8% identical to SEQ ID NO: 13.
[0046] In certain aspects, this disclosure provides an N. eutropha
bacterium (which is optionally axenic) comprising one or more of an
AmoA1 protein at least about 99.0% identical to SEQ ID NO: 6 and an
AmoA2 protein at least about 99.0% identical to SEQ ID NO: 12.
[0047] In certain aspects, this disclosure provides an N. eutropha
bacterium (which is optionally axenic) comprising one or more of an
amoB1 gene at least about 99.2% identical to SEQ ID NO: 9 and an
amoB2 gene at least about 99.2% identical to SEQ ID NO: 15.
[0048] In embodiments, the N. eutropha bacterium (which is
optionally axenic) further comprises one or more of an amoA1 or
amoA2 gene at least about 98.9% identical to SEQ ID NO: 7 or
13.
[0049] In certain aspects, this disclosure provides an N. eutropha
bacterium (which is optionally axenic) comprising one or more of an
AmoB1 protein at least about 99.6% identical to SEQ ID NO: 8 and an
AmoB1 protein at least about 99.6% identical to SEQ ID NO: 14.
[0050] In embodiments, the N. eutropha bacterium (which is
optionally axenic) further comprises one or more of an AmoA1
protein at least about 99.0% identical to SEQ ID NO: 6 and an AmoA2
protein at least about 99.0% identical to SEQ ID NO: 12.
[0051] In certain aspects, this disclosure provides an N. eutropha
bacterium (which is optionally axenic) comprising one or more of an
amoC1 gene at least about 99.9% identical to SEQ ID NO: 5, an amoC2
gene at least about 99.9% identical to SEQ ID NO: 11, and an amoC3
gene at least about 99.0% identical to SEQ ID NO: 17.
[0052] In embodiments, the N. eutropha bacterium (which is
optionally axenic) further comprises one or more of an amoA1 gene
at least about 98.9% identical to SEQ ID NO: 7, an amo2 gene at
least about 98.9% identical to SEQ ID NO: 13, an amoB1 gene at
least about 99.2% identical to SEQ ID NO: 9, and an amoB2 gene at
least about 99.2% identical to SEQ ID NO: 15.
[0053] In certain aspects, this disclosure provides an N. eutropha
bacterium (which is optionally axenic) comprising an AmoC3 protein
at least about 99.4% identical to SEQ ID NO: 16.
[0054] In embodiments, the N. eutropha bacterium (which is
optionally axenic) further comprises one or more of an AmoA1
protein at least about 99.0% identical to SEQ ID NO: 6, an AmoA2
protein at least about 99.0% identical to SEQ ID NO: 12, an AmoB1
protein at least about 99.6% identical to SEQ ID NO: 8, and an
AmoB1 protein at least about 99.6% identical to SEQ ID NO: 14.
[0055] In certain aspects, this disclosure provides an N. eutropha
bacterium (which is optionally axenic) comprising one or more of a
hao1 gene at least about 99.1% identical to SEQ ID NO: 19, a hao2
gene at least about 99.5% identical to SEQ ID NO: 21, and a hao3
gene at least about 99.3% identical to SEQ ID NO: 23.
[0056] In embodiments, the N. eutropha bacterium (which is
optionally axenic) further comprises one or more of an amoA1 gene
at least about 98.9% identical to SEQ ID NO: 7, an amo2 gene at
least about 98.9% identical to SEQ ID NO: 13, an amoB1 gene at
least about 99.2% identical to SEQ ID NO: 9, an amoB2 gene at least
about 99.2% identical to SEQ ID NO: 15, an amoC1 gene at least
about 99.9% identical to SEQ ID NO: 5, an amoC2 gene at least about
99.9% identical to SEQ ID NO: 11, and an amoC3 gene at least about
99.0% identical to SEQ ID NO: 17.
[0057] In certain aspects, this disclosure provides an N. eutropha
bacterium (which is optionally axenic) comprising one or more of a
Hao1 protein at least about 99.6% identical to SEQ ID NO: 18, a
Hao2 protein at least about 99.7% identical to SEQ ID NO: 20, and a
Hao3 protein at least about 99.7% identical to SEQ ID NO: 22.
[0058] In embodiments, the N. eutropha bacterium (which is
optionally axenic) further comprises an AmoA1 protein at least
about 99.0% identical to SEQ ID NO: 6, an AmoA2 protein at least
about 99.0% identical to SEQ ID NO: 12, an AmoB1 protein at least
about 99.6% identical to SEQ ID NO: 8, an AmoB1 protein at least
about 99.6% identical to SEQ ID NO: 14, or an AmoC3 protein at
least about 99.4% identical to SEQ ID NO: 16.
[0059] In certain aspects, this disclosure provides an N. eutropha
bacterium (which is optionally axenic) comprising one or more of a
cycA1 gene at least about 98.1% identical to SEQ ID NO: 25, a cycA2
gene at least about 98.8% identical to SEQ ID NO: 27, and a cycA3
gene at least about 99.4% identical to SEQ ID NO: 28.
[0060] In embodiments, the N. eutropha bacterium (which is
optionally axenic) further comprises one or more of an amoA1 gene
at least about 98.9% identical to SEQ ID NO: 7, an amo2 gene at
least about 98.9% identical to SEQ ID NO: 13, an amoB1 gene at
least about 99.2% identical to SEQ ID NO: 9, an amoB2 gene at least
about 99.2% identical to SEQ ID NO: 15, an amoC1 gene at least
about 99.9% identical to SEEQ ID NO: 5, an amoC2 gene at least
about 99.9% identical to SEQ ID NO: 11, an amoC3 gene at least
about 99.0% identical to SEQ ID NO: 17, a hao1 gene at least about
99.1% identical to SEQ ID NO: 19, a hao2 gene at least about 99.5%
identical to SEQ ID NO: 21, and a hao3 gene at least about 99.3%
identical to SEQ ID NO: 23.
[0061] In certain aspects, this disclosure provides an N. eutropha
bacterium (which is optionally axenic) comprising one or more of a
CycA1 protein at least about 99.2% identical to SEQ ID NO: 24, a
CycA2 protein at least about 99.7% identical to SEQ ID NO: 26, and
a CycA3 protein at least about 99.7% identical to SEQ ID NO:
28.
[0062] In embodiments, the N. eutropha bacterium (which is
optionally axenic) further comprises one or more of an AmoA1
protein at least about 99.0% identical to SEQ ID NO: 6, an AmoA2
protein at least about 99.0% identical to SEQ ID NO: 12, an AmoB1
protein at least about 99.6% identical to SEQ ID NO: 8, an AmoB1
protein at least about 99.6% identical to SEQ ID NO: 14, an AmoC3
protein at least about 99.4% identical to SEQ ID NO: 16, a Hao1
protein at least about 99.6% identical to SEQ ID NO: 18, a Hao2
protein at least about 99.7% identical to SEQ ID NO: 20, and a Hao3
protein at least about 99.7% identical to SEQ ID NO: 22.
[0063] In certain aspects, this disclosure provides an N. eutropha
bacterium (which is optionally axenic) comprising one or more of a
cycB1 gene at least about 96.8% identical to SEQ ID NO: 31 and a
cycB2 gene at least about 97.2% identical to SEQ ID NO: 33.
[0064] In embodiments, the N. eutropha bacterium (which is
optionally axenic) further comprises one or more of an amoA1 gene
at least about 98.9% identical to SEQ ID NO: 7, an amo2 gene at
least about 98.9% identical to SEQ ID NO: 13, an amoB1 gene at
least about 99.2% identical to SEQ ID NO: 9, an amoB2 gene at least
about 99.2% identical to SEQ ID NO: 15, an amoC1 gene at least
about 99.9% identical to SEQ ID NO: 5, an amoC2 gene at least about
99.9% identical to SEQ ID NO: 11, an amoC3 gene at least about
99.0% identical to SEQ ID NO: 17, a hao1 gene at least about 99.1%
identical to SEQ ID NO: 19, a hao2 gene at least about 99.5%
identical to SEQ ID NO: 21, a hao3 gene at least about 99.3%
identical to SEQ ID NO: 23, a cycA1 gene at least about 98.1%
identical to SEQ ID NO: 25, a cycA2 gene at least about 98.8%
identical to SEQ ID NO: 27, and a cycA3 gene at least about 99.4%
identical to SEQ ID NO: 28.
[0065] In certain aspects, this disclosure provides an N. eutropha
bacterium (which is optionally axenic) comprising one or more of a
CycB1 protein at least about 97.2% identical to SEQ ID NO: 30 or a
CycB2 protein at least about 98.8% identical to SEQ ID NO: 32.
[0066] In embodiments, the N. eutropha bacterium (which is
optionally axenic) further comprises one or more of an AmoA1
protein at least about 99.0% identical to SEQ ID NO: 6, an AmoA2
protein at least about 99.0% identical to SEQ ID NO: 12, an AmoB1
protein at least about 99.6% identical to SEQ ID NO: 8, an AmoB1
protein at least about 99.6% identical to SEQ ID NO: 14, an AmoC3
protein at least about 99.4% identical to SEQ ID NO: 16, a Hao1
protein at least about 99.6% identical to SEQ ID NO: 18, a Hao2
protein at least about 99.7% identical to SEQ ID NO: 20, a Hao3
protein at least about 99.7% identical to SEQ ID NO: 22, a CycA1
protein at least about 99.2% identical to SEQ ID NO: 24, a CycA2
protein at least about 99.7% identical to SEQ ID NO: 26, and a
CycA3 protein at least about 99.7% identical to SEQ ID NO: 28.
[0067] In certain aspects, this disclosure provides an N. eutropha
bacterium (which is optionally axenic) comprising one or more genes
according to SEQ ID NOS: 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25,
27, 29, 31, and 33.
[0068] In certain aspects, this disclosure provides an N. eutropha
bacterium (which is optionally axenic) comprising one or more
proteins according to SEQ ID NOS: 4, 6, 8, 10, 12, 14, 16, 18, 20,
22, 24, 26, 28, 30, and 32.
[0069] In certain aspects, this disclosure provides an N. eutropha
bacterium (which is optionally axenic) comprising a protein that is
mutant relative to N. eutropha strain C91 at at least 1, 2, 3, 4,
5, 10, 15, 20, 25, 30, or all of the amino acid positions listed in
Table 2.
[0070] In certain aspects, this disclosure provides an N. eutropha
bacterium (which is optionally axenic) comprising proteins that are
mutant relative to N. eutropha strain C91 at all of the amino acid
positions listed in Table 2.
[0071] In certain aspects, this disclosure provides an N. eutropha
bacterium (which is optionally axenic) of strain D23, 25 vials of
said bacterium, designated AOB D23-100, having been deposited with
the ATCC patent depository on Apr. 8, 2014 under ATCC accession
number PTA-121157.
[0072] In embodiments, the N. eutropha bacterium (which is
optionally axenic) is transgenic.
[0073] In embodiments, the N. eutropha bacterium (which is
optionally axenic) has at least one property selected from an
optimized growth rate, an optimized NH.sub.4.sup.+ oxidation rate,
and an optimized resistance to NH.sub.4.sup.+.
[0074] In embodiments, the N. eutropha bacterium (which is
optionally axenic) has at least two properties selected from an
optimized growth rate, an optimized NH.sub.4.sup.+ oxidation rate,
and an optimized resistance to NH.sub.4.sup.+.
[0075] In embodiments, the N. eutropha bacterium (which is
optionally axenic) has an optimized growth rate, an optimized
NH.sub.4.sup.+ oxidation rate, and an optimized resistance to
NH.sub.4.sup.+.
[0076] In embodiments, the N. eutropha bacterium as described
herein (e.g., strain D23) is substantially free of bacteria, other
ammonia oxidizing bacteria, fungi, viruses, or pathogens (e.g.,
animal pathogens, e.g., human pathogens), or any combination
thereof.
[0077] In certain aspects, this disclosure provides a composition
comprising the N. eutropha bacterium as described herein (e.g.,
strain D23), wherein the composition is substantially free of other
organisms.
[0078] In certain aspects, this disclosure provides a composition
comprising the N. eutropha bacterium as described herein (e.g.,
strain D23) and further comprising a second organism (e.g., a
second strain or species), wherein the composition is substantially
free of other organisms (e.g., strains or species). In embodiments,
the second organism is an ammonia oxidizing bacterium. In
embodiments, the second organism is selected from the group
consisting of Nitrosomonas, Nitrosococcus, Nitrosospria,
Nitrosocystis, Nitrosolobus, Nitrosovibrio, Lactobacillus,
Streptococcus, and Bifidobacter, and combinations thereof.
[0079] This disclosure also provides a composition comprising the
N. eutropha bacterium as described herein (e.g., strain D23) and
further comprising a second and a third organism (e.g., of other
strains or species), wherein the composition is substantially free
of other organisms (e.g., strains or species). This disclosure also
provides a composition comprising the N. eutropha bacterium as
described herein (e.g., strain D23) and further comprising 2, 3, 4,
5, 6, 7, 8, 9, or 10 other organisms (e.g., of other strains or
species), wherein the composition is substantially free of other
organisms (e.g., strains or species).
[0080] In some aspects, this disclosure provides a composition
comprising a cell suspension of an actively dividing culture of N.
eutropha bacteria having an OD600 of at least about 0.1, 0.15, 0.2,
0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.6, 0.7, or 0.8, wherein the
composition is substantially free of other organisms.
[0081] In some aspects, this disclosure provides a composition for
topical administration, comprising the N. eutropha bacterium as
described herein (e.g., strain D23) and a pharmaceutically or
cosmetically acceptable excipient suitable for topical
administration. In embodiments, the composition is substantially
free of other organisms. In embodiments, the composition further
comprises a second organism (e.g., of another strain or specie). In
embodiments, the composition further comprises 2, 3, 4, 5, 6, 7, 8,
9, or 10 other organisms (e.g., of other strains or species). The
second organism may be, for example, an ammonia oxidizing
bacterium. In embodiments, the second organism is selected from the
group consisting of Nitrosomonas, Nitrosococcus, Nitrosospria,
Nitrosocystis, Nitrosolobus, Nitrosovibrio, Lactobacillus,
Streptococcus, and Bifidobacter, and combinations thereof.
[0082] In embodiments, the composition is a powder, cosmetic,
cream, stick, aerosol, salve, wipe, or bandage. In embodiments, the
composition further comprises a moisturizing agent, deodorizing
agent, scent, colorant, insect repellant, cleansing agent, or
UV-blocking agent. In embodiments, the excipient is an
anti-adherent, binder, coat, disintegrant, filler, flavor, color,
lubricant, glidant, sorbent, preservative, or sweetener. In
embodiments, the concentration of N. eutropha in the composition is
about 10.sup.11-10.sup.13 CFU/L. In embodiments, the concentration
of N. eutropha in the composition is about 10.sup.9 CFU/ml. In
embodiments, the mass ratio of N. eutropha to pharmaceutical
excipient may be about 0.1 gram per liter to about 100 grams per
liter. In some embodiments, the mass ratio of N. eutropha to
pharmaceutical excipient is 1 gram per liter.
[0083] In some aspects the composition and/or excipient may be in
the form of one or more of a liquid, a solid, or a gel. For
example, liquid suspensions may include, but are not limited to,
water, saline, phosphate-buffered saline, or an ammonia oxidizing
storage buffer. Gel formulations may include, but are not limited
to agar, silica, polyacrylic acid (for example Carbopol.RTM.),
carboxymethyl cellulose, starch, guar gum, alginate or chitosan. In
some embodiments, the formulation may be supplemented with an
ammonia source including, but not limited to ammonium chloride or
ammonium sulfate.
In some aspects, this disclosure provides a composition comprising
at least about 10, 20, 50, 100, 200, 500, 1,000, 2,000, or 10,000
L, e.g., at about 10.sup.11 CFU/L, 10.sup.12 CFU/L, 10.sup.13 CFU/L
of the N. eutropha bacterium as described herein (e.g., strain
D23). In some embodiments, the composition is at a concentration of
at least about 10.sup.9 CFU/L, 10.sup.10 CFU/L, 10.sup.11 CFU/L, or
10.sup.12 CFU/L. In some aspects, this disclosure provides a
composition comprising at least about 1, 2, 5, 10, 20, 50, 100,
200, or 500 g of the N. eutropha bacterium described herein, e.g.,
as a dry formulation such as a powder.
[0084] In some aspects, this disclosure provides an article of
clothing comprising the N. eutropha as described herein (e.g.,
strain D23). In embodiments, the article of clothing is packaged.
In embodiments, the article of clothing is packaged in a material
that is resistant to gaseous exchange or resistant to water. The
article of clothing may be provided, e.g., at a concentration that
provides one or more of a treatment or prevention of a skin
disorder, a treatment or prevention of a disease or condition
associated with low nitrite levels, a treatment or prevention of
body odor, a treatment to supply nitric oxide to a subject, or a
treatment to inhibit microbial growth.
[0085] In some aspects, this disclosure provides a cloth comprising
the N. eutropha as described herein (e.g., strain D23).
[0086] In some aspects, this disclosure provides a yarn comprising
the N. eutropha as described herein (e.g., strain D23).
[0087] In some aspects, this disclosure provides a thread
comprising the N. eutropha as described herein (e.g., strain
D23).
[0088] In some aspects, this disclosure provides a method of
obtaining, e.g., manufacturing, an (optionally axenic) N. eutropha
bacterium having an optimized growth rate, an optimized
NH.sub.4.sup.+ oxidation rate, or an optimized resistance to
NH.sub.4.sup.+, comprising:
[0089] (a) culturing the bacterium under conditions that select for
one or more of an optimized growth rate, an optimized
NH.sub.4.sup.+ oxidation rate, or an optimized resistance to
NH.sub.4.sup.+, thereby producing a culture;
[0090] (b) testing a sample from the culture for an optimized
growth rate, an optimized NH.sub.4.sup.+ oxidation rate, or an
optimized resistance to NH.sub.4.sup.+; and
[0091] (c) repeating the culturing and testing steps until a
bacterium having an optimized growth rate, an optimized
NH.sub.4.sup.+ oxidation rate, or an optimized resistance to
NH.sub.4.sup.+ is obtained.
[0092] In embodiments, the method comprises a step of obtaining an
N. eutropha bacterium from a source, such as soil or the skin of an
individual. In embodiments, culturing the bacterium under
conditions that select for one or more (e.g., 2 or 3) of an
optimized growth rate, an optimized NH.sub.4.sup.+ oxidation rate,
or an optimized resistance to NH.sub.4.sup.+ comprises culturing
the bacterium in N. europaea medium that comprises about 200 mM
NH.sub.4.sup.+. In embodiments, the method comprises a step of
creating an axenic culture. In embodiments, the method comprises a
step of co-culturing the N. eutropha together with at least one
other type of ammonia oxidizing bacteria. In embodiments, the N.
eutropha of step (a) lack an optimized growth rate, an optimized
NH.sub.4.sup.+ oxidation rate, and an optimized resistance to
NH.sub.4.sup.+ In embodiments, step (c) comprises repeating the
culturing and testing steps until a bacterium having at least two
of an optimized growth rate, an optimized NH.sub.4.sup.+ oxidation
rate, and an optimized resistance to NH.sub.4.sup.+ is
obtained.
[0093] In some aspects, this disclosure provides an N. eutropha
bacterium as described herein (e.g., strain D23), produced by the
methods described above.
[0094] In some aspects, this disclosure provides a method of
testing a preparation of (optionally axenic) N. eutropha,
comprising:
[0095] assaying the N. eutropha for one or more of an optimized
growth rate, an optimized NH.sub.4.sup.+ oxidation rate, or an
optimized resistance to NH.sub.4.sup.+; and
[0096] if the N. eutropha has one or more of an optimized growth
rate, an optimized NH.sub.4.sup.+ oxidation rate, or an optimized
resistance to NH.sub.4.sup.+, classifying the N. eutropha as
accepted.
[0097] In embodiments, the method further comprises a step of
testing the preparation for contaminating organisms. In
embodiments, the method further comprises a step of removing a
sample from the preparation and conducting testing on the sample.
In embodiments, the method further comprises testing medium in
which the N. eutropha is cultured. In embodiments, the method
further comprises packaging N. eutropha from the preparation into a
package. In embodiments, the method further comprises placing N.
eutropha from the preparation into commerce.
[0098] In some aspects, this disclosure provides a method of
producing, e.g., manufacturing N. eutropha, comprising contacting
N. eutropha with culture medium and culturing the N. eutropha until
an OD600 of at least about 0.3, 0.4, 0.5, 0.6, 0.7, or 0.8 is
reached. In some embodiments, the method comprises culturing the N.
eutropha until an OD600 of at about 0.3-0.4, 0.4-0.5, 0.5-0.6,
0.6-0.7, or 0.7-0.8 is reached.
[0099] In embodiments, the method further comprises assaying the N.
eutropha and culture medium for contaminating organisms. In
embodiments, the method further comprises assaying the N. eutropha
for one or more (e.g., 2 or 3) of an optimized growth rate, an
optimized NH.sub.4.sup.+ oxidation rate, or an optimized resistance
to NH.sub.4.sup.+ In embodiments, the method comprises producing at
least at least about 10, 20, 50, 100, 200, 500, 1,000, 2,000,
5,000, or 10,000 L per day of N. eutropha, e.g., at about 10.sup.12
CFUs/L. In some embodiments, the N. eutropha is at a concentration
of about 10.sup.9, 10.sup.10, 10.sup.11, 10.sup.12, 10.sup.13, or
10.sup.14 CFUs/L. In some embodiments, the N. eutropha is at a
concentration of least about 10.sup.9, 10.sup.10, 10.sup.11,
10.sup.12, 10.sup.13, or 10.sup.14 CFUs/L.
[0100] In some aspects, this disclosure provides a method of
producing, e.g., manufacturing, N. eutropha, comprising contacting
N. eutropha with culture medium and culturing the N. eutropha until
about at least about 1,000 L at about 10.sup.12 CFU/L N. eutropha
are produced.
[0101] In embodiments, the method further comprises a step of
assaying the N. eutropha for one or more (e.g., 2 or 3) of an
optimized growth rate, an optimized NH.sub.4.sup.+ oxidation rate,
or an optimized resistance to NH.sub.4.sup.+.
[0102] In embodiments, the method further comprises a step of
testing the N. eutropha or culture medium for contaminating
organisms. In embodiments, the N. eutropha brought into contact
with the culture medium is an N. eutropha having one or more (e.g.,
2 or 3) of an optimized growth rate, an optimized NH.sub.4.sup.+
oxidation rate, or an optimized resistance to NH.sub.4.sup.+.
[0103] In some aspects, this disclosure provides a method of
producing, e.g., manufacturing N. eutropha, comprising:
[0104] (a) contacting N. eutropha with a culture medium; and
[0105] (b) culturing the N. eutropha for 1-2 days, thereby creating
a culture, until the culture reaches an OD600 of about 0.5-0.6.
[0106] In embodiments, the method further comprises a step of
assaying the N. eutropha for one or more of an optimized growth
rate, an optimized NH.sub.4.sup.+ oxidation rate, or an optimized
resistance to NH.sub.4.sup.+. In embodiments, the method further
comprises a step of testing the culture for contaminating
organisms, e.g., bacteria, viruses, fungi, or pathogens, or a
combination thereof. In embodiments, the N. eutropha of step (a) is
an N. eutropha having one or more (e.g., 2 or 3) of an optimized
growth rate, an optimized NH.sub.4.sup.+ oxidation rate, or an
optimized resistance to NH.sub.4.sup.+. In embodiments, the method
comprises producing at least at least about 1,000 L per day at
about 10.sup.12 CFUs/L of N. eutropha.
[0107] In some aspects, this disclosure provides a N. eutropha
bacterium produced by the methods described above.
[0108] In embodiments, a preparation of N. eutropha made by the
methods described above. In some aspects, the preparation may
comprise about 0.1 milligrams to about 100 milligrams (mg) of N.
eutropha.
[0109] In some aspects, a reaction mixture may be provided
comprising N. eutropha at an optical density of about 0.5 to about
0.6. In some aspects, this disclosure provides a method of
producing N. eutropha-bearing clothing, comprising contacting an
article of clothing with of the N. eutropha as described herein
(e.g., strain D23).
[0110] In embodiments, the method comprises producing at least 10,
100, or 1000 articles of clothing. In embodiments, the method
comprises contacting the article of clothing with at least
10.sup.10 CFUs of N. eutropha. In embodiments, the method further
comprises packaging the clothing.
[0111] In certain aspects, the present disclosure provides a method
of obtaining a formulation of N. eutropha, combining contacting N.
eutropha described herein (e.g., strain D23) with a
pharmaceutically or cosmetically acceptable excipient.
[0112] In embodiments, the method further comprises mixing the N.
eutropha and the excipient. In embodiments, the method is performed
under conditions that are substantially free of contaminating
organisms, e.g., bacteria, viruses, fungi, or pathogens.
[0113] In certain aspects, the present disclosure provides a method
of packaging N. eutropha, comprising assembling N. eutropha
described herein (e.g., strain D23) into a package.
[0114] In embodiments, the package is resistant to gaseous exchange
or resistant to water. In embodiments, the package is permeable to
gaseous exchange, NH.sub.3, NH.sub.4.sup.+, or NO.sub.2.sup.-.
[0115] In certain aspects, the present disclosure provides a method
of inhibiting microbial growth on a subject's skin, comprising
topically administering to a subject in need thereof an effective
dose of the N. eutropha bacteria described herein (e.g., strain
D23).
[0116] In embodiments, the effective dose is approximately
1.times.10.sup.9 CFU, 2.times.10.sup.9 CFU, 5.times.10.sup.9 CFU,
1.times.10.sup.10 CFU, 1.5.times.10.sup.10 CFU, 2.times.10.sup.10
CFU, 5.times.10.sup.10 CFU, or 1.times.10.sup.11 CFU. In
embodiments, the effective dose is at least about 1.times.10.sup.9
CFU, 2.times.10.sup.9 CFU, 5.times.10.sup.9 CFU, 1.times.10.sup.10
CFU, 1.5.times.10.sup.10 CFU, 2.times.10.sup.10 CFU,
5.times.10.sup.10 CFU, or 1.times.10.sup.11 CFU. In embodiments,
the effective dose is approximately 1.times.10.sup.9
CFU-2.times.10.sup.9 CFU, 2.times.10.sup.9 CFU-5.times.10.sup.9
CFU, 5.times.10.sup.9 CFU-1.times.10.sup.10 CFU, 1.times.10.sup.10
CFU-1.5.times.10.sup.10 CFU, 1.times.10.sup.10
CFU-2.times.10.sup.10 CFU 1.5.times.10.sup.10 CFU-2.times.10.sup.10
CFU, 2.times.10.sup.10 CFU-5.times.10.sup.10 CFU, or
5.times.10.sup.10 CFU-1.times.10.sup.11 CFU. In embodiments, the
bacterium is administered at a concentration of about
1.times.10.sup.8, 2.times.10.sup.8, 5.times.10.sup.8,
1.times.10.sup.9, 2.times.10.sup.9, 5.times.10.sup.9, or
1.times.10.sup.10 CFU/ml. In embodiments, the bacterium is
administered at a concentration of at least about 1.times.10.sup.8,
2.times.10.sup.8, 5.times.10.sup.8, 1.times.10.sup.9,
2.times.10.sup.9, 5.times.10.sup.9, or 1.times.10.sup.10 CFU/ml. In
embodiments, the bacterium is administered at a concentration of
about 1.times.10.sup.8-2.times.10.sup.8,
2.times.10.sup.8-5.times.10.sup.8,
5.times.10.sup.8-1.times.10.sup.9,
1.times.10.sup.9-2.times.10.sup.9,
2.times.10.sup.9-5.times.10.sup.9, or
5.times.10.sup.9-1.times.10.sup.10 CFU/ml. In embodiments, the
administration is performed twice per day. In embodiments, the
subject is a human. In embodiments, the microbial growth to be
inhibited is growth of Pseudomonas aeruginosa or Staphylococcus
aureus (S. aureus or SA), Streptococcus pyogenes (S. pyogenes or
SP), or Acinetobacter baumannii (A. baumannii or AB).
[0117] In certain aspects, the present disclosure provides a method
of supplying nitric oxide to a subject, comprising positioning an
effective dose of the N. eutropha bacteria described herein (e.g.,
strain D23) in close proximity to the subject.
[0118] In certain aspects, the present disclosure provides a method
of reducing body odor, comprising topically administering to a
subject in need thereof an effective dose of the N. eutropha
bacteria described herein (e.g., strain D23).
[0119] In certain aspects, the present disclosure provides a method
of treating a disease associated with low nitrite levels,
comprising topically administering to a subject in need thereof a
therapeutically effective dose of the N. eutropha bacteria
described herein (e.g., strain D23).
[0120] In embodiments, the disease is HIV dermatitis, infection in
a diabetic foot ulcer, atopic dermatitis, acne, e.g., acne
vulgaris, eczema, contact dermatitis, allergic reaction, psoriasis,
skin infections, vascular disease, vaginal yeast infection, a
sexually transmitted disease, heart disease, atherosclerosis,
baldness, leg ulcers secondary to diabetes or confinement to bed,
angina, particularly chronic, stable angina pectoris, ischemic
diseases, congestive heart failure, myocardial infarction, ischemia
reperfusion injury, laminitis, hypertension, hypertrophic organ
degeneration, Raynaud's phenomenon, fibrosis, fibrotic organ
degeneration, allergies, autoimmune sensitization, end stage renal
disease, obesity, impotence, or cancer.
[0121] In certain aspects, the present disclosure provides a method
of treating a skin disorder, comprising topically administering to
a subject in need thereof a therapeutically effective dose of the
N. eutropha bacteria as described herein (e.g., strain D23). In
related aspects, the disclosure provides an N. eutropha bacteria as
described herein (e.g., strain D23) for treating a disorder such as
a skin disorder. In related aspects, the disclosure provides an N.
eutropha bacteria as described herein (e.g., strain D23) for the
manufacture of a medicament, e.g., a medicament for treating a skin
disorder.
[0122] In embodiments, the skin disorder is acne, e.g., acne
vulgaris, rosacea, eczema, or psoriasis. In some embodiments, the
skin disorder is an ulcer, e.g., venous ulcer, e.g., leg ulcer,
e.g., venous leg ulcer, e.g., infection in a diabetic foot ulcer.
In some embodiments, topically administering comprises pre-treating
the subject with N. eutropha, e.g., an N. eutropha described
herein. In some embodiments, topically administering comprises
topically administering prior to occurrence of the skin disorder.
In some embodiments, topically administering comprises topically
administering subsequent to occurrence of the skin disorder.
[0123] In certain aspects, the present disclosure provides a method
of promoting wound healing or closure, comprising administering to
a wound an effective dose of the N. eutropha bacteria as described
herein (e.g., strain D23). In related aspects, the disclosure
provides an N. eutropha bacteria as described herein (e.g., strain
D23) for promoting wound healing. In related aspects, the
disclosure provides an N. eutropha bacteria as described herein
(e.g., strain D23) for the manufacture of a medicament, e.g., a
medicament for promoting wound healing.
[0124] In embodiments, the wound comprises one or more undesirable
bacteria, e.g., pathogenic bacteria. In embodiments, the wound
comprises S. aureus, P. aeruginosa, P. aeroginosa, or A.
baunannii.
[0125] In embodiments, the N. eutropha is administered to the
subject prior to occurrence of the wound. In embodiments,
administering to the wound comprises administering to the subject
prior to occurrence of the wound. In embodiments, the method
further comprises administering N. eutropha (e.g., an N. eutropha
described herein, e.g., strain D23) to the wound subsequent to
occurrence of the wound. In some aspects, the disclosure provides a
method of killing or inhibiting growth of pathogenic bacteria
comprising contacting, e.g., applying, N. eutropha bacteria (e.g.,
N. eutropha described herein, e.g., strain D23) to the skin.
[0126] In embodiments, the pathogenic bacteria contribute to one or
more of the following conditions: HIV dermatitis, an ulcer, e.g.,
venous ulcer, e.g., leg ulcer, e.g., venous leg ulcer, e.g.,
infection in a diabetic foot ulcer, atopic dermatitis, acne, e.g.,
acne vulgaris, eczema, contact dermatitis, allergic reaction,
psoriasis, uticaria, rosacea, skin infections, vascular disease,
vaginal yeast infection, a sexually transmitted disease, heart
disease, atherosclerosis, baldness, leg ulcers secondary to
diabetes or confinement to bed, angina, particularly chronic,
stable angina pectoris, ischemic diseases, congestive heart
failure, myocardial infarction, ischemia reperfusion injury,
laminitis, hypertension, hypertrophic organ degeneration, Raynaud's
phenomenon, fibrosis, fibrotic organ degeneration, allergies,
autoimmune sensitization, end stage renal disease, obesity,
impotence, pneumonia, primary immunodeficiency, epidermal lysis
bulosa, or cancer.
[0127] In embodiments, the condition is an ulcer, e.g., venous
ulcer, e.g., leg ulcer, e.g., venous leg ulcer, e.g., infection in
a diabetic foot ulcer. In embodiments, the condition is a venous
leg ulcer. In embodiments, the condition is acne, e.g., acne
vulgaris. In embodiments, the condition is acne vulgaris. In
embodiments, the pathogenic bacteria is one or more of
Propionibacterium acnes, Pseudomonas aeruginosa, Staphylococcus
aureus, Streptococcus pyogenes, or Acinetobacter baumannii. In
embodiments, the method further comprises determining whether the
subject is in need of killing or inhibiting growth of pathogenic
bacteria, e.g., determining that the subject is in need of killing
or inhibiting growth of pathogenic bacteria. In embodiments, the
method further comprises selecting the subject in need of killing
or inhibiting growth of pathogenic bacteria.
[0128] In some embodiments, the N. eutropha catalyze the following
reactions.
[0129] At a neutral pH, ammonia generated from ammonium around
neutral pH conditions is the substrate of the initial reaction. The
conversion of ammonia to nitrite takes place in two steps catalyzed
respectively by ammonia monooxygenase (Amo) and hydroxylamine
oxidoreductase (Hao), as follows:
NH.sub.3+2H.sup.++2e-+O.sub.2.fwdarw.NH.sub.2OH+H.sub.2O (A)
NH.sub.2OH+H.sub.2O.fwdarw.NO.sub.2.sup.-+4e-+5H.sup.+ (B)
[0130] In some instances, reaction B is reported as follows, to
indicate nitrous acid (HNO.sub.2) formation at low pH:
NH.sub.2OH+H.sub.2O.fwdarw.HNO.sub.2+4e-+4H.sup.+
[0131] In certain embodiments, the N. eutropha has a doubling time
of less than 4, 5, 6, 7, 8, 9, or 10 hours, for instance about 8
hours, e.g., 7-9 hours or 6-10 hours, when grown under batch
culture conditions. In some embodiments, the doubling time is at
least 3, 4, 5, or 6 hours under batch culture conditions. In some
embodiments, the N. eutropha has a doubling time of less than 16,
18, 20, 22, 24, or 26 hours, for instance about 20 hours, e.g.,
19-21 hours or 18-22 hours, when grown under chemostat (i.e.,
continuous culture) conditions. In some embodiments, the doubling
time is at least 10, 12, 14, 16, or 18 hours under chemostat
conditions.
[0132] In certain embodiments, a continuous culture of N. eutropha
at an OD600 of about 0.15-0.18 is capable of reaching an OD600 of
about 0.5-0.6 in about 1-2 days. For instance, in some embodiments,
a continuous culture of N. eutropha may grow from an OD600 of about
0.15 to at least 0.3, 0.4, 0.5, 0.6, 0.7, or 0.8 over about 1 day;
in embodiments the culture may reach an OD in range of 0.4-0.6 or
0.3-0.7 over about 1 day. In embodiments, the continuous culture of
N. eutropha may grow from an OD600 of about 0.15 to at least 0.3,
0.4, 0.5, 0.6, 0.7, or 0.8 over about 2 days; in embodiments the
culture may reach an OD in the range of 0.4-0.6 or 0.3-0.7 over
about 2 days. In some embodiments, the continuous culture
conditions comprise growth in a bioreactor in N. europaea medium,
optionally comprising about 200 mM NH.sub.4.sup.+. In some
embodiments, the continuous culture conditions are conditions set
out in Example 2.
[0133] In certain embodiments, the N. eutropha are capable of
converting NH.sub.4.sup.+ (e.g., at about 200 mM) to nitrite (e.g.,
reaching up to about 180 mM) at a rate of at least about 50, 75,
125, or 150 micromoles NO.sub.2.sup.- per minute, e.g., about
100-150, 75-175, 75-125, 100-125, 125-150, or 125-175
micromoles/minute, e.g., about 125 micromoles NO.sub.2.sup.- per
minute. In some embodiments, the reaction rates are measured in an
about 1 L chemostat culture of about 10.sup.9 CFU/ml over the
course of 24 hours.
[0134] In certain embodiments, the N. eutropha are capable of
growing in medium comprising at least 50 mM, 75 mM, 100 mM, 125 mM,
150 mM, 175 mM, 200 mM, 225 mM, 250 mM, 275 mM, or 300 mM
NH.sub.4.sup.+ (or NH.sub.3), e.g., about 150-200, 175-225,
200-250, 225-275, 250-300 mM, e.g., about 200 or about 250 mM. In
certain embodiments, the N. eutropha is grown in a bioreactor under
these concentrations of ammonium. In some embodiments, when the N.
eutropha is grown under these concentrations of ammonium, the
concentration of nitrate or nitrite is capable of reaching at least
60, 80, 100, 120, 140, 160, or 180 mM, e.g., about 140-180,
160-200, or 140-200 mM, e.g., about 160 or 180 mM.
[0135] In certain aspects, the present disclosure provides high
density cultures of N. eutropha, e.g., N. eutropha strain D23. For
instance, the high density culture composition may comprise a cell
suspension of an actively dividing culture of N. eutropha bacteria
having an OD600 of at least about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, or
0.7, e.g., about 0.2-0.6, 0.3-0.6, 0.4-0.6, 0.5-0.6, or 0.4-0.7,
wherein the composition is substantially free of other
organisms
[0136] In some embodiments, the N. eutropha are stable for at least
2 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, or 6
months when stored at 4.degree. C. In some embodiments, the method
of storage comprises resuspending the cells in a buffer comprising
one or more of Na.sub.2HPO.sub.4 and MgCl.sub.2, for instance 50 mM
Na.sub.2HPO.sub.4 and 2 mM MgCl.sub.2, for instance the storage
buffer described in Example 2. For example, the storage conditions
may be those specified in Example 2. In some embodiments, the N.
eutropha are continuously cultured at 200 mM NH.sub.4.sup.+ at a pH
of 6-8, e.g., 7, before storage at 4.degree.. Stability can include
one or more of 1) retaining viability, 2) retaining a relevant
property such as the ability to produce a given level of
nitrite.
[0137] In certain embodiments, NH.sub.4.sup.+ and NH.sub.3 may be
used interchangeably throughout the disclosure.
[0138] This disclosure provides, inter alia, a method of changing a
composition of a skin microbiome of a subject. The method comprises
administering, e.g., applying, a preparation comprising ammonia
oxidizing bacteria to a surface of the skin, wherein the amount and
frequency of administration, e.g., application, is sufficient to
reduce the proportion of pathogenic bacteria on the surface of the
skin.
[0139] Ammonia oxidizing bacteria are, in some embodiments,
ubiquitous Gram-negative obligate chemolithoautotrophic bacteria
with a unique capacity to generate energy exclusively from the
conversion of ammonia to nitrite.
[0140] In some embodiments, the method may further comprise,
selecting the subject on the basis of the subject being in need of
a reduction in the proportion of pathogenic bacteria on the surface
of the skin.
[0141] In some embodiments, the preparation comprising ammonia
oxidizing bacteria comprises at least one of ammonia, ammonium
salts, and urea.
[0142] In some embodiments, the preparation comprising ammonia
oxidizing bacteria comprises a controlled release material, e.g.,
slow release material.
[0143] In some embodiments, the preparation of ammonia oxidizing
bacteria, comprises an excipient, e.g., one of a pharmaceutically
acceptable excipient or a cosmetically acceptable excipient. The
excipient, e.g., one of the pharmaceutically acceptable excipient
and the cosmetically acceptable excipient, may be suitable for one
of topical, nasal, pulmonary, and gastrointestinal administration.
The excipient, e.g., one of the pharmaceutically acceptable
excipient and the cosmetically acceptable excipient may be a
surfactant. The surfactant may be selected from the group
consisting of cocamidopropyl betaine (ColaTeric COAB), polyethylene
sorbitol ester (e.g., Tween 80), ethoxylated lauryl alcohol
(RhodaSurf 6 NAT), sodium laureth sulfate/lauryl
glucoside/cocamidopropyl betaine (Plantapon 611 L UP), sodium
laureth sulfate (e.g., RhodaPex ESB 70 NAT), alkyl polyglucoside
(e.g., Plantaren 2000 N UP), sodium laureth sulfate (Plantaren
200), Dr. Bronner's Castile soap, lauramine oxide (ColaLux Lo),
sodium dodecyl sulfate (SDS), polysulfonate alkyl polyglucoside
(PolySufanate 160 P), sodium lauryl sulfate (Stepanol-WA Extra K),
and any combination thereof. Dr. Bronner's Castile soap comprises
water, organic coconut oil, potassium hydroxide, organic olive oil,
organic fair deal hemp oil, organic jojoba oil, citric acid, and
tocopherol. In some embodiments, the excipient comprises one or
more of, e.g., all of, water, organic coconut oil, potassium
hydroxide, organic olive oil, organic fair deal hemp oil, organic
jojoba oil, citric acid, and tocopherol.
[0144] In some embodiments, the preparation may be substantially
free of other organisms.
[0145] In some embodiments, the preparation may be disposed in a
powder, cosmetic, cream, stick, aerosol, salve, wipe, or bandage.
The preparation may be provided as a powder, cosmetic, cream,
stick, aerosol, salve, wipe, or bandage.
[0146] In some embodiments, the preparation may comprise a
moisturizing agent, deodorizing agent, scent, colorant, insect
repellant, cleansing agent, or UV-blocking agent.
[0147] In some embodiments, the excipient, e.g., the
pharmaceutically acceptable excipient or the cosmetically
acceptable excipient may comprise an anti-adherent, binder, coat,
disintegrant, filler, flavor, color, lubricant, glidant, sorbent,
preservative, or sweetener.
[0148] In some embodiments, the preparation comprising ammonia
oxidizing bacteria may comprise between about 10.sup.8 and about
10.sup.14 CFU/L. In certain aspects, the preparation may comprise
between about 1.times.10.sup.9 CFU/L and about 10.times.10.sup.9
CFU/L.
[0149] In some embodiments, the preparation comprising ammonia
oxidizing bacteria may comprise between about 50 milligrams (mg)
and about 1000 mg of ammonia oxidizing bacteria.
[0150] In some embodiments, the mass ratio of ammonia oxidizing
bacteria to the excipient, e.g., the pharmaceutically acceptable
excipient or the cosmetically acceptable excipient is in a range of
about 0.1 grams per liter to about 1 gram per liter.
[0151] In some embodiments, the preparation of ammonia oxidizing
bacteria are useful in the treatment or prevention of a disease or
condition associated with low nitrite levels, a treatment or
prevention of body odor, a treatment to supply nitric oxide to a
subject, or a treatment to inhibit microbial growth, e.g.,
pathogenic bacterial growth.
[0152] In some embodiments, the ammonia oxidizing bacteria is
selected from the group consisting of Nitrosomonas, Nitrosococcus,
Nitrosospria, Nitrosocystis, Nitrosolobus, Nitrosovibrio, and
combinations thereof. The preparation may further comprise an
organism selected from the group consisting of Lactobacillus,
Streptococcus, Bifidobacter, and combinations thereof. In certain
aspects, the preparation is substantially free of organisms other
than ammonia oxidizing bacteria.
[0153] In some embodiments, the preparation comprising ammonia
oxidizing bacteria may comprise ammonia oxidizing bacteria in a
growth state. In some embodiments, the preparation comprising
ammonia oxidizing bacteria may comprise ammonia oxidizing bacteria
in a storage state.
[0154] In some embodiments, the methods of the present disclosure
may be used to deliver a cosmetic product. In some embodiments, the
methods of the present disclosure may be used to deliver a
therapeutic product. The preparation may be useful for treatment of
at least one of HIV dermatitis, infection in a diabetic foot ulcer,
atopic dermatitis, acne, e.g., acne vulgaris, eczema, contact
dermatitis, allergic reaction, psoriasis, uticaria, rosacea, skin
infections, vascular disease, vaginal yeast infection, a sexually
transmitted disease, heart disease, atherosclerosis, baldness, leg
ulcers secondary to diabetes or confinement to bed, angina,
particularly chronic, stable angina pectoris, ischemic diseases,
congestive heart failure, myocardial infarction, ischemia
reperfusion injury, laminitis, hypertension, hypertrophic organ
degeneration, Raynaud's phenomenon, fibrosis, fibrotic organ
degeneration, allergies, autoimmune sensitization, end stage renal
disease, obesity, impotence, pneumonia, primary immunodeficiency,
epidermal lysis bulosa, or cancer.
[0155] In certain aspects, the preparation may be useful for
treatment of at least one of acne, e.g., acne vulgaris, eczema,
psoriasis, uticaria, rosacea, and skin infections.
[0156] In some embodiments, the preparation may be provided in a
container, the preparation and the container having a weight of
less than about 50, 100, 200, 300, 400, 500, 600, 700, 800, 900,
1000, 1500, or 2000 grams.
[0157] In some embodiments, the preparation has less than about
0.1% to about 10% of surfactant. In certain aspects, the
preparation may be substantially free of surfactant.
[0158] In some embodiments, the preparation may comprise a
chelator. In some embodiments, the preparation may be substantially
free of a chelator.
[0159] In some embodiments, the method may comprise applying the
preparation about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14,
15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 times per day. In certain
aspects, the preparation may be applied one time per day. In
certain other aspects, the preparation may be applied two times per
day.
[0160] In some embodiments, the preparation may be applied for
about 1-3, 3-5, 5-7, 7-9, 5-10, 10-14, 12-18, 12-21, 21-28, 28-35,
35-42, 42-49, 49-56, 46-63, 63-70, 70-77, 77-84, or 84-91 days. In
certain aspects, the preparation may be applied for about 16
days.
[0161] In some embodiments, the method may further comprise
obtaining a sample from the surface of the skin. In certain
aspects, the method may further comprise isolating DNA of bacteria
in the sample. In certain aspects, the method may further comprise
sequencing DNA of bacteria in the sample.
[0162] In some embodiments, administering the ammonia oxidizing
bacteria provides for an increase in the proportion of
non-pathogenic bacteria on the surface. In certain aspects, the
non-pathogenic bacteria may be commensal non-pathogenic bacteria.
In certain aspects, the non-pathogenic bacteria is commensal
non-pathogenic bacteria of a genus of Staphylococcus. In certain
aspects, the non-pathogenic bacteria may be commensal
non-pathogenic bacteria Staphylococcus epidermidis.
[0163] In some embodiments, the proportion of non-pathogenic
bacteria Staphylococcus is, or is identified as being, increased
after about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 weeks. In certain
aspects, the proportion of non-pathogenic bacteria Staphylococcus
epidermidis Staphylococcus is, or is identified as being, increased
after about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 weeks.
[0164] In some embodiments, potentially pathogenic or disease
associated Propionibacteria is, or is identified as being, reduced
after about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 weeks.
[0165] In some embodiments, potentially pathogenic or disease
associated Stenotrophomonas is, or is identified as being, reduced
after about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 weeks.
[0166] In some embodiments, the surface of the skin comprises a
wound.
[0167] In some embodiments, a method of treating acne e.g., acne
vulgaris, may be provided by one or more methods of the present
disclosure. In some embodiments, a method of treating eczema may be
provided by one or more methods of the present disclosure. In some
embodiments, a method of treating psoriasis may be provided by one
or more methods of the present disclosure. In some embodiments, a
method of treating uticaria may be provided by one or more methods
of the present disclosure. In some embodiments, a method of
treating rosacea may be provided by one or more methods of the
present disclosure. In some embodiments, a method of treating skin
infection may be provided by one or more methods of the present
disclosure. In some embodiments, a method of reducing an amount of
undesirable bacteria on a surface of a subject is provided.
[0168] In some embodiments, the method herein (e.g., a method of
administering a N. eutropha bacterium, e.g., a bacterium of strain
D23 to a subject in need thereof), further comprise treating the
subject with an antibiotic. In embodiments, the antibiotic is
Tetracycline, a Lincosamide such as Clindamycin, a Macrolide such
as Erythromycin, an Aminoglycoside such as Gentamicin, a
.beta.-lactam such as Piperacillin, .beta.-lactamase inhibitor such
as Tazobactam, or any combination thereof (such as a combination of
a .beta.-lactam such as Piperacillin and a .beta.-lactamase
inhibitor such as Tazobactam). In some embodiments, the antibiotic
is an antibiotic to which the bacterium is sensitive. In
embodiments, the antibiotic is administered after the bacterium has
achieved the desired therapeutic effect. In embodiments, the
antibiotic is an antibiotic to which the bacterium is resistant. In
embodiments, the antibiotic is administered before or during the
period in which the bacterium is producing its therapeutic
effect.
[0169] It is understood that compositions and methods herein
involving a bacterium can also involve a plurality of bacteria. For
instance, a method of administering a N. eutropha bacterium can
also involve administering a plurality of N. eutropha bacteria.
[0170] The present disclosure also provides, in certain aspects, a
nucleic acid comprising a sequence of consecutive nucleotides
(e.g., 15-100 nucleotides) from within the D23 genome, e.g., a
sequence of a gene provided herein, e.g., a gene described in Table
1, FIG. 6-8 or Supplementary Table 1, or SEQ ID NO: 66, or a
reverse complement of any of the foregoing. In a related aspect,
the present disclosure provides a nucleic acid comprising a
sequence of consecutive nucleotides (e.g., 15-100 nucleotides) from
within SEQ ID NO: 1 or a reverse complement thereof. In a related
aspect, the present disclosure provides a nucleic acid comprising a
sequence of consecutive nucleotides (e.g., 15-100 nucleotides) from
within a gene of Table 1 (e.g., a sequence of SEQ ID NO: 5, 7, 9,
11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, or 33) or a reverse
complement thereof.
[0171] In some embodiments, the nucleic acid has a non-naturally
occurring sequence or another modification such as a label, or
both. In some embodiments, the sequence of consecutive nucleotides
is not a sequence found in N. Eutropha strain C91. In some
embodiments, the nucleic acid comprises a heterologous sequence 5'
to the sequence of 15-100 consecutive nucleotides, or a
heterologous sequence 3' to the sequence of 15-100 consecutive
nucleotides, or both. In some embodiments, the nucleic acid has a
length of 10-15, 15-20, 20-25, 25-30, 30-24, 35-40 nucleotides. In
some embodiments, the nucleic acid is bound, e.g., covalently
bound, to a detectable label, e.g., a fluorescent label. In some
embodiments, the nucleic acid comprises 10-15, 15-20, 20-25, 25-30,
30-24, 35-40, 40-50, 50-60, 60-70, 70-80, 80-90, or 90-100
consecutive nucleotides from within the D23 genome. In some
embodiments, the nucleic acid comprises at least about 10, 15, 20,
25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350,
400, 450, 500, 600, 700, 800, 900, or 1000 consecutive nucleotides
from within the D23 genome. In some embodiments, the nucleic acid
is DNA.
[0172] In some aspects, the disclosure provides a composition or a
kit comprising a first nucleic acid and a second nucleic acid. In
some embodiments, the first nucleic acid comprises consecutive
nucleotides (e.g., 15-100) from within SEQ ID NO: 1, SEQ ID NO: 66,
a gene of FIGS. 6-8, or a gene of Table 1, or a reverse complement
thereof. In some embodiments, the second nucleic acid comprises
consecutive nucleotides (e.g., 15-100) from within SEQ ID NO: 1,
SEQ ID NO: 66, a gene of FIGS. 6-8, or a gene of Table 1, or a
reverse complement thereof. In some embodiments, the nucleic acid
has a non-naturally occurring sequence, e.g., a sequence not found
in N. eutropha strain C91. In some embodiments, the first nucleic
acid and the second nucleic acid define an amplicon in a gene of
Table 1, e.g., a sequence of SEQ ID NO: 5, 7, 9, 11, 13, 15, 17,
19, 21, 23, 25, 27, 29, 31, or 33) or a reverse complement
thereof.
[0173] In some embodiments, the first nucleic acid has a sequence
that corresponds to a first region of SEQ ID NO: 1, and the reverse
complement of the second nucleic acid has a sequence that
corresponds to a second region of SEQ ID NO: 1, and the first and
second regions are separated by a distance suitable for PCR. In
some embodiments, the reverse complement of the first nucleic acid
has a sequence that corresponds to a first region of SEQ ID NO: 1,
and the second nucleic acid has a sequence that corresponds to a
second region of SEQ ID NO: 1, and the first and second regions are
separated by a distance suitable for PCR. In an embodiment, the
distance suitable for PCR is no more than 50, 100, 150, 200, 250,
300, 350, 400, 450, 500, 600, 700, 800, 900, or 1000 nucleotides of
SEQ ID NO: 1. In some embodiments, the first nucleic acid and
second nucleic acid delineate an amplicon in SEQ ID NO: 1. In some
embodiments, the first nucleic acid and second nucleic acid each
has a melting temperature (Tm) suitable for PCR, e.g., about
55-65.degree. or about 60-65.degree. C. In some embodiments, the Tm
of the first nucleic acid is within 10, 9, 8, 7, 6, 5, 4, 3, 2, or
1.degree. C. of the Tm of the second nucleic acid.
[0174] In some embodiments, the first nucleic acid, the second
nucleic acid, or each of the first nucleic acid and second nucleic
acid further comprises a heterologous sequence 5' to the sequence
of consecutive nucleotides. Alternatively or in combination, in
some embodiments, the first nucleic acid, the second nucleic acid,
or each of the first nucleic acid and second nucleic acid further
comprises a heterologous sequence 3' to the sequence of consecutive
nucleotides from within SEQ ID NO: 1 or SEQ ID NO: 66. In some
embodiments, the first nucleic acid, the second nucleic acid, or
each of the first nucleic acid and second nucleic acid has a length
of 15-20, 20-25, 25-30, 30-24, or 35-40 nucleotides. In some
embodiments, the first nucleic acid, the second nucleic acid, or
each of the first nucleic acid and second nucleic acid is bound,
e.g., covalently bound, to a detectable label, e.g., a fluorescent
label. In some embodiments, the first nucleic acid comprises, or
consists of, a sequence of SEQ ID NO: 64. In some embodiments, the
second nucleic acid comprises, or consists of, a sequence of SEQ ID
NO: 65. In some embodiments, the first nucleic acid, the second
nucleic acid, or both, are DNA.
[0175] In some embodiments, the composition or kit comprises at
least two (e.g., 3, 4, 5, 6, 7, 8, 9, or 10) pairs of primers, each
pair recognizing an amplicon in a gene of Table 1 (e.g., a sequence
of SEQ ID NO: 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31,
or 33) or a reverse complement thereof. In some embodiments, a
first pair of primers recognizes an amplicon in an Amo gene (e.g.,
AmoA1, AmoA2, AmoB1, AmoB2, AmoC1, AmoC2, or AmoC3) and the second
pair of primers recognizes an amplicon in an Amo gene (e.g., AmoA1,
AmoA2, AmoB1, AmoB2, AmoC1, AmoC2, or AmoC3). In some embodiments,
a first pair of primers recognizes an amplicon in an AmoA gene
(e.g., AmoA1 or AmoA2). In some embodiments, a second pair of
primers recognizes an amplicon in an AmoB gene (e.g., AmoB1 or
AmoB2). In some embodiments, a third pair of primers recognizes an
amplicon in an AmoC gene (e.g., AmoC1, AmoC2, or AmoC3).
[0176] In some embodiments, the kit comprises a first container in
which the first nucleic acid is disposed and a second container in
which the second nucleic acid is disposed. The kit may comprise
additional containers, e.g., for a third, fourth, fifth, or sixth
nucleic acid. In some embodiments, a pair of primers recognizing an
amplicon is stored in a single container.
[0177] The present disclosure also provides, in some aspects, a
nucleic acid comprising, or consisting of, the sequence of SEQ ID
NO: 64. The present disclosure also provides, in some aspects, a
nucleic acid comprising, or consisting of, the sequence of SEQ ID
NO: 65. The present disclosure also provides, in some aspects, the
present disclosure provides a molecule comprising a nucleic acid
described herein and a detectable label, e.g., a fluorescent label.
The nucleic acid may consist of a sequence of SEQ ID NO: 64 or SEQ
ID NO: 65, for example.
[0178] The present disclosure provides, in some aspects, a
composition comprising a first molecule and a second molecule. In
some embodiments, the first molecule comprises a nucleic acid
described herein, e.g., a nucleic acid consisting of the sequence
of SEQ ID NO: 64, and optionally comprises a detectable label,
e.g., a fluorescent label. In some embodiments, the second molecule
comprises a nucleic acid described herein, e.g., a nucleic acid
consisting of the sequence of SEQ ID NO: 65, and optionally
comprises a detectable label, e.g., a fluorescent label.
[0179] In some embodiments, the kit comprises a first container in
which the first molecule is disposed and a second container in
which the second molecule is disposed.
[0180] In some embodiments, a kit described herein further
comprises one or more of a buffer, an enzyme (e.g., a polymerase
such as a thermostable polymerase such as Taq), nucleotides (e.g.,
dNTPs), and chain-terminating nucleotides (e.g., dideoxy
nucleotides) which are optionally dye-labeled; these components may
be provided separately or as part of a single composition.
[0181] In certain aspects, this disclosure provides a method of
detecting whether a D23 N. eutropha nucleic acid is present in a
sample, comprising: performing a polymerase chain reaction (PCR) on
the sample using primers specific to D23 N. eutropha, and
determining whether a PCR product is produced, wherein the presence
of a PCR product indicates that the D23 N. eutropha nucleic acid
was present in the sample. In embodiments, at least two PCR
reactions are performed, e.g., 3, 4, 5, 6, 7, 8, 9 or 10 PCR
reactions. In embodiments, the PCR reactions are performed in
separate reaction volumes. In embodiments, two or more PCR
reactions are performed in multiplex.
[0182] In some embodiments, the primers specific to D23 N. eutropha
are a first nucleic acid and second nucleic acid described herein,
e.g., a first and second nucleic acid from a composition or kit
described herein. In some embodiments, the first primer comprises
or consists of a sequence of SEQ ID NO: 65, and the second primer
comprises or consists of a sequence of SEQ ID NO: 66.
[0183] In some embodiments, the PCR reaction is a quantitative or
real-time PCR reaction. In some embodiments, the PCR reaction
comprises a TaqMan reaction. In some embodiments, the PCR reaction
comprises cycling the temperature of a reaction mixture between a
denaturing temperature (e.g., about 95.degree. C.), an annealing
temperature (e.g., 45-68, 55-65, or 60-65.degree. C.), and an
elongation temperature (e.g., about 68.degree. C.) for a number of
cycles sufficient to produce a detectable PCR product, e.g., about
10, 15, 20, 25, or 30 cycles. In some embodiments, detecting the
PCR product comprises detecting fluorescence from the PCR product.
In some embodiments, a positive control is performed, e.g., using a
known D23 N. eutropha nucleic acid as a template. In some
embodiments, a negative control is used, e.g., using no template or
using another bacterial nucleic acid as a template.
[0184] In certain aspects, the disclosure provides a method of
detecting whether a D23 N. eutropha nucleic acid is present in a
sample, comprising detecting binding of a nucleic acid described
herein to a sample, wherein the presence of binding indicates that
the D23 N. eutropha nucleic acid was present in the sample. In some
embodiments, binding is detected by primer extension or RNase
protection.
[0185] In some embodiments of the methods herein, the sample
comprises at least 2, 3, 4, 5, 6, 7, 8, 9, or 10 strains of
bacteria. In some embodiments, the sample is from the skin of a
subject, e.g., a human subject. In some embodiments, the methods
herein comprise detecting one or more additional types of bacterium
in the sample, e.g., Pseudomonas aeruginosa, Staphylococcus aureus,
Streptococcus pyogenes, or Acinetobacter baumannii.
[0186] The disclosure contemplates all combinations of any one or
more of the foregoing aspects and/or embodiments, as well as
combinations with any one or more of the embodiments set forth in
the detailed description and examples.
BRIEF DESCRIPTION OF THE DRAWINGS
[0187] FIG. 1 shows the growth of a mixed culture of bacteria
comprising N. eutropha strain D23. The optical density at a 600 nm
wavelength is plotted relative to time.
[0188] FIG. 2A shows the nitrite production of a mixed culture of
bacteria comprising N. eutropha strain D23. The nitrite
concentration is plotted relative to time.
[0189] FIG. 2B-I shows the nitrite production kinetics by N.
eutropha D23 in batch culture. The nitrite concentration is plotted
relative to time.
[0190] FIG. 2B-II shows the nitrite production kinetics by N.
eutropha D23 in vitro. The nitrite concentration is plotted
relative to time.
[0191] FIG. 2C shows N. eutropha D23 stability upon storage at
4.degree. C. The nitrite concentration is plotted relative to
time.
[0192] FIG. 3A shows the N. eutropha D23's ability to inhibit the
growth of P. aeruginosa (left panel) and S. aureus (right panel) in
co-culture experiments. The amount of each type of undesirable
bacteria (in CFU/ml) is plotted relative to time. In this figure,
"AOB" refers to strain D23.
[0193] FIG. 3B shows the N. eutropha D23's ability to inhibit the
growth of Streptococcus pyogenes (left panel) and Acinetobacter
baumannii (right panel) in co-culture experiments. The amount of
each type of undesirable bacteria (in CFU/ml) is plotted relative
to time. In this figure, "AOB" refers to strain D23.
[0194] FIG. 3C shows the N. eutropha D23's ability to inhibit the
growth of Propionibacterium acnes in co-culture experiments. The
amount of each type of undesirable bacteria (in CFU/ml) is plotted
relative to time. In this figure, "AOB" refers to strain D23.
[0195] FIG. 4A (top panel) plots the NO.sub.2.sup.- concentration
over time in a co-culture experiment. The bottom panel plots pH
over time in a co-culture experiment.
[0196] FIG. 4B (top panels) plots the CFU/ml of the indicated
bacteria over time in a co-culture experiment. The center panels
plot the NO.sub.2.sup.- concentration over time in a co-culture
experiment.
[0197] The bottom panels plot pH over time in a co-culture
experiment.
[0198] FIG. 4C plots the microbicidal activity of D23 against skin
pathogens.
[0199] FIG. 4D plots the microbicidal activity of D23 against skin
pathogens.
[0200] FIG. 4E shows an alternative plot of microbicidal activity
of D23 against skin pathogens.
[0201] FIG. 5A plots the percent wound closure over time in an
experiment testing D23's ability to improve wound healing.
[0202] FIG. 5B plots CT.sub.50 for various D23 treatments.
[0203] FIG. 5C plots the percent wound closure over time in an
experiment testing D23's ability to improve wound healing.
[0204] FIG. 5D plots the percent wound closure over time in an
experiment testing D23's ability to improve wound healing.
[0205] FIG. 5E plots CT.sub.50 for various D23 treatments.
[0206] FIG. 5F shows images of D23 enhanced wound healing in
diabetic mice at Day 1, Day 11, and Day 15.
[0207] FIG. 5G shows blood glucose measurements for various
concentrations of D23.
[0208] FIG. 5H shows body weight of test subjects over the course
of testing.
[0209] FIG. 5I shows body weight of test subjects over the course
of testing.
[0210] FIG. 5J shows PCR scores for a scalp test of subjects. AOB
refers to D23 in this Figure.
[0211] FIG. 5K shows a schematic of a human volunteer study for an
evaluation of a Nitrosomonas-containing topical suspension
(AOB-001).
[0212] FIG. 5L (left panel) shows PCR analyses of scalp swabs
collected during the study. Percent-positive samples for
AOB-specific three-gene signature (amoA, amoB, amoC). The right
panel shows PCR analyses of scalp swabs collected during the study.
Composite PCR scores for a total of six samples collected from each
of 23 volunteers. The scoring scheme used for the positive samples
collected at each of six sampling points is indicated.
[0213] FIG. 5M shows genus-level bacterial diversity as determined
by 16S rDNA sequencing in skin swab samples collected before and
after topical application of AOB-001. The percentage of the total
sequence reads representing each of twelve bacterial genera in
samples collected at baseline prior to application (Day 0) and
immediately after the one week application (Day 8), or one week
after stopping topical application (Day 14), are shown. The
proportions of Acinetobacter, Burkholderia, Enterobacter,
Escherichia Shigella, Klebsiella, Nitrosomonas, Pantoea,
Propionibacterium, Pseudomonas, Serratia, Staphylococcus, and
Stenotrophomonas are shown.
[0214] FIG. 5N-A shows changes in abundance of Nitrosomonas and
other species in skin samples collected before and after AOB-001
application. The percentages of the total 16S rDNA sequence reads
representing Nitrosomonas prior to application (Day 0), immediately
after the one-week application (Day 8), or one week after
terminating application (Day 14) are shown.
[0215] FIG. 5N-B shows changes in abundance of Nitrosomonas and
other species in skin samples collected before and after AOB-001
application. Changed patterns in abundance of species were detected
by 16S rDNA sequencing in Day 0 versus Day 8 samples collected from
AOB users.
[0216] FIG. 5O shows user evaluation of AOB-001. Assessment of
AOB-001 cosmetic effects as provided by 23 volunteers upon
completion of the one week application to their scalp and face.
Subjects were plotted in order of increasing composite PCT scores.
(2=agree strongly; 0=no change; -2=disagree strongly).
[0217] FIG. 6 is a table displaying unique D23 genes that have
either an assigned open reading frame (ORF) number and a function
based on sequence analysis, or a hypothetical gene above 200 base
pairs in length. The column headers signify as follows:
Feature.ID=a unique identifier for the gene; Type=type of gene,
where CDS indicates a protein-coding DNA sequence; Start=starting
position of gene in the genome sequence of SEQ ID NO: 1; Stop=end
of gene in the genome sequence of SEQ ID NO: 1; Frame=reading
frame; Length=length of gene in base pairs; Function=gene or
protein function based on sequence analysis; Subsystem=category of
gene function; D23GbkId=a gene identifier.
[0218] FIG. 7 is a table displaying unique D23 genes below 200 base
pairs that have an assigned ORF number. Column headers are as
described in FIG. 6.
[0219] FIG. 8 is a table displaying unique D23 genes with no
assigned ORF number. Column headers are as described in FIG. 6.
[0220] FIG. 9 lists unique C91 genes that do not have a homolog in
D23.
[0221] FIG. 10 is a sequence alignment between the AmoA1 and AmoA2
proteins in N. eutropha strains D23 and C91. The SEQ ID of each
protein is listed in Table 1. FIG. 10 discloses SEQ ID NOS 6, 12,
36 and 42, respectively, in order of appearance.
[0222] FIG. 11 is a sequence alignment between the AmoB1 and AmoB2
proteins in N. eutropha strains D23 and C91. The SEQ ID of each
protein is listed in Table 1. FIG. 11 discloses SEQ ID NOS 8, 14,
38 and 44, respectively, in order of appearance.
[0223] FIG. 12 is a sequence alignment between the AmoC1 and AmoC2
proteins in N. eutropha strains D23 and C91. The SEQ ID of each
protein is listed in Table 1. FIG. 12 discloses SEQ ID NOS 34, 40,
10 and 4, respectively, in order of appearance.
[0224] FIG. 13 is a sequence alignment between the AmoC3 proteins
in N. eutropha strains D23 and C91. The SEQ ID of each protein is
listed in Table 1. FIG. 13 discloses SEQ ID NOS 46 and 16,
respectively, in order of appearance.
[0225] FIG. 14 A and FIG. 14 B show a sequence alignment between
the Hao1, Hao2, and Hao3 proteins in N. eutropha strains D23 and
C91. The SEQ ID of each protein is listed in Table 1. FIG. 14
discloses SEQ ID NOS 20, 22, 18, 50, 52 and 48, respectively, in
order of appearance.
[0226] FIG. 15 is a sequence alignment between the cycA1, cycA2,
and cycA3 genes in N. eutropha strains D23 and C91. The SEQ ID of
each protein is listed in Table 1. FIG. 15 discloses SEQ ID NOS 26,
28, 24, 58, 56 and 54, respectively, in order of appearance.
[0227] FIG. 16 is a sequence alignment between the cycB1 and cycB2
genes in N. eutropha strains D23 and C91. The SEQ ID of each
protein is listed in Table 1. FIG. 16 discloses SEQ ID NOS 30, 32,
60 and 62, respectively, in order of appearance.
[0228] FIG. 17 shows a bar graph of proportion of bacteria, by
genus versus day.
[0229] FIG. 18 shows a bar graph of proportion of bacteria, by
genus versus bacteria genus, for day 0, day 1, day 8, day 14, and
day 16.
[0230] Supplementary Table 1 displays the genome annotation of
2,777 genes identified in strain D23 using sequence analysis.
Column headers are as described in FIG. 6. "C91 Alias" refers to a
homolog in strain C91. Supplementary Table 1 is appended to the end
of the Detailed Description and Examples.
[0231] Supplementary Table 2 displays the sequences of selected
proteins genes identified in strain D23. Supplementary Table 2 is
appended to the end of the Detailed Description and Examples.
DETAILED DESCRIPTION
[0232] Ammonia-oxidizing bacteria (AOB) of the genus Nitrosomonas
are Gram-negative obligate autotrophic bacteria with a unique
capacity to generate nitrite and nitric oxide exclusively from
ammonia as an energy source. They are widely present both in soil
and water environments and are essential components of
environmental nitrification processes. Due to the roles of nitrite
and nitric oxide on human skin as important components of several
physiological functions, such as vasodilation, skin inflammation
and wound healing, these bacteria may have beneficial properties
for both healthy and immunopathological skin conditions. These
bacteria may be safe for use in humans because they are
slow-growing, cannot grow on organic carbon sources, may be
sensitive to soaps and antibiotics, and have never been associated
with any disease or infection in animals or humans.
1. DEFINITIONS
[0233] An ammonia oxidizing bacterium refers to a bacterium capable
of oxidizing ammonia or ammonium to nitrite at a rate, e.g., a
substantial rate, e.g., a pre-determined rate, e.g., at least the
rate depicted in any one of FIG. 2A, 2B, 2C, 4A, 4B, or 5 or at
least 90%, 80%, 70%, 60%, 50%, 40%, 30%, 20%, or 10% of that rate.
In some embodiments, the substantial rate refers to the conversion
of ammonium ions (NH.sub.4.sup.+)(e.g., at about 200 mM) to nitrite
(NO.sub.2.sup.-) at a rate of at least 50, 75, 125, or 150
micromoles NO.sub.2.sup.- per minute, e.g., about 100-150, 75-175,
75-125, 100-125, 125-150, or 125-175 micromoles/minute, e.g., about
125 micromoles NO.sub.2.sup.- per minute. Examples of ammonia
oxidizing bacteria include N. eutropha strains D23 and C91, and
other bacteria in the genera Nitrosomonas, Nitrosococcus,
Nitrosospira, Nitrosocystis, Nitrosolobus, and Nitrosovibrio. D23
Nitrosomonas eutropha strain refers to the strain, designated AOB
D23-100, deposited with the American Tissue Culture Collection
(ATCC) on Apr. 8, 2014 having accession number PTA-121157. The D23
Nitrosomonas eutropha of accession number PTA-121157 has a genome
sequence as set out in SEQ ID NO: 1 herein. The nucleic acid
sequence(s), e.g., genome sequence, of accession number PTA-121157
are hereby incorporated by reference in their entireties.
[0234] Optimized Nitrosomonas eutropha (N. eutropha), as that term
is used herein, refers to an N. eutropha having an optimized growth
rate; an optimized NH.sub.4.sup.+ oxidation rate; or optimized
resistance to NH.sub.4.sup.+. In an embodiment it differs from
naturally occurring N. eutropha by at least one nucleotide, e.g., a
nucleotide in a gene selected from ammonia monooxygenase,
hydroxylamine oxidoreductase, cytochrome c554, and cytochrome
c.sub.M552. The difference can arise, e.g., through selection of
spontaneously arising mutation, induced mutation, or directed
genetic engineering, of the N. eutropha. In an embodiment it
differs from a naturally occurring N. eutropha in that it has a
constellation of alleles, not present together in nature. These
differences may provide for one or more of a treatment or
prevention of a skin disorder, a treatment or prevention of a
disease or condition associated with low nitrite levels, a
treatment or prevention of body odor, a treatment to supply nitric
oxide to a subject, and a treatment to inhibit microbial
growth.
[0235] As used herein, "axenic" refers to a composition comprising
an organism that is substantially free of other organisms. For
example, an axenic culture of ammonia oxidizing bacteria is a
culture that is substantially free of organisms other than ammonia
oxidizing bacteria. For example, an axenic culture of N. eutropha
is a culture that is substantially free of organisms other than N.
eutropha. In some embodiments, "substantially free" denotes
undetectable by a method used to detect other organisms, e.g.,
plating the culture and examining colony morphology, or PCR for a
conserved gene such as 16S RNA. An axenic composition may comprise
elements that are not organisms, e.g., it may comprise nutrients or
excipients. Any embodiment, preparation, composition, or
formulation of ammonia oxidizing bacteria discussed herein may
comprise, consist essentially of, or consist of optionally axenic
ammonia oxidizing bacteria.
[0236] Throughout this disclosure, formulation may refer to a
composition or preparation.
[0237] As used herein, an "autotroph", e.g., an autotrophic
bacterium, is any organism capable of self-nourishment by using
inorganic materials as a source of nutrients and using
photosynthesis or chemosynthesis as a source of energy. Autotrophic
bacteria may synthesize organic compounds from carbon dioxide and
ATP derived from other sources, oxidation of ammonia to nitrite,
oxidation of hydrogen sulfide, and oxidation of Fe.sup.2+ to
Fe.sup.3+ Autotrophic bacteria of the present disclosure are
incapable of causing infection.
[0238] Administered "in combination," as used herein, means that
two (or more) different treatments are delivered to the subject
during the course of the subject's affliction with the disorder,
e.g., the two or more treatments are delivered after the subject
has been diagnosed with the disorder and before the disorder has
been cured or eliminated. In some embodiments, the delivery of one
treatment is still occurring when the delivery of the second
begins, so that there is overlap. This is sometimes referred to
herein as "simultaneous" or "concomitant" or "concurrent delivery".
In other embodiments, the delivery of one treatment ends before the
delivery of the other treatment begins. This is sometimes referred
to herein as "successive" or "sequential delivery." In embodiments
of either case, the treatment is more effective because of combined
administration. For example, the second treatment is a more
effective, e.g., an equivalent effect is seen with less of the
second treatment, or the second treatment reduces symptoms to a
greater extent, than would be seen if the second treatment were
administered in the absence of the first treatment, or the
analogous situation is seen with the first treatment. In some
embodiments, delivery is such that the reduction in a symptom, or
other parameter related to the disorder is greater than what would
be observed with one treatment delivered in the absence of the
other. The effect of the two treatments can be partially additive,
wholly additive, or greater than additive (i.e., synergistic). The
delivery can be such that an effect of the first treatment
delivered is still detectable when the second is delivered.
[0239] Complete N. europaea medium refers to the N. europaea growth
medium described in Ensign et al., "In vitro activation of ammonia
monooxygenase from Nitrosomonas europaea by copper." J Bacteriol.
1993 April; 175(7):1971-80.
[0240] To "culture" refers to a process of placing an amount of a
desired bacterium under conditions that promote its growth, i.e.,
promoting cell division. The conditions can involve a specified
culture medium, a set temperature range, and/or an agitation rate.
Bacteria can be cultured in a liquid culture or on plates, e.g.,
agar plates.
[0241] The term "isolated," as used herein, refers to material that
is removed from its original or native environment (e.g., the
natural environment if it is naturally occurring). For example, a
naturally-occurring polynucleotide or polypeptide present in a
living animal is not isolated, but the same polynucleotide or
polypeptide, separated by human intervention from some or all of
the co-existing materials in the natural system, is isolated. Such
polynucleotides could be part of a vector and/or such
polynucleotides or polypeptides could be part of a composition, and
still be isolated in that such vector or composition is not part of
the environment in which it is found in nature.
[0242] The terms "nucleic acid," "nucleic acid sequence,"
"nucleotide sequence," or "polynucleotide sequence," and
"polynucleotide" are used interchangeably. They refer to a
polymeric form of nucleotides of any length, e.g.,
deoxyribonucleotides or ribonucleotides, or analogs thereof. The
polynucleotide may be either single-stranded or double-stranded,
and if single-stranded may be the coding strand or non-coding
(antisense) strand. A polynucleotide may comprise modified
nucleotides, such as methylated nucleotides and nucleotide analogs.
The sequence of nucleotides may be interrupted by non-nucleotide
components. A polynucleotide may be further modified after
polymerization, such as by conjugation with a labeling
component.
[0243] The nucleic acid may be a recombinant polynucleotide, or a
polynucleotide of genomic, cDNA, semisynthetic, or synthetic origin
which either does not occur in nature or is linked to another
polynucleotide in a nonnatural arrangement.
[0244] As used herein, the term "optimized growth rate" refers to
one or more of: a doubling time of less than about 4, 5, 6, 7, 8,
9, or 10 hours when cultured under batch conditions as described
herein in Example 2; a doubling time of less than about 16, 18, 20,
22, 24, or 26 hours, when grown under chemostat conditions as
described herein in Example 2; or growing from an OD600 of about
0.15 to at least about 0.3, 0.4, 0.5, 0.6, 0.7, or 0.8 over about 1
or 2 days. In an embodiment, optimized growth rate is one having a
doubling time that it is at least 10, 20, 30, 40, or 50% shorter
than that of a naturally occurring N. eutropha.
[0245] As used herein, "optimized NH.sub.4.sup.+ oxidation rate"
refers to a rate of at least about 50, 75, 125, or 150 micromoles
per minute of converting NH.sub.3 or NH.sub.4.sup.+ into
NO.sub.2.sup.-. For instance, the rate may be at least about 50,
75, 125, or 150 micromoles per minute of converting NH.sub.4.sup.+
(e.g., at about 200 mM) to NO.sub.2.sup.-. In an embodiment, an
optimized NH.sub.4.sup.+ oxidation rate is one in which NH.sub.3 or
NH.sub.4.sup.+ is converted into NO.sub.2.sup.-' at least 10, 20,
30, 40, or 50% more rapidly than is seen with a naturally occurring
N. eutropha.
[0246] Percent (%) amino acid sequence identity, with respect to
the amino acid sequences here (e.g., proteins expressed by N.
eutropha D23) is defined as the percentage of amino acid residues
in a candidate sequence that are identical with the amino acid
residues in the reference sequence, which may be a
naturally-occurring N. eutropha sequence or an N. eutropha D23
sequence, after aligning the sequences and introducing gaps, if
necessary, to achieve the maximum percent sequence identity, and
not considering any conservative substitutions as part of the
sequence identity. Alignment for purposes of determining percent
amino acid sequence identity can be achieved in various ways that
are within the means of those skilled in the art, for instance,
using publicly available computer software such as BLAST, ALIGN or
Megalign (DNASTAR) software. Those skilled in the art can determine
appropriate parameters for measuring alignment, including any
algorithms needed to achieve maximal alignment over the full length
of the sequences being compared. For instance, the WU-BLAST-2
software may be used to determine amino acid sequence identity
(Altschul et al, Methods in Enzymology 266, 460-480 (1996);
http://blast.wustl/edu/blast/README.html). WU-BLAST-2 uses several
search parameters, most of which are set to the default values. The
adjustable parameters are set with the following values: overlap
span=1, overlap fraction=0.125, world threshold (T)=I 1. HSP score
(S) and HSP S2 parameters are dynamic values and are established by
the program itself, depending upon the composition of the
particular sequence, however, the minimum values may be adjusted as
appropriate.
[0247] Amino acid substitutions can be the result of replacing one
amino acid with another amino acid having similar structural and/or
chemical properties, such as the replacement of a leucine with a
serine, i.e., conservative amino acid replacements. Typical but not
limiting conservative substitutions are the replacements, for one
another, among the aliphatic amino acids Ala, Val, Leu and Ile;
interchange of Ser and Thr containing hydroxy residues, interchange
of the acidic residues Asp and Glu, interchange between the
amide-containing residues Asn and Gln, interchange of the basic
residues Lys and Arg, interchange of the aromatic residues Phe and
Tyr, and interchange of the small-sized amino acids Ala, Ser, Thr,
Met and Gly. Additional conservative substitutions include the
replacement of an amino acid by another of similar spatial or
steric configuration, for example the interchange of Asn for Asp,
or Gln for Glu. Amino acid substitutions can also be the result of
replacing one amino acid with another amino acid having dis-similar
structural and/or chemical properties, i.e., non-conservative amino
acid replacements. Insertions or deletions may optionally be in the
range of 1 to 5 amino acids. The variation allowed may be
determined by systematically making insertions, deletions or
substitutions of amino acids in the sequence and testing the
resulting variants for activity in the in vivo or in vitro assays
for, e.g., metabolizing urea or ammonia.
[0248] Percent (%) sequence identity with respect to the nucleic
acid sequences here (e.g., the N. eutropha D23 genome and portions
thereof) is defined as the percentage of nucleotides in a candidate
sequence that are identical with the nucleotides in the reference
sequence, which may be a naturally-occurring N. eutropha sequence
or an N. eutropha D23 sequence, after aligning the sequences and
introducing gaps, if necessary, to achieve the maximum percent
sequence identity. Alignment for purposes of determining percent
nucleotide sequence identity can be achieved in various ways that
are within the means of those skilled in the art, for instance,
using publicly available computer software such as BLAST. Those
skilled in the art can determine appropriate parameters for
measuring alignment, including any algorithms needed to achieve
maximal alignment over the full length of the sequences being
compared.
[0249] The terms "polypeptide", "peptide" and "protein" (if single
chain) are used interchangeably herein to refer to amino acid
polymers. The polymer may be linear or branched, it may comprise
modified amino acids, and it may be interrupted by non-amino acids.
The terms also encompass an amino acid polymer that has been
modified; for example, disulfide bond formation, glycosylation,
lipidation, acetylation, phosphorylation, or any other
manipulation, such as conjugation with a labeling component. The
polypeptide can be isolated from natural sources, can be a produced
by recombinant techniques from a eukaryotic or prokaryotic host, or
can be a product of synthetic procedures.
[0250] As used herein, "optimized resistance to NH.sub.4.sup.+"
refers to an ability to grow in conditions of greater than 50, 75,
100, 125, 150, 175, 200, 225, 250, 275, or 300 mM NH.sub.3 or
NH.sub.4.sup.+ for at least about 24 or 48 hours. In an embodiment,
an optimized resistance to NH.sub.4.sup.+ refers to the ability to
grow at least 10, 20, 30, 40, or 50% more rapidly, or at least 10,
20, 30, 40, or 50% longer, in the presence of a selected
concentration of NH.sub.3 or NH.sub.4.sup.+ than can a naturally
occurring N. eutropha.
[0251] As used herein with respect to a comparison between nucleic
acid or protein sequences, "similar" means having homology. A
similar gene or protein may comprise, e.g., substitutions (such as
conservative or non-conservative substitutions), insertions (e.g.,
of at least 1, 2, 3, 4, 5, 10, 15, 20, 25, 30 amino acids, and for
example up to 2, 3, 4, 5, 10, 15, 20, 25, 30, or 50 amino acids, or
any positive combination thereof, or the number of nucleotides
necessary to encode said amino acids), or deletions (e.g., of at
least 1, 2, 3, 4, 5, 10, 15, 20, 25, 30 amino acids, and for
example up to 2, 3, 4, 5, 10, 15, 20, 25, 30, or 50 amino acids, or
any positive combination thereof, or the number of nucleotides
necessary to encode said amino acids), or any combination thereof.
Each of substitutions, insertions, and deletions may be positioned
at the N-terminus, C-terminus, or a central region of the protein
or gene. In embodiments, a conservative substitution is one that
does not alter the charge and/or polarity and/or approximate size
and/or geometry at the substituted position.
[0252] As used herein, "transgenic" means comprising one or more
exogenous portions of DNA. The exogenous DNA is derived from
another organism, e.g., another bacterium, a bacteriophage, an
animal, or a plant.
[0253] As used herein, treatment of a disease or condition refers
to reducing the severity or frequency of at least one symptom of
that disease or condition, compared to a similar but untreated
patient. Treatment can also refer to halting, slowing, or reversing
the progression of a disease or condition, compared to a similar
but untreated patient. Treatment may comprise addressing the root
cause of the disease and/or one or more symptoms.
[0254] As used herein a therapeutically effective amount refers to
a dose sufficient to prevent advancement, or to cause regression of
a disease or condition, or which is capable of relieving a symptom
of a disease or condition, or which is capable of achieving a
desired result. A therapeutically effective dose can be measured,
for example, as a number of bacteria or number of viable bacteria
(e.g., in CFUs) or a mass of bacteria (e.g., in milligrams, grams,
or kilograms), or a volume of bacteria (e.g., in mm.sup.3).
[0255] As used herein, the term "viability" refers to the
autotrophic bacteria's, e.g., ammonia oxidizing bacteria's, ability
to oxidize ammonia, ammonium, or urea to nitrite at a
pre-determined rate. In some embodiments, the rate refers to the
conversion of ammonium ions (NH.sub.4.sup.+) (e.g., at about 200
mM) to nitrite (NO.sub.2.sup.-) at a rate of at least 50, 75, 125,
or 150 micromoles NO.sub.2.sup.- per minute, e.g., about 100-150,
75-175, 75-125, 100-125, 125-150, or 125-175 micromoles/minute,
e.g., about 125 micromoles NO.sub.2.sup.- per minute.
[0256] "Growth media" or "AOB media," as referred to herein
comprises the following components of Table 3 or Table 4
herein.
[0257] In some embodiments, the states most relevant to the present
disclosure are the state of growth, e.g., maximal growth,
characterized by a pH of at least about 7.6, ammonia, trace
minerals, oxygen and carbon dioxide. Another state may be
characterized by a pH of about 7.4 or less and characterized by an
absence of carbon dioxide. Under low carbon dioxide conditions,
ammonia oxidizing bacteria, e.g., Nitrosomonas, continues to
oxidize ammonia into nitrite and generates ATP, but lacking carbon
dioxide, e.g., lacking sufficient carbon dioxide, to fix and
generate protein, it instead generates polyphosphate, which it uses
as an energy storage medium. This may allow the ammonia oxidizing
bacteria to remain in a "storage state" for a period of time, e.g.,
a pre-determined period of time, for example, at least 1, 2, 3, 4,
5, 6, 7, days, 1, 2, 3, 4 weeks, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11,
12 months, 1, 2, 3, 4, or 5 years. In some embodiments, the ammonia
oxidizing bacteria may remain in a storage state for at least about
6 months to about 1 year.
[0258] As used herein, "growth state" refers to autotrophic
bacteria, e.g., ammonia oxidizing bacteria, in a state or in an
environment, e.g., a media, e.g., a culture media, e.g., a growth
media, that may have a pH of at least about 7.6. Levels of at least
one of ammonia, ammonium ions, and urea may be between about 1
micromolar and 1000 millimolar. Levels of trace materials are
between about 0.01 micromolar iron and 200 micromolar iron. Levels
of oxygen are between about 5% and 100% oxygen saturation (e.g., of
media). Levels of carbon dioxide are between about 20 ppm and 10%
saturation (e.g., of media). In certain aspects, levels of at least
one of ammonia, ammonium ions, and urea may be between about 10
micromolar and 100 millimolar. Levels of trace materials are
between about 0.1 micromolar iron and 20 micromolar iron. Levels of
oxygen are between about 5% and 100% oxygen saturation. Levels of
carbon dioxide are between about 200 ppm and 5% saturation (e.g.,
of media).
[0259] As used herein, "polyphosphate loading state" refers to
autotrophic bacteria, e.g., ammonia oxidizing bacteria, in a state
or in an environment, e.g., a media, e.g., a culture media, e.g., a
growth media, that may have a pH of about 7.4, or less. Levels of
at least one of ammonia, ammonium ions, and urea are between about
1 micromolar and 2000 millimolar. Levels of trace materials are
between 0.01 micromolar iron and 200 micromolar iron. Levels of
oxygen are between about 0% and 100% 02 saturation (e.g., of
media). Levels of carbon dioxide are between/less than about zero
and 400 ppm, and phosphate levels greater than about 1 micromolar.
In certain aspects, levels of at least one of ammonia, ammonium
ions, and urea are between about 10 micromolar and 200 millimolar.
Levels of trace materials are between 0.1 micromolar iron and 20
micromolar iron. Levels of oxygen are between about 5% and 100% 02
saturation. Levels of carbon dioxide are between/less than about
zero and 200 ppm, and phosphate levels greater than about 10
micromolar.
[0260] The polyphosphate loading state may be induced for a period
of time, e.g., a pre-determined period of time. The pre-determined
period of time may the time period that allows sufficient
polyphosphate accumulation in the ammonia oxidizing bacteria. This
pre-determined period of time is the period of time suitable to
provide for sufficient polyphosphate loading to allow for the
ammonia oxidizing bacteria to be stored for an extended period of
time. The pre-determined period of time may be at least partially
based on a period of time of about 0.2-10 times, 0.3-5 times, 0.5-3
times, 0.5-1.5 times, or 0.5 to 1 times the doubling time for the
ammonia oxidizing bacteria. The pre-determined period of time may
be at least partially based on a period of time of about one
doubling time for the ammonia oxidizing bacteria. In some
embodiments, the pre-determined period of time is between about 8
hours and 12 hours. In some embodiments, the pre-determined period
of time is about 10 hours. In some embodiments, the pre-determined
period of time is about 24 hours.
[0261] A purpose of the polyphosphate loading state may be to
provide AOB with sufficient ammonia, ammonium ions, and/or urea,
and O.sub.2 such that ATP can be produced, but to deny them
CO.sub.2 and carbonate such that they are unable to use that ATP to
fix CO.sub.2 and instead use that ATP to generate polyphosphate
which may be stored by the bacteria.
[0262] As used herein, the term "storage state" refers to
autotrophic bacteria, e.g., ammonia oxidizing bacteria, in a state
or in an environment, e.g., a media, e.g., a culture media, e.g., a
growth media, having a pH of about 7.4 or less (in some
embodiments, the pH may be 7.6 or less). Levels of at least one of
ammonia, ammonium ions, and urea are between about _1 and 1000
micromolar. Levels of trace materials are between about 0.1 and 100
micromolar. Levels of oxygen are between about 0 and 100%
saturation (e.g., of media). Levels of carbon dioxide are between
about 0 and 800 ppm. In certain aspects, levels of at least one of
ammonia, ammonium ions, and urea are between about _10 and 100
micromolar. Levels of trace materials are between about 1 and 10
micromolar. Levels of oxygen are between about 0 and 100%
saturation (e.g., of media). Levels of carbon dioxide are between
about 0 and 400 ppm.
[0263] AOB are produced according to some embodiments of the
present disclosure by generating AOB biomass during a growth state,
then exposing the AOB to a polyphosphate loading state and then
removing the media and resuspending the AOB in a buffer, e.g., a
storage buffer (i.e., the storage state).
[0264] The ammonia oxidizing bacteria may remain in a "storage
state" for a period of time, e.g., a pre-determined period of time,
for example, at least 1, 2, 3, 4, 5, 6, 7, days, 1, 2, 3, 4 weeks,
1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 months, 1, 2, 3, 4, or 5
years. In some embodiments, the ammonia oxidizing bacteria may
remain in a storage state for at least about 6 months to about 1
year. Upon revival, the viability of the ammonia oxidizing bacteria
is at least about 50%, 60%, 70%, 80%, 90%, or 100% of the viability
as of the ammonia oxidizing bacteria prior to storage e.g., in a
growth state). In some embodiments, the preparation of ammonia
oxidizing bacteria may be prepared, such that no more than 10%,
20%, 30%, 40%, 50%, 60%, or 70% of the ability to oxidize
NH.sub.4.sup.+ is lost upon storage at selected conditions.
[0265] The time that it takes to revive the ammonia oxidizing
bacteria from a storage state (or a polyphosphate loading state)
may be a pre-determined period of time. For example, the
pre-determined period of time may be less than about 75 hours, or
less than about 72 hours. The pre-determined period of time may at
least partially based on a period time of about 0.2-10 times, 0.3-5
times, 0.5-3 times, 0.5-1.5 times, or 0.5 to 1 times the doubling
time for the ammonia oxidizing bacteria. The pre-determined period
of time may be at least partially based on a period of time of
about one doubling time for the ammonia oxidizing bacteria. The
pre-determined period of time may be between about 8 hours and 12
hours. The pre-determined period of time may be about 10 hours. The
pre-determined time may be less than about 75 hours, 72 hours, 70
hours, 68 hours, 65 hours, 60 hours, 55 hours, 50 hours, 45 hours,
40 hours, 35 hours, 30 hours, 25 hours, 20 hours, 15 hours, 10
hours, 5 hours, 4 hours, 3, hours, 2 hours, or 1 hour. The
pre-determined period of time may be between about 5 minutes and 5
hours. The pre-determined period of time may be about 5-10 minutes,
10-15 minutes, 15-20 minutes, 20-25 minutes, 25-30 minutes, 30-45
minutes, 45-60 minutes, 60 minutes-1.5 hours, 1.5 hours-2 hours, 2
hours-2.5 hours, 2.5 hours-3 hours, 3 hours-3.5 hours, 3.5 hours-4
hours, 4 hours-4.5 hours, 4.5 hours-5 hours. In some embodiments,
the pre-determined period of time may be about 2 hours. The
pre-determined period of time, e.g., may be the time it may take to
achieve revival of the ammonia oxidizing bacteria, e.g., achieve
viability of the ammonia oxidizing bacteria as compared to the
viability of the bacteria prior to storage (e.g., in a growth
state), e.g., at least about 10%, 20%, 30%, 40%, 50%, 60%, 70%,
80%, 90%, 95%, 97%, 98%, 99%, or 100% viability.
2. AMMONIA OXIDIZING BACTERIA (AOBS), N. EUTROPHA STRAIN D23 AND
SIMILAR BACTERIA
[0266] Autotrophic ammonia oxidizing bacteria, which may be
referred to herein as AOBs or AOB, are obligate autotrophic
bacteria as noted by Alan B. Hooper and A. Krummel at al. Alan B.
Hooper, Biochemical Basis of Obligate Autotrophy in Nitrosomonas
europaea, Journal of Bacteriology, February 1969, p. 776-779. Antje
Krummel et al., Effect of Organic Matter on Growth and Cell Yield
of Ammonia-Oxidizing Bacteria, Arch Microbiol (1982) 133: 50-54.
These bacteria derive all metabolic energy only from the oxidation
of ammonia to nitrite with nitric oxide (NO) as an intermediate
product in their respiration chain and derive virtually all carbon
by fixing carbon dioxide. They are incapable of utilizing carbon
sources other than a few simple molecules.
[0267] Ammonia oxidizing bacteria (AOB) are widely found in the
environment, and in the presence of ammonia, oxygen and trace
metals will fix carbon dioxide and proliferate. AOB may be slow
growing and toxic levels of ammonia may kill fish and other
organisms before AOB can proliferate and reduce ammonia to
non-toxic levels. Slow growth of AOB also may delay the health
benefits of the NO and nitrite the AOB produce when applied to the
skin.
[0268] Supplementing the aquarium, skin, or process with sufficient
viable AOB grown and stored for that purpose is desired. AOB do not
form spores, so storage in the dry state with high viability is
difficult, and storage in the wet state leaves them metabolically
active. Decay of nitrifying capacity during storage of AOB for
wastewater treatment has been studied, as for example (Munz G,
Lubello C, Oleszkiewicz J A. Modeling the decay of ammonium
oxidizing bacteria. Water Res. 2011 January; 45(2): 557-64. Oi:
10.1016/j.watres.2010.09.022.)
[0269] Growth, prolonged storage, and restoration of activity of
Nitrosomonas is discussed by Cassidy et al. (U.S. Pat. No.
5,314,542) where they disclose growing Nitrosomonas, removing toxic
waste products, storing in sterile water of appropriate salinity
for periods of time up to one year, and then reviving by adding
buffer (CaCO.sub.3) and 200 ppm, of ammonium, which reviving takes
72 hours.
[0270] As obligate autotrophs, AOB synthesize protein via the
fixing of CO.sub.2 using the energy and reducing equivalents
generated by the oxidation of ammonia to nitrite. Growth requires
ammonia, oxygen, minerals and carbon dioxide.
[0271] Nitrosomonas may exist in several metabolic states,
according to "Polyphosphate and Orthophosphate Content of
Nitrosomonas europaea as a Function of Growth" by K. R. Terry and
A. B. Hooper, Journal of Bacteriology, July 1970, p. 199-206, Vol.
103, No. I.
[0272] In certain embodiments of the disclosure, the ammonia
oxidizing bacteria may be axenic. The preparation (formulation or
composition) of ammonia oxidizing bacteria may comprise, consist
essentially of, or consist of axenic ammonia oxidizing bacteria.
The ammonia oxidizing bacteria may be from a genus selected from
the group consisting of Nitrosomonas, Nitrosococcus, Nitrosospria,
Nitrosocystis, Nitrosolobus, Nitrosovibrio, and combinations
thereof.
[0273] This disclosure provides, inter alia, N. eutropha strain
D23, a unique, e.g., optimized strain of ammonia oxidizing bacteria
that can increase production of nitric oxide and nitric oxide
precursors on the surface of a subject, e.g., a human subject. This
disclosure also provides methods of using the bacteria and articles
comprising the bacteria.
[0274] In embodiments, the N. eutropha is non-naturally occurring.
For instance, it may have accumulated desirable mutations during a
period of selection. In other embodiments, desirable mutations may
be introduced by an experimenter. In some embodiments, the N.
eutropha may be a purified preparation, and may be an optimized N.
eutropha.
[0275] In preferred embodiments, the N. eutropha strain is
autotrophic and so incapable of causing infection. A preferred
strain utilizes urea as well as ammonia, so that hydrolysis of the
urea in sweat would not be necessary prior to absorption and
utilization by the bacteria. Also, in order to grow at low pH, the
bacteria may either absorb NH.sub.4.sup.+ ions or urea. The
selected strain should also be capable of living on the external
skin of a subject, e.g., a human, and be tolerant of conditions
there.
[0276] Although this disclosure refers to N. eutropha strain D23 in
detail, the preparations, methods, compositions, treatments,
wearable articles, and articles of clothing may be used with one or
more of: one or more other strains of N. eutropha, one or more
other species of Nitrosomonas, and one or more other ammonia
oxidizing bacteria. Autotrophic AOBs are obligate autotrophic
bacteria as noted by Alan B. Hooper and A. Krummel at al. Alan B.
Hooper, Biochemical Basis of Obligate Autotrophy in Nitrosomonas
europaea, Journal of Bacteriology, February 1969, p. 776-779. Antje
Krummel et al., Effect of Organic Matter on Growth and Cell Yield
of Ammonia-Oxidizing Bacteria, Arch Microbiol (1982) 133: 50-54.
These bacteria derive all metabolic energy only from the oxidation
of ammonia to nitrite with nitric oxide (NO) as an intermediate
product in their respiration chain and derive virtually all carbon
by fixing carbon dioxide. They are incapable of utilizing carbon
sources other than a few simple molecules.
[0277] In certain embodiments, the N. eutropha is the strain
deposited with the American Tissue Culture Collection (ATCC) on
Apr. 8, 2014, designated AOB D23-100 (25 vials) under accession
number PTA-121157.
[0278] In certain embodiments, the N. eutropha comprises a
chromosome having a sequence at least 70%, 80%, 85%, 90%, 95%, 96%,
97%, 98%, 99%, or 99.5% identical to SEQ ID NO: 1 (the strain D23
whole-genome sequence).
[0279] In certain embodiments, a bacterium with the above-mentioned
sequence characteristics has one or more of (1) an optimized growth
rate as measured by doubling time, (2) an optimized growth rate as
measured by OD600, (3) an optimized NH.sub.4.sup.+ oxidation rate,
(4) an optimized resistance to NH.sub.4.sup.+, and (4) an optimized
resistance to NO.sub.2.sup.-. Particular sub-combinations of these
properties are specified in the following paragraph.
[0280] In some embodiments, the N. eutropha described herein has
one or more of: (1) an optimized growth rate as measured by
doubling time, (2) an optimized growth rate as measured by OD600,
(3) an optimized NH.sub.4.sup.+ oxidation rate, (4) an optimized
resistance to, NH.sub.4.sup.+, and (4) an optimized resistance to,
NO.sub.2.sup.-. For instance, the bacterium may have properties (1)
and (2); (2) and (3); (3) and (4); or (4) and (5) from the list at
the beginning of this paragraph. As another example, the bacterium
may have properties (1), (2), and (3); (1), (2), and (4); (1), (2),
and (5); (1), (3), and (4); (1), (3), and (5); (1), (4), and (5);
(2), (3), and (4); (2), (3), and (5), or (3), (4), and (5) from the
list at the beginning of this paragraph. As a further example, the
bacterium may have properties (1), (2), (3), and (4); (1), (2),
(3), and (5); (1), (2), (4), and (5); (1), (3), (4), and (5); or
(2), (3), (4), and (5) from the list at the beginning of this
paragraph. In some embodiments, the bacterium has properties (1),
(2), (3), (4), and (5) from the list at the beginning of this
paragraph.
[0281] This disclosure also provides an axenic composition of N.
eutropha having one or more of: (1) an optimized growth rate as
measured by doubling time, (2) an optimized growth rate as measured
by OD600, (3) an optimized NH.sub.4.sup.+ oxidation rate, (4) an
optimized resistance to, NH.sub.4.sup.+, and (4) an optimized
resistance to, NO.sub.2.sup.-. For instance, the axenic N. eutropha
composition may have properties (1) and (2); (2) and (3); (3) and
(4); or (4) and (5) from the list at the beginning of this
paragraph. As another example, the axenic N. eutropha composition
may have properties (1), (2), and (3); (1), (2), and (4); (1), (2),
and (5); (1), (3), and (4); (1), (3), and (5); (1), (4), and (5);
(2), (3), and (4); (2), (3), and (5), or (3), (4), and (5) from the
list at the beginning of this paragraph. As a further example, the
axenic N. eutropha composition may have properties (1), (2), (3),
and (4); (1), (2), (3), and (5); (1), (2), (4), and (5); (1), (3),
(4), and (5); or (2), (3), (4), and (5) from the list at the
beginning of this paragraph. In some embodiments, the axenic N.
eutropha composition has properties (1), (2), (3), (4), and (5)
from the list at the beginning of this paragraph.
[0282] N. eutropha strain D23, as deposited in the form of 25 vials
on Apr. 8, 2014, in the ATCC patent depository, designated AOB
D23-100, under accession number PTA-121157, comprises a circular
genome having SEQ ID NO: 1 or its complement. Accordingly, in some
embodiments, an N. eutropha strain described herein comprises a
nucleic acid sequence, e.g., a genome, that is similar to SEQ ID
NO: 1 or its complement.
[0283] For instance, the N. eutropha may comprise a nucleic acid
sequence having a 1,000 base pair portion having at least about
80%, 85%, 90%, 95%, 97%, 98%, 99%, or 99.5% identity to a 1,000
base pair portion of SEQ ID NO: 1 or its complement. The 1,000 base
pair portion may span, e.g., nucleotides (n*1,000)+1 to
(n+1)*1,000, where n=0, 1, 2, 3 . . . 2538, e.g., nucleotides
1-1,000, 1,001-2,000, and so on through the end of SEQ ID NO:
1.
[0284] In embodiments, the N. eutropha comprises a nucleic acid
sequence having a 2,000 base pair portion having at least about
80%, 85%, 90%, 95%, 97%, 98%, 99%, or 99.5% identity to a 2,000
base pair portion of SEQ ID NO: 1 or its complement. The 2,000 base
pair portion may span, e.g., nucleotides (n*2,000)+1 to
(n+1)*2,000, where n=0, 1, 2, 3 . . . 1269, e.g., nucleotides
1-2,000, 2,001-4,000, and so on through the end of SEQ ID NO:
1.
[0285] In embodiments, the N. eutropha comprises a nucleic acid
sequence having a 5,000 base pair portion having at least about
80%, 85%, 90%, 95%, 97%, 98%, 99%, or 99.5% identity to a 5,000
base pair portion of SEQ ID NO: 1 or its complement. The 5,000 base
pair portion may span, e.g., nucleotides (n*5,000)+1 to
(n+1)*5,000, where n=0, 1, 2, 3 . . . 508, e.g., nucleotides
1-5,000, 5,001-10,000, and so on through the end of SEQ ID NO:
1.
[0286] In embodiments, the N. eutropha comprises a nucleic acid
sequence having a 10,000 base pair portion having at least about
80%, 85%, 90%, 95%, 97%, 98%, 99%, or 99.5% identity to a 10,000
base pair portion of SEQ ID NO: 1 or its complement. The 10,000
base pair portion may span, e.g., nucleotides (n*10,000)+1 to
(n+1)*10,000, where n=0, 1, 2, 3 . . . 254, e.g., nucleotides
1-10,000, 10,001-20,000, and so on through the end of SEQ ID NO:
1.
[0287] In embodiments, the N. eutropha comprises a nucleic acid
sequence having a 20,000 base pair portion having at least about
80%, 85%, 90%, 95%, 97%, 98%, 99%, or 99.5% identity to a 20,000
base pair portion of SEQ ID NO: 1 or its complement. The 20,000
base pair portion may span, e.g., nucleotides (n*20,000)+1 to
(n+1)*20,000, where n=0, 1, 2, 3 . . . 127, e.g., nucleotides
1-20,000, 20,001-40,000, and so on through the end of SEQ ID NO:
1.
[0288] In embodiments, the N. eutropha comprises a nucleic acid
sequence having a 50,000 base pair portion having at least about
80%, 85%, 90%, 95%, 97%, 98%, 99%, or 99.5% identity to a 50,000
base pair portion of SEQ ID NO: 1 or its complement. The 50,000
base pair portion may span, e.g., nucleotides (n*50,000)+1 to
(n+1)*50,000, where n=0, 1, 2, 3 . . . 51, e.g., nucleotides
1-50,000, 50,001-100,000, and so on through the end of SEQ ID NO:
1.
[0289] In embodiments, the N. eutropha comprises a nucleic acid
sequence having a 100,000 base pair portion having at least about
80%, 85%, 90%, 95%, 97%, 98%, 99%, or 99.5% identity to a 100,000
base pair portion of SEQ ID NO: 1 or its complement. The 100,000
base pair portion may span, e.g., nucleotides (n*100,000)+1 to
(n+1)*100,000, where n=0, 1, 2, 3 . . . 26, e.g., nucleotides
1-100,000, 100,001-20,000, and so on through the end of SEQ ID NO:
1.
[0290] In some aspects, the present disclosure provides a
composition of N. eutropha comprising a chromosome at least about
70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 99.5% identical to
SEQ ID NO: 1. In some aspects, the present disclosure provides an
axenic composition of N. eutropha comprising a chromosome at least
about 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 99.5%
identical to SEQ ID NO: 1.
[0291] In certain embodiments, the N. eutropha strain comprises a
nucleic acid sequence, e.g., a genome, that hybridizes to SEQ ID
NO: 1, or to the genome of the D23 strain deposited in the form of
25 vials with the ATCC patent depository on Apr. 8, 2014,
designated AOB D23-100, under accession number PTA-121157, or their
complements, under low stringency, medium stringency, high
stringency, or very high stringency, or other hybridization
condition described herein. As used herein, the term "hybridizes
under low stringency, medium stringency, high stringency, or very
high stringency conditions" describes conditions for hybridization
and washing. Guidance for performing hybridization reactions can be
found in Current Protocols in Molecular Biology, John Wiley &
Sons, N.Y. (1989), 6.3.1-6.3.6, which is incorporated by reference.
Aqueous and nonaqueous methods are described in that reference and
either can be used. Specific hybridization conditions referred to
herein are as follows: 1) low stringency hybridization conditions
in 6.times. sodium chloride/sodium citrate (SSC) at about
45.degree. C., followed by two washes in 0.2.times.SSC, 0.1% SDS at
least at 50.degree. C. (the temperature of the washes can be
increased to 55.degree. C. for low stringency conditions); 2)
medium stringency hybridization conditions in 6.times.SSC at about
45.degree. C., followed by one or more washes in 0.2.times.SSC,
0.1% SDS at 60.degree. C.; 3) high stringency hybridization
conditions in 6.times.SSC at about 45.degree. C., followed by one
or more washes in 0.2.times.SSC, 0.1% SDS at 65.degree. C.; 4) very
high stringency hybridization conditions are 0.5M sodium phosphate,
7% SDS at 65.degree. C., followed by one or more washes at
0.2.times.SSC, 1% SDS at 65.degree. C. Very high stringency
conditions (4) are suitable conditions and the ones that should be
used unless otherwise specified.
[0292] The genome of strain D23 (SEQ ID NO: 1) was compared with
the genome of N. eutropha C91. An annotation of the D23 genome is
shown in Supplementary Table 1, which lists the positions of 2,777
genes in SEQ ID NO: 1 as identified by sequence analysis. In
certain embodiments, the N. eutropha described herein comprises one
or more genes or proteins listed in Supplementary Table 1, or a
gene or protein similar to one of said genes or proteins.
[0293] Accordingly, in some embodiments, the N. eutropha comprises
a gene of Supplementary Table 1, or a protein encoded by said gene.
In certain embodiments, the N. eutropha comprises a gene that is
similar (e.g., at least 70%, 80%, 85%, 90%, 95%, 97%, 98%, 99%, or
99.5% identical) to a gene of Supplementary Table 1, or a protein
encoded by said gene. In embodiments, the N. eutropha comprises
genes or proteins that are identical or similar to at least 2, 3,
4, 5, 10, 20, 30, 40, 50, 100, 150, 200, 250, 300, 350, 400, 450,
500, 1000, 1500, 2000, 2500, or all the genes of Supplementary
Table 1, or a protein encoded by said genes.
[0294] In some embodiments, the N. eutropha described herein (e.g.,
strain D23) comprises one or more genes or proteins that are absent
from strain C91, or a gene or protein similar to one of said genes
or proteins. Examples of these genes are set out in FIG. 6-8 and
are described in more detail in Example 4 herein.
[0295] Accordingly, with respect to FIG. 6, in some embodiments,
the N. eutropha comprises genes that are identical or similar
(e.g., at least 70%, 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 99.5%
identical) to 1, 2, 3, 4, 5, 10, 15, 20, 30, 40, 50, 60, 70, 80,
90, 100, 110, 120, 130, 140, 150, 160, or all of the genes in FIG.
6. In some embodiments, the N. eutropha comprises proteins that are
identical or similar (e.g., at least 70%, 80%, 85%, 90%, 95%, 97%,
98%, 99%, or 99.5% identical) to 1, 2, 3, 4, 5, 10, 15, 20, 30, 40,
50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, or all of
the proteins encoded by the genes listed in FIG. 6.
[0296] With respect to FIG. 7, in some embodiments, the N. eutropha
comprises genes that are identical or similar (e.g., at least 70%,
80%, 85%, 90%, 95%, 97%, 98%, 99%, or 99.5% identical) to 1, 2, 3,
4, 5, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130,
140, 150, 160, or all of the genes in FIG. 7. In some embodiments,
the N. eutropha comprises proteins that are identical or similar
(e.g., at least 70%, 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 99.5%
identical) to 1, 2, 3, 4, 5, 10, 15, 20, 30, 40, 50, 60, 70, 80,
90, 100, 110, 120, 130, 140, 150, 160, or all of the proteins
encoded by the genes listed in FIG. 7.
[0297] With respect to FIG. 8, in some embodiments, the N. eutropha
comprises genes that are identical or similar (e.g., at least 70%,
80%, 85%, 90%, 95%, 97%, 98%, 99%, or 99.5% identical) to 1, 2, 3,
4, 5, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130,
140, 150, 200, or all of the genes in FIG. 8. In some embodiments,
the N. eutropha comprises proteins that are identical or similar
(e.g., at least 70%, 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 99.5%
identical) to 1, 2, 3, 4, 5, 10, 15, 20, 30, 40, 50, 60, 70, 80,
90, 100, 110, 120, 130, 140, 150, 200, or all of the proteins
encoded by the genes listed in FIG. 8.
[0298] With respect to FIGS. 6-8 collectively, in some embodiments,
the N. eutropha comprises genes that are identical or similar
(e.g., at least 70%, 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 99.5%
identical) to 1, 2, 3, 4, 5, 10, 20, 40, 60, 80, 100, 150, 200,
250, 300, 350, 400, 450, 500, or all of the genes in FIGS. 6-8. In
some embodiments, the N. eutropha comprises proteins that are
identical or similar (e.g., at least 70%, 80%, 85%, 90%, 95%, 97%,
98%, 99%, or 99.5% identical) to 1, 2, 3, 4, 5, 10, 20, 40, 60, 80,
100, 150, 200, 250, 300, 350, 400, 450, 500, or all of the proteins
encoded by genes listed in FIGS. 6-8.
[0299] In some embodiments, the N. eutropha described herein (e.g.,
strain D23) lacks one or more genes or proteins that are unique to
strain C91, or a gene or protein similar to one of said genes or
proteins. Examples of these genes are set out in FIG. 9 and are
described in more detail in Example 4 herein. Accordingly, in some
embodiments, the N. eutropha described herein lacks at least 1, 2,
3, 4, 5, 10, 20, 50, 100, 150, 200, 250, or all of the genes of
FIG. 9. In some embodiments, the N. eutropha described herein lacks
up to 2, 3, 4, 5, 10, 20, 50, 100, 150, 200, 250, or all of the
genes of FIG. 9. In embodiments, the N. eutropha described herein
lacks about 1-5, 5-10, 10-20, 20-50, 50-100, 100-150, 150-200,
200-250, or 250-all of the genes of FIG. 9.
[0300] Sequencing of the D23 genome revealed several genes of
potential interest, including genes involved in ammonia metabolism
(e.g., ammonia monooxygenase, hydroxylamine oxidoreductase,
cytochrome c554, and cytochrome c.sub.M552). All of these genes are
present in multiple copies, and in general the copies are not
identical to each other. One set of genes of interest is the
ammonia monooxygenase synthesis operon amoCAB, which is present in
two copies, along with a third copy of amoC. The operons have
homologs in C91, i.e., Neut_2078/7/6 and Neut_2319/8/7. Another set
of genes of interest is hydroxylamine oxidoreductase (hao), which
is present in three copies. The hao homologs in C91 are designated
Neut_1672, 1793, and 2335. A third set of genes of interest is the
cytochrome c554 gene encoded by cycA, which is present in three
copies. The corresponding C91 genes are designated Neut_1670, 1791,
and 2333. A fourth set of genes of interest is the cytochrome
c.sub.M552 genes encoded by cycB, which are present in two copies.
The homologous C91 genes are designated Neut_1790 and 2332. Each
group of genes is summarized in Table 1 and is discussed in more
detail below.
TABLE-US-00001 TABLE 1 Sequences of ammonia metabolism genes in N.
eutropha strain D23. SEQ ID in SEQ ID in strain D23 strain C91 Type
Gene name 1. ammonia monooxygenase 4 34 Protein amoC1 5 35 DNA
amoC1 6 36 Protein amoA1 7 37 DNA amoA1 8 38 Protein amoB1 9 39 DNA
amoB1 10 40 Protein amoC2 11 41 DNA amoC2 12 42 Protein amoA2 13 43
DNA amoA2 14 44 Protein amoB2 15 45 DNA amoB2 16 46 Protein amoC3
17 47 DNA amoC3 2. hydroxylamine oxidoreductase 18 48 Protein hao1
19 49 DNA hao1 20 50 Protein hao2 21 51 DNA hao2 22 52 Protein hao3
23 53 DNA hao3 3. cytochrome c554 24 54 Protein c554 cycA1 25 55
DNA c554 cycA1 26 56 Protein c554 cycA2 27 57 DNA c554 cycA2 28 58
Protein c554 cycA3 29 59 DNA c554 cycA3 4. cytochrome c.sub.M552 30
60 Protein c.sub.M552 cycB1 31 61 DNA c.sub.M552 cycB1 32 62
Protein c.sub.M552 cycB2 33 63 DNA c.sub.M552 cycB2
[0301] In some aspects, the N. eutropha described herein comprises
genes identical to or similar to the genes and proteins of Table
1.
[0302] More particularly, in certain aspects, this disclosure
provides a composition of N. eutropha, e.g., a purified preparation
of N. eutropha comprising a nucleic acid sequence at least about
70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 99.5% identical to
an ammonia monooxygenase sequence of Table 1. In certain aspects,
this disclosure provides a composition of N. eutropha comprising a
nucleic acid sequence at least about 70%, 80%, 85%, 90%, 95%, 96%,
97%, 98%, 99%, or 99.5% identical to a hydroxylamine oxidoreductase
sequence of Table 1. In certain aspects, this disclosure provides a
composition of N. eutropha comprising a nucleic acid sequence at
least about 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 99.5%
identical to a cytochrome c554 sequence of Table 1. In certain
aspects, this disclosure provides a composition of N. eutropha
comprising nucleic acid sequences at least about 70%, 80%, 85%,
90%, 95%, 96%, 97%, 98%, 99%, or 99.5% identical to a cytochrome
c.sub.M552 sequence of Table 1.
[0303] In certain aspects, this disclosure provides a composition
of N. eutropha comprising an amino acid sequence at least about
70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.2%, 99.3%, 99.4%,
99.5%, or 99.6% identical to an ammonia monooxygenase sequence of
Table 1. In certain aspects, this disclosure provides a composition
of N. eutropha comprising an amino acid sequence at least about
70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.4%, 99.5%, 99.6%,
or 99.7% identical to hydroxylamine oxidoreductase sequence of
Table 1. In certain aspects, this disclosure provides a composition
of N. eutropha comprising an amino acid sequence at least about
70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.1%, 99.2%, 99.3%,
99.5%, 99.6%, or 99.7% identical to a cytochrome c554 sequence of
Table 1. In certain aspects, this disclosure provides a composition
of N. eutropha comprising amino acid sequences at least about 70%,
80%, 85%, 90%, 95%, 96%, 97%, 97.1%, 97.2%, 97.5%, 98%, 98.5%,
98.6%, 98.7%, 98.8%, 99%, or 99.5% identical to a cytochrome
c.sub.M552 sequence of Table 1.
[0304] In some embodiments, the N. eutropha are present in an
axenic composition, and e.g., in the form of a purified preparation
of optimized N. eutropha.
[0305] More particularly, in certain aspects, this disclosure
provides an axenic composition of N. eutropha comprising a nucleic
acid sequence at least about 70%, 80%, 85%, 90%, 95%, 96%, 97%,
98%, 98.5%, 98.8%, 98.9%, 99%, 99.2%, 99.3%, 99.4%, 99.5%, or 99.6%
identical to an ammonia monooxygenase sequence of Table 1. In
certain aspects, this disclosure provides an axenic composition of
N. eutropha comprising a nucleic acid sequence at least about 70%,
80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 99.5% identical to a
hydroxylamine oxidoreductase sequence of Table 1. In certain
aspects, this disclosure provides an axenic composition of N.
eutropha comprising a nucleic acid sequence at least about 70%,
80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 99.5% identical to a
cytochrome c554 sequence of Table 1. In certain aspects, this
disclosure provides an axenic composition of N. eutropha comprising
nucleic acid sequences at least about 70%, 80%, 85%, 90%, 95%, 96%,
97%, 98%, 99%, or 99.5% identical to a cytochrome c.sub.M552
sequence of Table 1.
[0306] In certain aspects, this disclosure provides an axenic
composition of N. eutropha comprising an amino acid sequence at
least about 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 98.5%, 98.8%,
98.9%, 99%, 99.2%, 99.3%, 99.4%, 99.5%, or 99.6% identical to an
ammonia monooxygenase sequence of Table 1. In certain aspects, this
disclosure provides an axenic composition of N. eutropha comprising
an amino acid sequence at least about 70%, 80%, 85%, 90%, 95%, 96%,
97%, 98%, 99%, 99.4%, 99.5%, 99.6%, or 99.7% identical to
hydroxylamine oxidoreductase sequence of Table 1. In certain
aspects, this disclosure provides an axenic composition of N.
eutropha comprising an amino acid sequence at least about 70%, 80%,
85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.1%, 99.2%, 99.3%, 99.5%,
99.6%, or 99.7% identical to a cytochrome c554 sequence of Table 1.
In certain aspects, this disclosure provides an axenic composition
of N. eutropha comprising amino acid sequences at least about 70%,
80%, 85%, 90%, 95%, 96%, 97%, 97.1%, 97.2%, 97.5%, 98%, 98.5%,
98.6%, 98.7%, 98.8%, 99%, or 99.5% identical to a cytochrome
c.sub.M552 sequence of Table 1.
[0307] In some embodiments, the N. eutropha comprises a gene or
protein comprising a sequence at least about 70%, 80%, 85%, 90%,
95%, 96%, 97%, 98%, 99%, or 99.5% identical to a strain D23
sequence of Table 1, e.g., any of SEQ IDs 4-33. Substitutions may
be conservative or non-conservative; also, insertions and deletions
are contemplated. In some embodiments, the N. eutropha comprises a
gene or protein comprising a sequence of Table 1, e.g., any of SEQ
IDs 4-33. In some embodiments, the protein has an N-terminal and/or
C-terminal extension or deletion of up to about 1, 2, 3, 4, 5, 6,
8, 10, 15, 20, 25, 50, or 100 amino acids.
[0308] Alignment of the nucleic acid sequences of Table 1 shows the
percent identity between homologs in C91 and D23. The following
paragraphs discuss this percent identity and describe various genes
having homology to the D23 genes of Table 1.
[0309] More specifically, the amoA1 genes are about 98.8% identical
(i.e., at 821/831 positions). Accordingly, in some embodiments, the
N. eutropha described herein comprise D23 nucleotides at at least
1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or all of the positions that differ
in this gene between strains C91 and D23. In embodiments, the N.
eutropha described herein comprise D23 nucleotides at at most 1, 2,
3, 4, 5, 6, 7, 8, 9, 10, or all of the positions that differ in
this gene between strains C91 and D23. In embodiments, the N.
eutropha described herein comprise a gene at least about 98.8%,
98.9%, 99.0%, 99.2%, 99.4%, 99.6%, 99.8%, or 100% identical to the
D23 amoA1 gene.
[0310] The amoA2 genes are about 98.8% identical (i.e., at 821/831
positions). Accordingly, in some embodiments, the N. eutropha
described herein comprise D23 nucleotides at at least 1, 2, 3, 4,
5, 6, 7, 8, 9, 10, or all of the positions that differ in this gene
between strains C91 and D23. In embodiments, the N. eutropha
described herein comprise D23 nucleotides at at most 1, 2, 3, 4, 5,
6, 7, 8, 9, 10, or all of the positions that differ in this gene
between strains C91 and D23. In embodiments, the N. eutropha
described herein comprise a gene at least about 98.8%, 98.9%,
99.0%, 99.2%, 99.4%, 99.6%, 99.8%, or 100% identical to the D23
amoA2 gene.
[0311] The amoB1 genes are about 99.1% identical (i.e., at
1255/1266 positions). Accordingly, in some embodiments, the N.
eutropha described herein comprise D23 nucleotides at at least 1,
2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or all of the positions that differ
in this gene between strains C91 and D23. In embodiments, the N.
eutropha described herein comprise D23 nucleotides at at most 1, 2,
3, 4, 5, 6, 7, 8, 9, 10, 11, or all of the positions that differ in
this gene between strains C91 and D23. In embodiments, the N.
eutropha described herein comprise a gene at least about 99.1%,
99.2%, 99.4%, 99.6%, 99.8%, or 100% identical to the D23 amoB1
gene.
[0312] The amoB2 genes are about 99.1% identical (i.e., at
1254/1266 positions). Accordingly, in some embodiments, the N.
eutropha described herein comprise D23 nucleotides at at least 1,
2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or all of the positions that
differ in this gene between strains C91 and D23. In embodiments,
the N. eutropha described herein comprise D23 nucleotides at at
most 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or all of the positions
that differ in this gene between strains C91 and D23. In
embodiments, the N. eutropha described herein comprise a gene at
least about 99.1%, 99.2%, 99.4%, 99.6%, 99.8%, or 100% identical to
the D23 amoB2 gene.
[0313] The amoC1 genes are about 99.8% identical (i.e., at 814/816
positions). Accordingly, in some embodiments, the N. eutropha
described herein comprise D23 nucleotides at at least 1, 2, or all
of the positions that differ in this gene between strains C91 and
D23. In embodiments, the N. eutropha described herein comprise D23
nucleotides at at most 1, 2, or all of the positions that differ in
this gene between strains C91 and D23. In embodiments, the N.
eutropha described herein comprise a gene at least about 99.8%,
99.9%, or 100% identical to the D23 amoC1 gene.
[0314] The amoC2 genes are about 99.8% identical (i.e., at 814/816
positions). Accordingly, in some embodiments, the N. eutropha
described herein comprise D23 nucleotides at at least 1, 2, or all
of the positions that differ in this gene between strains C91 and
D23. In embodiments, the N. eutropha described herein comprise D23
nucleotides at at most 1, 2, or all of the positions that differ in
this gene between strains C91 and D23. In embodiments, the N.
eutropha described herein comprise a gene at least about 99.8%,
99.9%, or 100% identical to the D23 amoC2 gene.
[0315] The amoC3 genes are about 98.9% identical (i.e., at 816/825
positions). Accordingly, in some embodiments, the N. eutropha
described herein comprise D23 nucleotides at at least 1, 2, 3, 4,
5, 6, 7, 8, 9, or all of the positions that differ in this gene
between strains C91 and D23. In embodiments, the N. eutropha
described herein comprise D23 nucleotides at at most 1, 2, 3, 4, 5,
6, 7, 8, 9, or all of the positions that differ in this gene
between strains C91 and D23. In embodiments, the N. eutropha
described herein comprise a gene at least about 98.9%, 99.0%,
99.2%, 99.4%, 99.6%, 99.8%, or 100% identical to the D23 amoC3
gene.
[0316] The hao1 genes are about 99.0% identical (i.e., at 1696/1713
positions). Accordingly, in some embodiments, the N. eutropha
described herein comprise D23 nucleotides at at least 1, 2, 3, 4,
5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, or all of the
positions that differ in this gene between strains C91 and D23. In
embodiments, the N. eutropha described herein comprise D23
nucleotides at at most 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13,
14, 15, 16, 17, or all of the positions that differ in this gene
between strains C91 and D23. In embodiments, the N. eutropha
described herein comprise a gene at least about 99.0%, 99.2%,
99.4%, 99.6%, 99.8%, or 100% identical to the D23 hao1 gene.
[0317] The hao2 genes are about 99.4% identical (i.e., at 1702/1713
positions). Accordingly, in some embodiments, the N. eutropha
described herein comprise D23 nucleotides at at least 1, 2, 3, 4,
5, 6, 7, 8, 9, 10, 11, or all of the positions that differ in this
gene between strains C91 and D23. In embodiments, the N. eutropha
described herein comprise D23 nucleotides at at most 1, 2, 3, 4, 5,
6, 7, 8, 9, 10, 11, or all of the positions that differ in this
gene between strains C91 and D23. In embodiments, the N. eutropha
described herein comprise a gene at least about 99.4%, 99.6%,
99.8%, or 100% identical to the D23 hao2 gene.
[0318] The hao3 genes are about 99.2% identical (i.e., at 1700/1713
positions). Accordingly, in some embodiments, the N. eutropha
described herein comprise D23 nucleotides at at least 1, 2, 3, 4,
5, 6, 7, 8, 9, 10, 11, 12, 13, or all of the positions that differ
in this gene between strains C91 and D23. In embodiments, the N.
eutropha described herein comprise D23 nucleotides at at most 1, 2,
3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, or all of the positions that
differ in this gene between strains C91 and D23. In embodiments,
the N. eutropha described herein comprise a gene at least about
99.2%, 99.4%, 99.6%, 99.8%, or 100% identical to the D23 hao3
gene.
[0319] The cycA1 genes are about 98.0% identical (i.e., at 694/708
positions). Accordingly, in some embodiments, the N. eutropha
described herein comprise D23 nucleotides at at least 1, 2, 3, 4,
5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or all of the positions that
differ in this gene between strains C91 and D23. In embodiments,
the N. eutropha described herein comprise D23 nucleotides at at
most 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or all of the
positions that differ in this gene between strains C91 and D23. In
embodiments, the N. eutropha described herein comprise a gene at
least about 98.0%, 98.2%, 98.4%, 98.6%, 98.8%, 99.0%, 99.2%, 99.4%,
99.6%, 99.8%, or 100% identical to the D23 cycA1 gene.
[0320] The cycA2 genes are about 98.7% identical (i.e., at 699/708
positions). Accordingly, in some embodiments, the N. eutropha
described herein comprise D23 nucleotides at at least 1, 2, 3, 4,
5, 6, 7, 8, 9, 10, 11, or all of the positions that differ in this
gene between strains C91 and D23. In embodiments, the N. eutropha
described herein comprise D23 nucleotides at at most 1, 2, 3, 4, 5,
6, 7, 8, 9, 10, 11, or all of the positions that differ in this
gene between strains C91 and D23. In embodiments, the N. eutropha
described herein comprise a gene at least about 98.7%, 98.8%,
99.0%, 99.2%, 99.4%, 99.6%, 99.8%, or 100% identical to the D23
cycA2 gene.
[0321] The cycA3 genes are about 99.3% identical (i.e., at 703/708
positions). Accordingly, in some embodiments, the N. eutropha
described herein comprise D23 nucleotides at at least 1, 2, 3, 4,
5, or all of the positions that differ in this gene between strains
C91 and D23. In embodiments, the N. eutropha described herein
comprise D23 nucleotides at at most 1, 2, 3, 4, 5, or all of the
positions that differ in this gene between strains C91 and D23. In
embodiments, the N. eutropha described herein comprise a gene at
least about 99.3%, 99.4%, 99.6%, 99.8%, or 100% identical to the
D23 cycA3 gene.
[0322] The cycB1 genes are about 96.7% identical (i.e., at 696/720
positions). Accordingly, in some embodiments, the N. eutropha
described herein comprise D23 nucleotides at at least 1, 2, 3, 4,
5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22,
23, 24, 25, 26, or all of the positions that differ in this gene
between strains C91 and D23. In embodiments, the N. eutropha
described herein comprise D23 nucleotides at at most 1, 2, 3, 4, 5,
6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23,
24, 25, 26, or all of the positions that differ in this gene
between strains C91 and D23. In embodiments, the N. eutropha
described herein comprise a gene at least about 96.7%, 96.8%,
97.0%, 97.2%, 97.4%, 97.6%, 97.8%, 98.0%, 98.2%, 98.4%, 98.4%,
98.6%, 98.8%, 99.0%, 99.2%, 99.4%, 99.6%, 99.8%, or 100% identical
to the D23 cycB1 gene.
[0323] The cycB2 genes are about 97.1% identical (i.e., at 702/723
positions). Accordingly, in some embodiments, the N. eutropha
described herein comprise D23 nucleotides at at least 1, 2, 3, 4,
5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, or
all of the positions that differ in this gene between strains C91
and D23. In embodiments, the N. eutropha described herein comprise
D23 nucleotides at at most 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,
13, 14, 15, 16, 17, 18, 19, 20, 21, or all of the positions that
differ in this gene between strains C91 and D23. In embodiments,
the N. eutropha described herein comprise a gene at least about
97.1%, 97.2%, 97.4%, 97.6%, 97.8%, 98.0%, 98.2%, 98.4%, 98.4%,
98.6%, 98.8%, 99.0%, 99.2%, 99.4%, 99.6%, 99.8%, or 100% identical
to the D23 cycB2 gene.
[0324] The following four paragraphs describe genes and proteins of
Table 1 in more detail.
[0325] Ammonia monooxygenase is an enzyme involved in ammonia
oxidation, that catalyzes the reaction
NH.sub.3+O.sub.2+2e.sup.-+2H.sup.+ NH.sub.2OH+H.sub.2O (Ensign et
al., 1993). In N. eutropha strain D23, the ammonia monooxygenase
operon comprises three genes designated amoA, amoB, and amoC.
Strain D23 comprises two copies of the entire operon, and a third
copy of amoC. These genes and the corresponding proteins are listed
in Table 1 above. In certain embodiments, the N. eutropha described
herein comprise 1 or 2 ammonia monooxygenase subunit A genes and/or
protein of Table 1 (e.g., the D23 sequences of Table 1), or genes
and/or proteins similar thereto. In some embodiments, the N.
eutropha described herein comprise 1 or 2 ammonia monooxygenase
subunit B genes and/or proteins of Table 1 (e.g., the D23 sequences
of Table 1), or genes and/or proteins similar thereto. In certain
embodiments, the N. eutropha described herein comprise 1, 2, or 3
ammonia monooxygenase subunit C genes and/or proteins of Table 1
(e.g., the D23 sequences of Table 1), or genes and/or proteins
similar thereto. In some embodiments, the N. eutropha described
herein comprise at least one or two each of (a) an ammonia
monooxygenase subunit A gene and/or protein of Table 1 (e.g., the
D23 sequences of Table 1), (b) an ammonia monooxygenase subunit B
gene and/or protein of Table 1 (e.g., the D23 sequences of Table
1), and (c) an ammonia monooxygenase subunit C gene and/or protein
of Table 1 (e.g., the D23 sequences of Table 1). For instance, the
N. eutropha may comprise all of the ammonia monooxygenase genes
and/or proteins of Table 1 (e.g., the D23 sequences of Table 1), or
genes and/or proteins similar thereto. Even more specifically, in
some embodiments, the N. eutropha comprises all of the D23 ammonia
monooxygenase genes of Table 1. In some embodiments, the N.
eutropha comprises all of the D23 ammonia monooxygenase proteins of
Table 1. Hydroxylamine oxidoreductases catalyze the general
reaction NH.sub.2OH+O.sub.2 NO.sub.2.sup.-+H.sub.2O. They typically
use heme as a cofactor. N. eutropha strain D23 comprises three
hydroxylamine oxidoreductases, designated hao1, hao2, and hao3.
These genes and the corresponding proteins are listed in Table 1
above. In some embodiments, the N. eutropha described herein
comprise 1, 2, or 3 hydroxylamine oxidoreductase genes and/or
proteins of Table 1 (e.g., the D23 sequences of Table 1), or genes
and/or proteins similar thereto. For instance, the N. eutropha may
comprise all of the hydroxylamine oxidoreductase genes and/or
proteins of Table 1 (e.g., the D23 sequences of Table 1), or genes
and/or proteins similar thereto. Even more specifically, in some
embodiments, the N. eutropha comprises all of the D23 hydroxylamine
oxidoreductase genes of Table 1. In some embodiments, the N.
eutropha comprises all of the D23 hydroxylamine oxidoreductase
proteins of Table 1.
[0326] The capacity of D23 to aerobically catabolize ammonia as the
sole source of energy and reductant requires two specialized
protein complexes, Amo and Hao as well as the cytochromes c554 and
c.sub.m552, which relay the electrons to the quinone pool. The NO
reductase activity of c554 is important during ammonia oxidation at
low oxygen concentrations. N. eutropha strain D23 comprises three
cytochrome c554 genes, designated cycA1, cycA2, and cycA3. These
genes and the corresponding proteins are listed in Table 1 above.
In some embodiments, the N. eutropha described herein comprise 1,
2, or 3 cytochrome c554 genes and/or proteins of Table 1 (e.g., the
D23 sequences of Table 1), or genes and/or proteins similar
thereto. For instance, the N. eutropha may comprise all of the
cytochrome c554 genes and/or proteins of Table 1 (e.g., the D23
sequences of Table 1), or genes and/or proteins similar thereto.
Even more specifically, in some embodiments, the N. eutropha
comprises all of the D23 cytochrome c554 genes of Table 1. In some
embodiments, the N. eutropha comprises all of the D23 cytochrome
c554 proteins of Table 1.
[0327] The capacity of D23 to aerobically catabolize ammonia as the
sole source of energy and reductant requires two specialized
protein complexes, Amo and Hao as well as the Cytochromes c554 and
c.sub.M552, which relay the electrons to the quinone pool.
Cytochrome c.sub.M552 reduces quinones, with electrons originating
from Hao. N. eutropha strain D23 comprises two cytochrome
c.sub.M552 genes, designated cycB1 and cycB2. These genes and the
corresponding proteins are listed in Table 1 above. In some
embodiments, the N. eutropha described herein comprise 1 or 2
cytochrome c.sub.M552 genes and/or proteins of Table 1 (e.g., the
D23 sequences of Table 1), or genes and/or proteins similar
thereto. For instance, the N. eutropha may comprise both of the
cytochrome c.sub.M552 genes and/or proteins of Table 1 (e.g., the
D23 sequences of Table 1), or genes and/or proteins similar
thereto. Even more specifically, in some embodiments, the N.
eutropha comprises both of the D23 cytochrome c.sub.M552 genes of
Table 1. In some embodiments, the N. eutropha comprises both of the
D23 Cytochrome c.sub.M552 proteins of Table 1.
[0328] In some embodiments, the N. eutropha described herein
comprises a combination of genes and/or proteins selected from
Table 1. This combination may comprise, for instance, genes and/or
proteins listed in the preceding four paragraphs. For instance, the
combination may comprise genes and/or proteins from two classes
within Table 1. Accordingly, in some embodiments, the N. eutropha
comprises one or more ammonia monooxygenase genes and/or proteins
and one or more hydroxylamine oxidoreductase genes and/or proteins
as described in Table 1, or as described in the preceding four
paragraphs. In embodiments, the N. eutropha comprises one or more
ammonia monooxygenase genes and/or proteins and one or more
cytochrome c554 genes and/or proteins as described in Table 1, or
as described in the preceding four paragraphs. In embodiments, the
N. eutropha comprises one or more ammonia monooxygenase genes
and/or proteins and one or more cytochrome c.sub.M552 genes and/or
proteins as described in Table 1, or as described in the preceding
four paragraphs. In embodiments, the N. eutropha comprises one or
more hydroxylamine oxidoreductase genes and/or proteins and one or
more cytochrome c554 genes and/or proteins as described in Table 1,
or as described in the preceding four paragraphs. In embodiments,
the N. eutropha comprises one or more hydroxylamine oxidoreductase
genes and/or proteins and one or more cytochrome c.sub.M552 genes
and/or proteins as described in Table 1, or as described in the
preceding four paragraphs.
[0329] The combination may also comprise genes and/or proteins from
three classes within Table 1. Accordingly, in some embodiments, the
N. eutropha comprises one or more ammonia monooxygenase genes
and/or proteins and one or more hydroxylamine oxidoreductase genes
and/or proteins and one or more cytochrome c554 genes and/or
proteins as described in Table 1, or as described in the
aforementioned four paragraphs. In embodiments, the N. eutropha
comprises one or more ammonia monooxygenase genes and/or proteins
and one or more hydroxylamine oxidoreductase genes and/or proteins
and one or more cytochrome c.sub.M552 genes and/or proteins as
described in Table 1, or as described in the aforementioned four
paragraphs. In embodiments, the N. eutropha comprises one or more
one or more ammonia monooxygenase genes and/or proteins and one or
more cytochrome c554 genes and/or proteins and/or one or more
cytochrome c.sub.M552 genes and/or proteins as described in Table
1, or as described in the aforementioned four paragraphs. In
embodiments, the N. eutropha comprises one or more one or more
hydroxylamine oxidoreductase genes and/or proteins and one or more
cytochrome c554 genes and/or proteins and/or one or more cytochrome
c.sub.M552 genes and/or proteins as described in Table 1, or as
described in the aforementioned four paragraphs.
[0330] The combination may comprise genes and/or proteins from all
four classes within Table 1. Accordingly, in some embodiments, the
N. eutropha comprises one or more ammonia monooxygenase genes
and/or proteins and one or more hydroxylamine oxidoreductase genes
and/or proteins and one or more cytochrome c554 genes and/or
proteins and/or one or more cytochrome c.sub.M552 genes as
described in Table 1, or as described in the aforementioned four
paragraphs.
[0331] Table 2 (below) lists sequence differences between the D23
and C91 proteins of Table 1. For example, AmoA1 has M at position 1
in C91 but V at position 1 in D23, and this difference is
abbreviated as M1V in Table 2. As another example, the D23 CycB1
has an insertion of DDD between residues 194 and 195 of the C91
protein, so that the added residues are residues number 195, 196,
and 197 of the D23 protein and this difference is abbreviated as
195insD, 196insD, and 197insD respectively in Table 2. The sequence
alignments that form the basis for Table 2 are shown in FIGS.
10-16.
TABLE-US-00002 TABLE 2 Amino acid sequence differences between N.
eutropha strains D23 and C91 Protein Sequence characteristics of
D23 compared to C91 1. ammonia monooxygenase AmoA1 M1V, M160L,
P167A AmoA2 M1V, M160L, P167A AmoB1 I33V, V165I AmoB2 I33V, V165I
AmoC1 N/A AmoC2 N/A AmoC3 V79A, I271V 2. hydroxylamine
oxidoreductase Hao1 N85S, V163A, G312E Hao2 N85S, G312E Hao3 N85S,
G312E 3. cytochrome c554 c554 CycA1 A65T, A186T c554 CycA2 A65T
c554 CycA3 A65T 4. cytochrome c.sub.M552 c.sub.M552 CycB1 I63V,
S189P, D194G, 195insD, 196insD, 197insD, 206insE, 207insE
c.sub.M552 CycB2 I63V, S189P, 206insE, 207insE
[0332] Accordingly, the N. eutropha described herein may comprise
one or more of the sequence characteristics listed in Table 2. For
instance, the N. eutropha may comprise at least 1, 2, 3, 4, 5, 10,
15, 20, 25, 30, or all of the sequence characteristics of Table 2.
In some embodiments, the N. eutropha comprises no more than 2, 3,
4, 5, 10, 15, 20, 25, 30, or all of the sequence characteristics of
Table 2. In embodiments, the N. eutropha comprises 1-5, 5-10,
10-15, 15-20, 20-25, 25-30, or all of the sequence characteristics
of Table 2. The N. eutropha may also comprise fragments of said
proteins.
[0333] As to individual categories of genes or proteins, in some
embodiments, the N. eutropha comprises at least 1, 2, 3, 4, 5, 6,
7, 8, 9, 10, or all of the sequence characteristics of Table 2,
Section 1 (which describes ammonia monooxygenases). In embodiments,
the N. eutropha comprises 1-5, 3-7, 4-8, or 5-10 of the sequence
characteristics of Table 2, Section 1. For instance, in some
embodiments, the N. eutropha comprises at least 1, 2, or 3 sequence
characteristics of an amoA gene or protein as listed in Table 2,
and/or no more than 2 or 3 of these characteristics. The N.
eutropha may also comprise at least 1 or 2 sequence characteristics
of an amoB gene or protein as listed in Table 2. In addition, the
N. eutropha may comprise at least 1 or 2 sequence characteristics
of the amoC3 gene as listed in Table 2. The N. eutropha may also
comprise fragments of said proteins.
[0334] With respect to hao genes and proteins, the N. eutropha may
comprise at least 1, 2, 3, 4, 5, 6, 7, 8, or all of the sequence
characteristics of Table 2, Section 2 (which describes
hydroxylamine oxidoreductases). In embodiments, the N. eutropha
comprises 1-4, 2-5, 3-6, or 4-8 of the sequence characteristics of
Table 2, Section 2. The N. eutropha may also comprise at least 1, 2
or 3 sequence characteristics of Hao1 as listed in Table 1, and/or
no more than 2 or 3 of these characteristics. The N. eutropha may
also comprise at least 1 or 2 sequence characteristics of Hao2 or
Hao3 as listed in Table 2. The N. eutropha may also comprise
fragments of said proteins.
[0335] Turning now to cytochrome c554, the N. eutropha may comprise
at least 1, 2, 3, 4, or all of the sequence characteristics of
Table 2, Section 3 (which describes cytochrome c554). In
embodiments, the N. eutropha comprises at most 2, 3, 4, or all of
the sequence characteristics of Table 2 Section 3. In embodiments,
the N. eutropha comprises at least 1 or 2 sequence characteristics
of cytochrome c554 CycA1 as listed in Table 2. The N. eutropha may
also comprise at least 1 sequence characteristic of c554 CycA2 or
c554 CycA3 as listed in Table 2. The N. eutropha may also comprise
fragments of said proteins.
[0336] With respect to the c.sub.M552 genes and proteins, the N.
eutropha may comprise at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or
all of the sequence characteristics of Table 2, Section 4 (which
describes cytochrome c.sub.M552). In embodiments, the N. eutropha
comprises at most 2, 3, 4, 5, 6, 7, 8, 9, 10, or all the sequence
characteristics of Table 2, Section 4. For instance, in embodiments
the N. eutropha comprises 1-5, 2-7, 3-8, or 5-10 sequence
characteristics of Table 2, Section 4. In embodiments, at least 1,
2, 3, 4, 5, 6, or 7 sequence characteristics of c.sub.M552 CycB1 as
listed in Table 2, and/or no more than 2, 3, 4, 5, 6, or 7 of these
characteristics. The N. eutropha may also comprise at least 1, 2,
or 3 sequence characteristics of c.sub.M552 CycB2 as listed in
Table 2, and/or no more than 2 or 3 of these characteristics. The
N. eutropha may also comprise fragments of said proteins.
[0337] It is understood that the paragraphs above, which refer to
sequence characteristics of various N. eutropha proteins, also
describe the sequences of nucleic acids that encode these
proteins.
[0338] The sequencing analysis described herein revealed that
strain D23 lacks plasmids. Consequently, in some embodiments, the
N. eutropha bacterium lacks plasmids, i.e., all of its DNA is
contained in the chromosome. In some embodiments, the N. eutropha
bacterium lacks endogenous plasmids, but carries one or more
transgenic plasmids.
[0339] This D23 strain is not believed to be a product of nature,
but rather has acquired certain mutations and characteristics
during an extended period of culture and selection in the
laboratory. For instance, D23 has an ability to grow in conditions
of greater than about 200 or 250 mM NH.sub.4.sup.+ for more than 24
hours.
[0340] In some embodiments, the N. eutropha disclosed herein differ
from naturally occurring bacteria in the abundance of siderophores.
For instance, the N. eutropha may have elevated or reduced levels
of siderophores compared to N. eutropha C91. Generally,
siderophores are secreted iron-chelating compounds that help
bacteria scavenge iron from their environment. Some siderophores
are peptides, and others are small organic molecules.
[0341] The AOBs, for example, N. eutropha contemplated in this
disclosure may comprise mutations relative to wild-type N. eutropha
and/or the N. eutropha sequences disclosed herein. These mutations
may, e.g., occur spontaneously, be introduced by random
mutagenesis, or be introduced by targeted mutagenesis. For
instance, the N. eutropha may lack one or more genes or regulatory
DNA sequences that wild-type N. eutropha typically comprises. The
N. eutropha may also comprise point mutations, substitutions,
insertions, deletions, and/or rearrangements relative to the
sequenced strain or a wild-type strain. The N. eutropha may be a
purified preparation of optimized N. eutropha.
[0342] In certain embodiments, the N. eutropha is transgenic. For
instance, it may comprise one or more genes or regulatory DNA
sequences that wild-type N. eutropha D23 lacks. More particularly,
the N. eutropha may comprise, for instance, a reporter gene, a
selective marker, a gene encoding an enzyme, or a promoter
(including an inducible or repressible promoter). In some
embodiments the additional gene or regulatory DNA sequence is
integrated into the bacterial chromosome; in some embodiments the
additional gene or regulatory DNA sequence is situated on a
plasmid, for instance a plasmid related to a plasmid found in N.
eutropha N91.
[0343] In some preferred embodiments, the N. eutropha differs by at
least one nucleotide from naturally occurring bacteria. For
instance, the N. eutropha may differ from naturally occurring
bacteria in a gene or protein that is part of a relevant pathway,
e.g., an ammonia metabolism pathway, a urea metabolism pathway, or
a pathway for producing nitric oxide or nitric oxide precursors.
More particularly, the N. eutropha may comprise a mutation that
elevates activity of the pathway, e.g., by increasing levels or
activity of an element of that pathway.
[0344] The above-mentioned mutations can be introduced using any
suitable technique. Numerous methods are known for introducing
mutations into a given position. For instance, one could use
site-directed mutagenesis, oligonucleotide-directed mutagenesis, or
site-specific mutagenesis. Non-limiting examples of specific
mutagenesis protocols are described in, e.g., Mutagenesis, pp.
13.1-13.105 (Sambrook and Russell, eds., Molecular Cloning A
Laboratory Manual, Vol. 3, 3.sup.rd ed. 2001). In addition,
non-limiting examples of well-characterized mutagenesis protocols
available from commercial vendors include, without limitation,
Altered Sites.RTM. II in vitro Mutagenesis Systems (Promega Corp.,
Madison, Wis.); Erase-a-Base.RTM. System (Promega, Madison, Wis.);
GeneTailor.TM. Site-Directed Mutagenesis System (Invitrogen, Inc.,
Carlsbad, Calif.); QuikChange.RTM. II Site-Directed Mutagenesis
Kits (Stratagene, La Jolla, Calif.); and Transformer.TM.
Site-Directed Mutagenesis Kit (BD-Clontech, Mountain View,
Calif.).
[0345] In some embodiments, the preparation of ammonia oxidizing
bacteria may comprise a concentration or amount of ammonia
oxidizing bacteria in order to at least partially treat a condition
or disease. The preparation of ammonia oxidizing bacteria may
comprise a concentration or amount of ammonia oxidizing bacteria in
order to alter, e.g., reduce or increase, an amount, concentration
or proportion of a bacterium, or genus of bacteria, on a surface,
e.g., a skin surface. The bacteria may be non-pathogenic or
pathogenic, or potentially pathogenic.
[0346] In some embodiments, the preparation of ammonia oxidizing
bacteria may comprise between about 10.sup.8 to about 10.sup.14
CFU/L. The preparation may comprise at least 10.sup.8, 10.sup.9,
10.sup.10, 10.sup.11, 2.times.10.sup.11, 5.times.10.sup.11,
10.sup.12, 2.times.10.sup.12, 5.times.10.sup.12, 10.sup.13,
2.times.10.sup.13, 5.times.10.sup.13, or 10.sup.14; or about
10.sup.8-10.sup.9, 10.sup.9-10.sup.10, 10.sup.11-10.sup.11,
10.sup.11-10.sup.12, 10.sup.12-10.sup.13, or 10.sup.13-10.sup.14
CFU/L. In certain aspects, the preparation may comprise between
about 1.times.10.sup.9 CFU/L to about 10.times.10.sup.9 CFU/L. In
certain aspects, the preparation may comprise between about
1.times.10.sup.9 CFU to about 10.times.10.sup.9 CFU.
[0347] In some embodiments, the preparation of ammonia oxidizing
bacteria may comprise between about 0.1 milligrams (mg) and about
1000 mg of ammonia oxidizing bacteria. In certain aspects, the
preparation may comprise between about 50 mg and about 1000 mg of
ammonia oxidizing bacteria. The preparation may comprise between
about 0.1-0.5 mg, 0.2-0.7 mg, 0.5-1.0 mg, 0.5-2 mg, 0.5-5 mg, 2.5-5
mg, 2.5-7.0 mg, 5.0-10 mg, 7.5-15 mg, 10-15 mg, 15-20 mg, 15-25 mg,
20-30 mg, 25-50 mg, 25-75 mg, 50-75 mg, 50-100 mg, 75-100 mg,
100-200 mg, 200-300 mg, 300-400 mg, 400-500 mg, 500-600 mg, 600-700
mg, 700-800 mg, 800-900 mg, 900-1000 mg, 100-250 mg, 250-500 mg,
100-500 mg, 500-750 mg, 750-1000 mg, or 500-1000 mg.
[0348] In some embodiments, the preparation of ammonia oxidizing
bacteria may comprise a mass ratio of ammonia oxidizing bacteria to
an excipient, e.g., a pharmaceutically acceptable excipient or a
cosmetically acceptable excipient in a range of about 0.1 grams per
liter to about 1 gram per liter. The preparation may comprise a
mass ratio of ammonia oxidizing bacteria to an excipient in a range
of about 0.1-0.2, 0.2-0.3, 0.1-0.5, 0.2-0.7, 0.5-1.0, or 0.7-1.0
grams per liter.
[0349] In some embodiments, the preparation of ammonia oxidizing
bacteria may be in a growth state. A growth state may be provided
by exposing ammonia oxidizing bacteria to an environment that may
promote growth. The growth state may be a state, e.g., ammonia
oxidizing bacteria in an environment that allows immediate
availability of ammonia oxidizing bacteria to convert ammonium ions
(NH.sub.4.sup.+) to nitrite (NO.sub.2.sup.-). The growth state may
comprise providing ammonia oxidizing bacteria in an environment
having a pH of greater than about 7.6. The growth state may also
comprise providing ammonia oxidizing bacteria in an environment
having ammonia, ammonium salts, and/or urea, trace minerals and
sufficient oxygen and carbon dioxide, as described above in Section
1.
[0350] In some embodiments, the preparation of ammonia oxidizing
bacteria may be in a polyphosphate loading state, wherein the state
or the environment, e.g., a media, e.g., a culture media, e.g., a
growth media, may have a pH of less than about 7.4. Levels of at
least one of ammonia, ammonium ions, and urea may be between about
10 micromolar and 200 millimolar. Levels of trace materials may be
between 0.1 micromolar iron and 20 micromolar iron. Levels of
oxygen may be between about 5% and 100% oxygen saturation. Levels
of carbon dioxide may be between/less than about zero and 200 ppm,
and phosphate levels greater than about 10 micromolar. The purpose
of the polyphosphate loading state is to provide AOB with ammonia
and oxygen such that ATP can be produced, but to deny them carbon
dioxide and carbonate such that they are unable to use that ATP to
fix carbon dioxide and instead use that ATP to generate
polyphosphate which may be stored.
[0351] In some embodiments, the preparation of ammonia oxidizing
bacteria may be in a storage state. A storage state may be defined
as ammonia oxidizing bacteria in an environment in which they may
be stored to be later revived. The storage state may be a state,
e.g., ammonia oxidizing bacteria in an environment that allows
availability of ammonia oxidizing bacteria after being revived,
e.g., after being place in an environment promoting a growth state
for a pre-determined period of time.
[0352] The storage state may comprise providing ammonia oxidizing
bacteria in an environment having a pH of less than about 7.4. The
storage state may also comprise providing ammonia oxidizing
bacteria in an environment having ammonia, ammonia salts, and/or
urea, trace minerals, oxygen, and low concentrations of carbon
dioxide, as described above in Section 1.
[0353] Storage may also be accomplished by storing at 4.degree. C.
for up to several months. The storage buffer in some embodiments
may comprise 50 mM Na.sub.2HPO.sub.4-2 mM MgCl.sub.2 (pH 7.6).
[0354] In some embodiments, ammonia oxidizing bacteria may be
cyropreserved. A 1.25 ml of ammonia oxidizing bacteria mid-log
culture may be added to a 2 ml cryotube and 0.75 ml of sterile 80%
glycerol. Tubes may be shaken gently, and incubate at room
temperature for 15 min to enable uptake of the cryoprotective
agents by the cells. The tubes may be directly stored in a
-80.degree. C. freezer for freezing and storage.
[0355] For resuscitation of cultures, frozen stocks may be thawed
on ice for 10-20 minutes, and then centrifuged at 8,000.times.g for
3 minutes at 4.degree. C. The pellet may be washed by suspending it
in 2 ml AOB medium followed by another centrifugation at
8,000.times.g for 3 minutes at 4.degree. C. to reduce potential
toxicity of the cryoprotective agents. The pellet may be
resuspended in 2 ml of AOB medium, inoculated into 50 ml of AOB
medium containing 50 mM NH.sub.4.sup.+, and incubated in dark at
30.degree. C. by shaking at 200 rpm.
[0356] In some embodiments, the preparation of ammonia oxidizing
bacteria may comprise ammonia oxidizing bacteria in a storage state
and/or ammonia oxidizing bacteria in a polyphosphate loading state
and/or ammonia oxidizing bacteria in a growth state.
[0357] Without wishing to be bound by theory, by maintaining
ammonia oxidizing bacteria under conditions or in an environment of
low carbon dioxide, with sufficient oxygen and ammonia, they may
accumulate polyphosphate for a pre-determined period, e.g., for a
period of about one doubling time, e.g., for about 8-12 hours,
e.g., for about 10 hours. The ammonia oxidizing bacteria may
accumulate sufficient polyphosphate to extend their storage
viability, storage time, and accelerate their revival. This may
occur with or without the addition of buffer and ammonia.
[0358] The presence of sufficient stored polyphosphate may allow
the ammonia oxidizing bacteria the ATP resources to maintain
metabolic activity even in the absence of ammonia and oxygen, and
to survive insults that would otherwise be fatal.
[0359] The process of oxidation of ammonia to generate ATP has two
steps. The first step is the oxidation of ammonia to hydroxylamine
by ammonia monoxoygenase (Amo), followed by the conversion of
hydroxylamine to nitrite by hydroxylamine oxidoreductase (Hao).
Electrons from the second step (conversion of hydroxylamine to
nitrite) are used to power the first step (oxidation of ammonia to
hydroxylamine).
[0360] If an ammonia oxidizing bacteria does not have hydroxylamine
to generate electrons for Amo, then hydroxylamine is not available
for Hao. For example, acetylene irreversibly inhibits the enzyme
crucial for the first step in the oxidation of ammonia to nitrite,
the oxidation of ammonia to hydroxylamine. Once AOB are exposed to
acetylene, Amo is irreversibly inhibited and new enzyme must be
synthesized before hydroxylamine can be generated. In a normal
consortium biofilm habitat, AOB may share and receive hydroxylamine
form other AOB (even different strains with different
susceptibilities to inhibitors) and so the biofilm tends to be more
resistant to inhibitors such as acetylene than an individual
organism. AOB can use stored polyphosphate to synthesize new Amo,
even in the absence of hydroxylamine.
[0361] Any embodiment, preparation, composition, or formulation of
ammonia oxidizing bacteria discussed herein may comprise, consist
essentially of, or consist of optionally axenic ammonia oxidizing
bacteria.
3. METHODS OF PRODUCING N. EUTROPHA
[0362] Methods of culturing various Nitrosomonas species are known
in the art. N. eutropha may be cultured, for example, using N.
europaea medium as described in Example 2 below. Ammonia oxidizing
bacteria may be cultured, for example, using the media described in
Table 3 or Table 4, above.
[0363] N. eutropha may be grown, for example, in a liquid culture
or on plates. Suitable plates include 1.2% R2A agar, 1.2% agar,
1.2% agarose, and 1.2% agarose with 0.3 g/L pyruvate.
[0364] In some embodiments, ammonia oxidizing bacteria, such as N.
eutropha is cultured in organic free media. One advantage of using
organic free media is that it lacks substrate for heterotrophic
bacteria to metabolize except for that produced by the autotrophic
bacteria. Another advantage of using the as-grown culture is that
substantial nitrite accumulates in the culture media, and this
nitrite is also inhibitory of heterotrophic bacteria and so acts as
a preservative during storage.
[0365] In some embodiments, ammonia oxidizing bacteria such as an
N. eutropha strain with improved, e.g. optimized, properties is
produced by an iterative process of propagation and selecting for
desired properties. In some embodiments, the selection and
propagation are carried out simultaneously. In some embodiments,
the selection is carried out in a reaction medium (e.g., complete
N. europaea medium) comprising 50 mM, 75 mM, 100 mM, 125 mM, 150
mM, 175 mM, 200 mM, 225 mM, 250 mM, 275 mM, or 300 mM
NH.sub.4.sup.+, e.g., at least 200 mM NH.sub.4.sup.+. In some
embodiments, the period of propagation and/or selection is at least
1, 2, 3, or 6 months. In embodiments, the period of propagation
and/or selection is at least 1, 2, 4, 6, 8, or 10 years.
[0366] In some aspects, the ammonia oxidizing bacteria, such as the
N. eutropha are manufactured on a commercial scale. In some
embodiments, commercial scale refers to a liquid culturing method
with a culture medium volume of at least 10,000, 20,000, 30,000,
50,000, or 100,000 liters (L). In some embodiments, the bacteria
are produced in a bioreactor. The bioreactor may maintain the
bacteria at a constant temperature, e.g., about 26-30 degrees
Celsius using, for example a thermal jacket for insulation, a
temperature sensor, and a heating or cooling element. The
bioreactor may have an apparatus for stirring the culture to
improve distribution of nutrients like ammonia, urea, oxygen,
carbon dioxide, and various minerals. The bioreactor may also have
an inlet tube for addition of new medium, and an outlet tube for
collection of cells. The bioreactor may also have an aerator for
distributing oxygen and/or carbon dioxide to the culture. The
bioreactor may be, e.g., a batch reactor, a fed batch reactor, or a
continuous reactor. In some embodiments, commercial scale
production of N. eutropha yields a batch of 1,000 to 100,000 L per
day at about 10.sup.12 CFU/liter and 1,000 to 100,000. The
commercial scale production may yield e.g., a batch of 1,000-5,000,
5,000-10,000, 10,000-50,000, or 50,000-100,000 L/day. The
commercial scale production may yield e.g., a batch of 1,000-5,000,
5,000-10,000, 10,000-50,000, or 50,000-100,000 L per batch. In some
embodiments, the yield is at a concentration of at least 10.sup.10,
10.sup.11, 2.times.10.sup.11, 5.times.10.sup.11, or 10.sup.12, or
about 10.sup.10-10.sup.11, 10.sup.11-10.sup.12,
10.sup.12-10.sup.13, or 10.sup.13-10.sup.14 CFU/L
[0367] In some embodiments, typically including commercial scale
production, quality control (QC) testing steps are carried out. The
general steps of QC typically comprise, 1) culturing N. eutropha,
2) performing a testing step on the culture or an aliquot thereof,
and 3) obtaining a value from the testing step, and optionally: 4)
comparing the obtained value to a reference value or range of
acceptable values, and 5) if the obtained value meets the
acceptable reference value or range, then classifying the culture
as acceptable, and if the obtained value does not meet the
acceptable reference value or range, then classifying the culture
as unacceptable. If the culture is classified as acceptable, the
culture may, e.g., be allowed to continue growing and/or may be
harvested and added to a commercial product. If the culture is
classified as unacceptable, the culture may, e.g., be safely
disposed of or the defect may be remedied.
[0368] The testing step may comprise measuring the optical density
(OD) of the culture. OD is measured in a spectrophotometer, and
provides information on the amount of light transmitted through the
sample as distinguished from light absorbed or scattered. In some
embodiments, the OD600 (e.g., optical density of light with a
wavelength of 600 nm) may be determined. This measurement typically
indicates the concentration of cells in the medium, where a higher
optical density corresponds to a higher cell density.
[0369] The testing step may comprise measuring the pH of the
culture. The pH of an N. eutropha culture indicates the rate of
nitrogen oxidation, and can also indicate whether the culture
comprises a contaminating organism. pH may be measured using, e.g.,
a pH-sensing device comprising a electrode (such as a hydrogen
electrode, quinhydron-Electrode, antimony electrode, glass
electrode), a pH-sensing device comprising a semiconductor, or a
color indicator reagent such as pH paper.
[0370] In certain embodiments, producing the ammonia oxidizing
bacteria such as N. eutropha comprises carrying out various quality
control steps. For instance, one may test the medium in which the
N. eutropha is grown, e.g., to determine whether it has an
appropriate pH, whether it has a sufficiently low level of waste
products, and/or whether it has a sufficiently high level or
nutrients. One may also test for the presence of contaminating
organisms. A contaminating organism is typically an organism other
than an ammonia oxidizing bacteria such as N. eutropha, for
instance an organism selected Microbacterium sp., Alcaligenaceae
bacterium, Caulobacter sp., Burkodelia multivorans, Escherichia
coli, Klebsiella pneumoniae, and Staphylococcus aureus. One may
test for contaminants by, e.g., extracting DNA, amplifying it, and
sequencing a conserved gene such as 16S rRNA. One may also test for
contaminants by plating culture on agar plates and observing colony
morphology. N. eutropha typically forms red colonies, so non-red
colonies are often indicative of contaminating organisms.
4. COMPOSITIONS COMPRISING AMMONIA OXIDIZING BACTERIA; COMPOSITIONS
COMPRISING N. EUTROPHA
[0371] The present disclosure provides, inter alia, compositions
comprising ammonia oxidizing bacteria, e.g., a preparation of
ammonia oxidizing bacteria, or a purified preparation of ammonia
oxidizing bacteria e.g., a natural product, or a fortified natural
product. The compositions comprising ammonia oxidizing bacteria,
e.g., a preparation of ammonia oxidizing bacteria, or a purified
preparation of ammonia oxidizing bacteria may be provided in a
cosmetic product or a therapeutic product. The preparation may
comprise, inter alia, at least one of ammonia, ammonium salts, and
urea.
[0372] The present disclosure provides, inter alia, compositions
comprising N. eutropha, e.g., a purified preparation of an
optimized N. eutropha. In some embodiments, the N. eutropha in the
compositions has at least one property selected from an optimized
growth rate, an optimized NH.sub.4.sup.+ oxidation rate, and an
optimized resistance to NH.sub.4.sup.+.
[0373] In some aspects, the present disclosure provides
compositions with a defined number of species. For instance, this
disclosure provides a composition having N. eutropha and one other
type of organism, and no other types of organism. In other
examples, the composition has N. eutropha and 2, 3, 4, 5, 6, 7, 8,
9, or 10 other types of organism, and no other types of organism.
The other type of organism in this composition may be, for
instance, a bacterium, such as an ammonia-oxidizing bacterium.
Suitable ammonia-oxidizing bacteria for this purpose include those
in the genera Nitrosomonas, Nitrosococcus, Nitrosospira,
Nitrosocystis, Nitrosolobus, or Nitrosovibrio.
[0374] In some embodiments, the composition comprising N. eutropha
provides conditions that support N. eutropha viability. For
instance, the composition may promote N. eutropha growth and
metabolism or may promote a dormant state (e.g., freezing) from
which viable N. eutropha can be recovered. When the composition
promotes growth or metabolism, it may contain water and/or
nutrients that N. eutropha consumes, e.g., as ammonium, ammonia,
urea, oxygen, carbon dioxide, or trace minerals. In some
embodiments, the composition comprising ammonia oxidizing bacteria
provides conditions that support ammonia oxidizing bacteria
viability. For instance, the composition may promote ammonia
oxidizing bacteria growth and metabolism or may promote a dormant
state (e.g., freezing) or storage state as described herein, from
which viable ammonia oxidizing bacteria can be recovered. When the
composition promotes growth or metabolism, it may contain water
and/or nutrients that ammonia oxidizing bacteria consumes, e.g., as
ammonium ions, ammonia, urea, oxygen, carbon dioxide, or trace
minerals.
[0375] In some embodiments, one or more other organisms besides
ammonia oxidizing bacteria may be included in the preparation of
ammonia oxidizing bacteria. For example, an organism of the genus
selected from the group consisting of Lactobacillus, Streptococcus,
Bifidobacter, and combinations thereof, may be provided in the
preparation of ammonia oxidizing bacteria. In some embodiments, the
preparation may be substantially free of other organisms.
[0376] Preparations of ammonia oxidizing bacteria may comprise
between about between about 10.sup.8 to about 10.sup.14 CFU/L. The
preparation may comprise at least about 10.sup.8, 10.sup.9,
10.sup.10, 10.sup.11, 2.times.10.sup.11, 5.times.10.sup.11,
10.sup.12, 2.times.10.sup.12, 5.times.10.sup.12, 10.sup.13,
2.times.10.sup.13, 5.times.10.sup.13, or 10.sup.14; or about
10.sup.8-10.sup.9, 10.sup.9-10.sup.10, 10.sup.10-10.sup.11,
10.sup.11-10.sup.12, 10.sup.12-10.sup.13, or 10.sup.13-10.sup.14
CFU/L.
[0377] In some embodiments, the preparation may comprise at least
10.sup.8, 10.sup.9, 10.sup.10, 10.sup.11, 2.times.10.sup.11,
5.times.10.sup.11, 10.sup.12, 2.times.10.sup.12, 5.times.10.sup.12,
10.sup.13, 2.times.10.sup.13, 5.times.10.sup.13, or 10.sup.14; or
about 10.sup.8-10.sup.9, 10.sup.9-10.sup.10, 10.sup.10-10.sup.11,
10.sup.11-10.sup.12, 10.sup.12-10.sup.13, or 10.sup.13-10.sup.14
CFU/ml.
[0378] In some embodiments, the preparation may comprise between
about 1.times.10.sup.9 to about 10.times.10.sup.9 CFU/L. In some
embodiments, the preparation may comprise about 3.times.10.sup.10
CFU, e.g., 3.times.10.sup.10 CFU per day. In some embodiments, the
preparation may comprise about 1.times.10.sup.9 to about
10.times.10.sup.9 CFU, e.g., about 1.times.10.sup.9 to about
10.times.10.sup.9 CFU per day.
[0379] In some embodiments, the preparation of ammonia oxidizing
bacteria may comprise between about 0.1 milligrams (mg) and about
1000 mg of ammonia oxidizing bacteria. In certain aspects, the
preparation may comprise between about 50 mg and about 1000 mg of
ammonia oxidizing bacteria. The preparation may comprise between
about 0.1-0.5 mg, 0.2-0.7 mg, 0.5-1.0 mg, 0.5-2 mg, 0.5-5 mg, 2.5-5
mg, 2.5-7.0 mg, 5.0-10 mg, 7.5-15 mg, 10-15 mg, 15-20 mg, 15-25 mg,
20-30 mg, 25-50 mg, 25-75 mg, 50-75 mg, 50-100 mg, 75-100 mg,
100-200 mg, 200-300 mg, 300-400 mg, 400-500 mg, 500-600 mg, 600-700
mg, 700-800 mg, 800-900 mg, 900-1000 mg, 100-250 mg, 250-500 mg,
100-500 mg, 500-750 mg, 750-1000 mg, or 500-1000 mg.
[0380] In some embodiments, the preparation of ammonia oxidizing
bacteria my comprise a mass ratio of ammonia oxidizing bacteria to
an excipient, e.g., a pharmaceutically acceptable excipient or a
cosmetically acceptable excipient in a range of about 0.1 grams per
liter to about 1 gram per liter. The preparation may comprise a
mass ratio of ammonia oxidizing bacteria to an excipient in a range
of about 0.1-0.2, 0.2-0.3, 0.1-0.5, 0.2-0.7, 0.5-1.0, or 0.7-1.0
grams per liter.
[0381] Advantageously, a formulation may have a pH that promotes
AOB, e.g., N. eutropha viability, e.g., metabolic activity. Urea
would hydrolyze to ammonia and would raise the pH to 7 to 8. AOB
are very active at this pH range and would lower the pH to about 6
where the NH3 converts to ammonium and is unavailable. Lower pH
levels, e.g. about pH 4, are also acceptable. The ammonia oxidizing
bacteria, e.g., N. eutropha may be combined with one or more
pharmaceutically or cosmetically acceptable excipients. In some
embodiments, "pharmaceutically acceptable excipient" refers to a
pharmaceutically-acceptable material, composition, or vehicle, such
as a liquid or solid filler, diluent, solvent, or encapsulating
material. In some embodiments, each excipient is "pharmaceutically
acceptable" in the sense of being compatible with the other
ingredients of a pharmaceutical formulation, and suitable for use
in contact with the tissue or organ of humans and animals without
excessive toxicity, irritation, allergic response, immunogenicity,
or other problems or complications, commensurate with a reasonable
benefit/risk ratio. See, Remington: The Science and Practice of
Pharmacy, 21st ed.; Lippincott Williams & Wilkins:
Philadelphia, Pa., 2005; Handbook of Pharmaceutical Excipients, 6th
ed.; Rowe et al., Eds.; The Pharmaceutical Press and the American
Pharmaceutical Association: 2009; Handbook of Pharmaceutical
Additives, 3rd ed.; Ash and Ash Eds.; Gower Publishing Company:
2007; Pharmaceutical Preformulation and Formulation, 2nd ed.;
Gibson Ed.; CRC Press LLC: Boca Raton, Fla., 2009.
[0382] In some embodiments, a cosmetically acceptable excipient
refers to a cosmetically acceptable material, composition, or
vehicle, such as a liquid or solid filler, diluent, solvent, or
encapsulating material. In some embodiments, each excipient is
cosmetically acceptable in the sense of being compatible with the
other ingredients of a cosmetic formulation, and suitable for use
in contact with the tissue or organ of humans and animals without
excessive toxicity, irritation, allergic response, immunogenicity,
or other problems or complications, commensurate with a reasonable
benefit/risk ratio.
[0383] While it is possible for the active ingredient, e.g.,
ammonia oxidizing bacteria, e.g., N. eutropha, to be administered
alone, in many embodiments it present in a pharmaceutical
formulation or composition. Accordingly, this disclosure provides a
pharmaceutical formulation comprising ammonia oxidizing bacteria,
for example, N. eutropha and a pharmaceutically acceptable
excipient. Pharmaceutical compositions may take the form of a
pharmaceutical formulation as described below.
[0384] The pharmaceutical formulations described herein include
those suitable for oral, parenteral (including subcutaneous,
intradermal, intramuscular, intravenous, and intraarticular),
inhalation (including fine particle dusts or mists which may be
generated by means of various types of metered doses, pressurized
aerosols, nebulizers or insufflators, and including intranasally or
via the lungs), rectal and topical (including dermal, transdermal,
transmucosal, buccal, sublingual, and intraocular) administration,
although the most suitable route may depend upon, for example, the
condition and disorder of the recipient.
[0385] The formulations may conveniently be presented in unit
dosage form and may be prepared by any of the methods known in the
art of pharmacy. Typically, methods include the step of bringing
the active ingredient (e.g., ammonia oxidizing bacteria, e.g., N.
eutropha) into association with a pharmaceutical carrier which
constitutes one or more accessory ingredients. In general the
formulations are prepared by uniformly and intimately bringing into
association the active ingredient with liquid carriers or finely
divided solid carriers or both and then, if necessary, shaping the
product into the desired formulation.
[0386] Formulations may be presented as discrete units such as
capsules, cachets or tablets, each containing a predetermined
amount of, e.g., N. eutropha; as a powder or granules; as a
solution or a suspension in an aqueous liquid or a non-aqueous
liquid; or as an oil-in-water liquid emulsion or a water-in-oil
liquid emulsion. The active ingredient may also be presented as a
bolus, electuary or paste. Various pharmaceutically acceptable
carriers and their formulation are described in standard
formulation treatises, e.g., Remington's Pharmaceutical Sciences by
E. W. Martin. See also Wang, Y. J. and Hanson, M. A., Journal of
Parenteral Science and Technology, Technical Report No. 10, Supp.
42:2 S, 1988.
[0387] The ammonia oxidizing bacteria, e.g., N. eutropha
compositions can, for example, be administered in a form suitable
for immediate release or extended release. Suitable examples of
sustained-release systems include suitable polymeric materials, for
example semi-permeable polymer matrices in the form of shaped
articles, e.g., films, or microcapsules; suitable hydrophobic
materials, for example as an emulsion in an acceptable oil; or ion
exchange resins. Sustained-release systems may be administered
orally; rectally; parenterally; intracisternally; intravaginally;
intraperitoneally; topically, for example as a powder, ointment,
gel, drop or transdermal patch; bucally; or as a spray.
[0388] Preparations for administration can be suitably formulated
to give controlled release of ammonia oxidizing bacteria, e.g., N.
eutropha. For example, the pharmaceutical compositions may be in
the form of particles comprising one or more of biodegradable
polymers, polysaccharide jellifying and/or bioadhesive polymers, or
amphiphilic polymers. These compositions exhibit certain
biocompatibility features which allow a controlled release of an
active substance. See U.S. Pat. No. 5,700,486.
[0389] Exemplary compositions include suspensions which can
contain, for example, microcrystalline cellulose for imparting
bulk, alginic acid or sodium alginate as a suspending agent,
methylcellulose as a viscosity enhancer, dicalcium phosphate,
starch, magnesium stearate and/or lactose and/or other excipients,
binders, extenders, disintegrants, diluents and lubricants,
mannitol, lactose, sucrose and/or cyclodextrins. Also included in
such formulations may be high molecular weight excipients such as
celluloses (avicel) or polyethylene glycols (PEG). Such
formulations can also include an excipient to aid mucosal adhesion
such as hydroxy propyl cellulose (HPC), hydroxy propyl methyl
cellulose (HPMC), sodium carboxy methyl cellulose (SCMC), maleic
anhydride copolymer (e.g., Gantrez), and agents to control release
such as polyacrylic copolymer (e.g. Carbopol 934). Lubricants,
glidants, flavors, coloring agents and stabilizers may also be
added for ease of fabrication and use. The surfactant may be a
zwitterionic surfactant, a non-ionic surfactant, or an anionic
surfactant.
[0390] Excipients, such as surfactants that may be used with
embodiments of the present disclosure may include one or more of
cocamidopropyl betaine (ColaTeric COAB), polyethylene sorbitol
ester (e.g., Tween 80), ethoxylated lauryl alcohol (RhodaSurf 6
NAT), sodium laureth sulfate/lauryl glucoside/cocamidopropyl
betaine (Plantapon 611 L UP), sodium laureth sulfate (e.g.,
RhodaPex ESB 70 NAT), alkyl polyglucoside (e.g., Plantaren 2000 N
UP), sodium laureth sulfate (Plantaren 200), Dr. Bronner's Castile
soap, Dr. Bronner's Castile baby soap, Lauramine oxide (ColaLux
Lo), sodium dodecyl sulfate (SDS), polysulfonate alkyl
polyglucoside (PolySufanate 160 P), sodium lauryl sulfate
(Stepanol-WA Extra K). and combinations thereof. Dr. Bronner's
Castile soap and Dr. Bronner's baby soap comprises water, organic
coconut oil, potassium hydroxide, organic olive oil, organic fair
deal hemp oil, organic jojoba oil, citric acid, and tocopherol.
In some embodiments, surfactants may be used with ammonia oxidizing
bacteria in amounts that allow nitrite production to occur. In some
embodiments, the preparation may have less than about 0.0001% to
about 10% of surfactant. In some embodiments, the preparation may
have between about 0.1% and about 10% surfactant. In some
embodiments, the concentration of surfactant used may be between
about 0.0001% and about 10%. In some embodiments, the preparation
may be substantially free of surfactant.
[0391] In some embodiments, the formulation, e.g., preparation, may
include other components that may enhance effectiveness of ammonia
oxidizing bacteria, or enhance a treatment or indication.
[0392] In some embodiments, a chelator may be included in the
preparation. A chelator may be a compound that may bind with
another compound, e.g., a metal. The chelator may provide
assistance in removing an unwanted compound from an environment, or
may act in a protective manner to reduce or eliminate contact of a
particular compound with an environment, e.g., ammonia oxidizing
bacteria, e.g. a preparation of ammonia oxidizing bacteria, e.g.,
an excipient. In some embodiments, the preparation may be
substantially free of chelator.
[0393] Formulations may also contain anti-oxidants, buffers,
bacteriostats that prevent the growth of undesired bacteria,
solutes, and aqueous and non-aqueous sterile suspensions which may
include suspending agents and thickening agents. The formulations
may be presented in unit-dose or multi-dose containers, for example
sealed ampoules and vials, and may be stored in a freeze-dried
(lyophilised) condition requiring only the addition of a sterile
liquid carrier, for example saline or water-for-injection,
immediately prior to use. Extemporaneous solutions and suspensions
may be prepared from powders, granules and tablets of the kind
previously described. Exemplary compositions include solutions or
suspensions which can contain, for example, suitable non-toxic,
pharmaceutically acceptable diluents or solvents, such as mannitol,
1,3-butanediol, water, Ringer's solution, an isotonic sodium
chloride solution, or other suitable dispersing or wetting and
suspending agents, including synthetic mono- or diglycerides, and
fatty acids, including oleic acid, or Cremaphor. An aqueous carrier
may be, for example, an isotonic buffer solution at a pH of from
about 3.0 to about 8.0, a pH of from about 3.5 to about 7.4, for
example from 3.5 to 6.0, for example from 3.5 to about 5.0. Useful
buffers include sodium citrate-citric acid and sodium
phosphate-phosphoric acid, and sodium acetate/acetic acid buffers.
The composition in some embodiments does not include oxidizing
agents.
Excipients that can be included are, for instance, proteins, such
as human serum albumin or plasma preparations. If desired, the
pharmaceutical composition may also contain minor amounts of
non-toxic auxiliary substances, such as wetting or emulsifying
agents, preservatives, and pH buffering agents and the like, for
example sodium acetate or sorbitan monolaurate. In some
embodiments, excipients, e.g., a pharmaceutically acceptable
excipient or a cosmetically acceptable excipient, may comprise an
anti-adherent, binder, coat, disintegrant, filler, flavor, color,
lubricant, glidant, sorbent, preservative, or sweetener. In some
embodiments, the preparation may be substantially free of
excipients.
[0394] In some embodiments, the preparation may be substantially
free of one or more of the compounds or substances listed in the
disclosure.
[0395] Exemplary compositions for aerosol administration include
solutions in saline, which can contain, for example, benzyl alcohol
or other suitable preservatives, absorption promoters to enhance
bioavailability, and/or other solubilizing or dispersing agents.
Conveniently in compositions for aerosol administration the ammonia
oxidizing bacteria, e.g., N. eutropha is delivered in the form of
an aerosol spray presentation from a pressurized pack or a
nebulizer, with the use of a suitable propellant, e.g.,
dichlorodifluoro-methane, trichlorofluoromethane,
dichlorotetrafluoroethane, carbon dioxide or other suitable gas. In
the case of a pressurized aerosol the dosage unit can be determined
by providing a valve to deliver a metered amount. Capsules and
cartridges of e.g., gelatin can be formulated to contain a powder
mix of the N. eutropha and a suitable powder base, for example
lactose or starch. In certain embodiments, N. eutropha is
administered as an aerosol from a metered dose valve, through an
aerosol adapter also known as an actuator. Optionally, a stabilizer
is also included, and/or porous particles for deep lung delivery
are included (e.g., see U.S. Pat. No. 6,447,743).
[0396] Formulations may be presented with carriers such as cocoa
butter, synthetic glyceride esters or polyethylene glycol. Such
carriers are typically solid at ordinary temperatures, but liquefy
and/or dissolve at body temperature to release the ammonia
oxidizing bacteria, e.g., N. eutropha.
[0397] Exemplary compositions for topical administration include a
topical carrier such as Plastibase (mineral oil gelled with
polyethylene). In some aspects, the composition and/or excipient
may be in the form of one or more of a liquid, a solid, or a gel.
For example, liquid suspensions may include, but are not limited
to, water, saline, phosphate-buffered saline, or an ammonia
oxidizing storage buffer. Gel formulations may include, but are not
limited to agar, silica, polyacrylic acid (for example
Carbopol.RTM.), carboxymethyl cellulose, starch, guar gum, alginate
or chitosan. In some embodiments, the formulation may be
supplemented with an ammonia source including, but not limited to
ammonium chloride or ammonium sulfate.
[0398] In some embodiments, an ammonia oxidizing bacteria, e.g., N.
eutropha composition is formulated to improve NO penetration into
the skin. A gel-forming material such as KY jelly or various hair
gels would present a diffusion barrier to NO loss to ambient air,
and so improve the skin's absorption of NO. The NO level in the
skin will generally not greatly exceed 20 nM/L because that level
activates GC and would cause local vasodilatation and oxidative
destruction of excess NO.
[0399] It should be understood that in addition to the ingredients
particularly mentioned above, the formulations as described herein
may include other agents conventional in the art having regard to
the type of formulation in question.
[0400] The formulation, e.g., preparation, e.g., composition may be
provided in a container, delivery system, or delivery device,
having a weight, including or not including the contents of the
container, that may be less than about 50, 100, 200, 300, 400, 500,
600, 700, 800, 900, 1000, 1500, or 2000 grams.
[0401] Suitable unit dosage formulations are those containing an
effective dose, as hereinbefore recited, or an appropriate fraction
thereof, of ammonia oxidizing bacteria, e.g., N. eutropha.
[0402] A therapeutically effective amount of ammonia oxidizing
bacteria, e.g., N. eutropha may be administered as a single pulse
dose, as a bolus dose, or as pulse doses administered over time.
Thus, in pulse doses, a bolus administration of ammonia oxidizing
bacteria, e.g., N. eutropha is provided, followed by a time period
wherein ammonia oxidizing bacteria, e.g., N. eutropha is
administered to the subject, followed by a second bolus
administration. In specific, non-limiting examples, pulse doses are
administered during the course of a day, during the course of a
week, or during the course of a month.
[0403] In some embodiments, a preparation of ammonia oxidizing
bacteria, e.g., a formulation, e.g., a composition, may be applied
for a pre-determined number of days. This may be based, for
example, at least in part, on the severity of the condition or
disease, the response to the treatment, the dosage applied and the
frequency of the dose. For example, the preparation may be applied
for about 1-3, 3-5, 5-7, 7-9, 5-10, 10-14, 12-18, 12-21, 21-28,
28-35, 35-42, 42-49, 49-56, 46-63, 63-70, 70-77, 77-84, 84-91 days,
for about 1 month, for about 2 months, for about 3 months. In some
embodiments, the ammonia oxidizing bacteria is administered for an
indefinite period of time, e.g., greater than one year, greater
than 5 years, greater than 10 years, greater than 15 years, greater
than 30 years, greater than 50 years, greater than 75 years. In
certain aspects, the preparation may be applied for about 16
days.
[0404] In some embodiments, a preparation of ammonia oxidizing
bacteria, e.g., a formulation, e.g., a composition, may be applied
a pre-determined number of times per day. This may be based, for
example, at least in part, on the severity of the condition or
disease, the response to the treatment, the dosage applied and the
frequency of the dose. For example, the preparation may be applied
1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19,
20, 21, 22, 23, 24 times per day.
[0405] In some embodiments, the preparation may be applied one time
per day. In other embodiments, the preparation may be applied two
times per day. In some embodiments, the preparation may be applied
a first pre-determined amount for a certain number of days, and a
second pre-determined amount for a certain subsequent number of
days. In some embodiments, the preparation may be applied for about
16 days.
[0406] Consumer Products
[0407] Ammonia oxidizing bacteria, e.g., N. eutropha may be
associated with a variety of consumer products, and examples of
such products are set out below. In some embodiments, the ammonia
oxidizing bacteria, e.g., N. eutropha associated with a product is
admixed with the product, for example, spread evenly throughout the
product, and in some embodiments, ammonia oxidizing bacteria, e.g.,
the N. eutropha associated with a product is layered on the
product.
[0408] In some embodiments, ammonia oxidizing bacteria, e.g., N.
eutropha is associated with a powder. Powders are typically small
particulate solids that are not attached to each other and that can
flow freely when tilted. Exemplary powders for consumer use include
talcum powder and some cosmetics (e.g., powder foundation).
[0409] In some embodiments, the ammonia oxidizing bacteria is
associated with a cosmetic. The cosmetic may be a substance for
topical application intended to alter a person's appearance, e.g.,
a liquid foundation, a powder foundation, blush, or lipstick. The
cosmetic may be any substance recited in the Food and Drug
Administration regulations, e.g., under 21 C.F.R. .sctn.720.4.
[0410] The cosmetic may be at least one of a baby product, e.g., a
baby shampoo, a baby lotion, a baby oil, a baby powder, a baby
cream; a bath preparation, e.g., a bath oil, a tablet, a salt, a
bubble bath, a bath capsule; an eye makeup preparation, e.g., an
eyebrow pencil, an eyeliner, an eye shadow, an eye lotion, an eye
makeup remover, a mascara; a fragrance preparation, e.g., a
colognes, a toilet water, a perfume, a powder (dusting and talcum),
a sachet; hair preparations, e.g., hair conditioners, hair sprays,
hair straighteners, permanent waves, rinses, shampoos, tonics,
dressings, hair grooming aids, wave sets; hair coloring
preparations, e.g., hair dyes and colors, hair tints, coloring hair
rinses, coloring hair shampoos, hair lighteners with color, hair
bleaches; makeup preparations, e.g., face powders, foundations, leg
and body paints, lipstick, makeup bases, rouges, makeup fixatives;
manicuring preparations, e.g., basecoats and undercoats, cuticle
softeners, nail creams and lotions, nail extenders, nail polish and
enamel, nail polish and enamel removers; oral hygiene products,
e.g., dentrifices, mouthwashes and breath fresheners; bath soaps
and detergents, deodorants, douches, feminine hygiene deodorants;
shaving preparations, e.g., aftershave lotions, beard softeners,
talcum, preshave lotions, shaving cream, shaving soap; skin care
preparations, e.g., cleansing, depilatories, face and neck, body
and hand, foot powders and sprays, moisturizing, night
preparations, paste masks, skin fresheners; and suntan
preparations, e.g., gels, creams, and liquids, and indoor tanning
preparations.
[0411] In some embodiments, the formulations, compositions, or
preparations described herein, may comprise, be provided as, or
disposed in at least one of a baby product, e.g., a baby shampoo, a
baby lotion, a baby oil, a baby powder, a baby cream; a bath
preparation, e.g., a bath oil, a tablet, a salt, a bubble bath, a
bath capsule; a powder (dusting and talcum), a sachet; hair
preparations, e.g., hair conditioners, rinses, shampoos, tonics,
face powders, cuticle softeners, nail creams and lotions, oral
hygiene products, mouthwashes, bath soaps, douches, feminine
hygiene deodorants; shaving preparations, e.g., aftershave lotions,
skin care preparations, e.g., cleansing, face and neck, body and
hand, foot powders and sprays, moisturizing, night preparations,
paste masks, skin fresheners; and suntan preparations, e.g., gels,
creams, and liquids.
In some embodiments, ammonia oxidizing bacteria, e.g., N. eutropha
is associated with a cosmetic. The cosmetic may be a substance for
topical application intended to alter a person's appearance, e.g.,
a liquid foundation, a powder foundation, blush, or lipstick. Other
components may be added to these cosmetic preparations as selected
by one skilled in the art of cosmetic formulation such as, for
example, water, mineral oil, coloring agent, perfume, aloe,
glycerin, sodium chloride, sodium bicarbonate, pH buffers, UV
blocking agents, silicone oil, natural oils, vitamin E, herbal
concentrates, lactic acid, citric acid, talc, clay, calcium
carbonate, magnesium carbonate, zinc oxide, starch, urea, and
erythorbic acid, or any other excipient known by one of skill in
the art, including those disclosed herein.
[0412] In some embodiments, the preparation may be disposed in, or
provided as, a powder, cosmetic, cream, stick, aerosol, salve,
wipe, or bandage.
[0413] In some embodiments, ammonia oxidizing bacteria, e.g., N.
eutropha is associated with a cream. The cream may be a fluid
comprising a thickening agent, and generally has a consistency that
allows it to be spread evenly on the skin. Exemplary creams include
moisturizing lotion, face cream, and body lotion.
[0414] In some embodiments, ammonia oxidizing bacteria, e.g., the
N. eutropha is associated with a stick. A stick is typically a
solid that, when placed in contact with a surface, transfers some
of the stick contents to the surface. Exemplary sticks include
deodorant stick, lipstick, lip balm in stick form, and sunscreen
applicator sticks.
[0415] In some embodiments, ammonia oxidizing bacteria, e.g., the
N. eutropha is associated with an aerosol. An aerosol is typically
a colloid of fine solid particles or fine liquid droplets, in a gas
such as air. Aerosols may be created by placing the N. eutropha
(and optionally carriers) in a vessel under pressure, and then
opening a valve to release the contents. The container may be
designed to only exert levels of pressure that are compatible with
N. eutropha viability. For instance, the high pressure may be
exerted for only a short time, and/or the pressure may be low
enough not to impair viability. Examples of consumer uses of
aerosols include for sunscreen, deodorant, perfume, hairspray, and
insect repellant.
[0416] In some embodiments, ammonia oxidizing bacteria, e.g., the
N. eutropha is associated with a salve. A salve may be a topically
applied agent with a liquid or cream-like consistency, intended to
protect the skin or promote healing. Examples of salves include
burn ointments and skin moisturizers.
[0417] In some embodiments, ammonia oxidizing bacteria, e.g., the
N. eutropha is associated with a wipe. A wipe may be a flexible
material suitable for topically applying a liquid or cream onto
skin. The wipe may be, e.g., paper-based or cloth based. Exemplary
wipes include tissues and wet wipes.
[0418] The compositions comprising ammonia oxidizing bacteria,
e.g., N. eutropha may also comprise one or more of a moisturizing
agent, deodorizing agent, scent, colorant, insect repellant,
cleansing agent, or UV-blocking agent.
[0419] For instance, the moisturizing agent may be an agent that
reduces or prevents skin dryness. Exemplary moisturizing agents
include humectants (e.g., urea, glycerin, alpha hydroxy acids and
dimethicone) and emollients (e.g., lanolin, mineral oil and
petrolatum). Moisturizing agents may be included, e.g., in ammonia
oxidizing bacteria, e.g., N. eutropha-containing creams, balms,
lotions, or sunscreen.
[0420] A deodorizing agent may be an agent that reduces unwanted
odors. A deodorizing agent may work by directly neutralizing odors,
preventing perspiration, or preventing the growth of odor-producing
bacteria. Exemplary deodorizing agents include aluminum salts
(e.g., aluminum chloride or aluminum chlorohydrate),
cyclomethicone, talc, baking soda, essential oils, mineral salts,
hops, and witch hazel. Deodorizing agents are typically present in
spray or stick deodorants, and can also be found in some soaps and
clothing.
[0421] An insect repellant may be an agent that can be applied to
surfaces (e.g., skin) that discourage insects and other arthropods
from lighting on the surface. Insect repellants include DEET
(N,N-diethyl-m-toluamide), p-menthane-3,8-diol (PMD), icaridin,
nepetalactone, citronella oil, neem oil, bog myrtle, dimethyl
carbate, Tricyclodecenyl allyl ether, and IR3535
(3-[N-Butyl-N-acetyl]-aminopropionic acid, ethyl ester).
[0422] A cleansing agent may be an agent that removes dirt or
unwanted bacteria from a surface like skin. Exemplary cleansing
agents include bar soaps, liquid soaps, and shampoos.
[0423] A UV-blocking agent may be an agent that can be applied to a
surface to reduce the amount of ultraviolet light the surface
receives. A UV-blocking agent may block UV-A and/or UV-B rays. A UV
blocking agent can function by absorbing, reflecting, or scattering
UV. Exemplary UV-blocking agents include absorbers, e.g.,
homosalate, octisalate (also called octyl salicylate), octinoxate
(also called octyl methoxycinnamate or OMC), octocrylene,
oxybenzone, and avobenzone, and reflectors (e.g., titanium dioxide
and zinc oxide). UV-blocking agents are typically presents in
sunscreens, and can also be found in skin creams and some
cosmetics.
[0424] In some embodiments, ammonia oxidizing bacteria, e.g., N.
eutropha is associated with a conditioner. Conditioner generally
refers to a substance with cream-like consistency that can be
applied to hair to improve its appearance, strength, or
manageability.
[0425] In some embodiments, ammonia oxidizing bacteria, e.g., N.
eutropha is associated with cloth. Cloth generally refers to a
flexible material suitable to be made into clothing, e.g., having
enough material strength to withstand everyday motion by a wearer.
Cloth can be fibrous, woven, or knit; it can be made of a naturally
occurring material or a synthetic material. Exemplary cloth
materials include cotton, flax, wool, ramie, silk, denim, leather,
nylon, polyester, and spandex, and blends thereof.
[0426] In some embodiments, ammonia oxidizing bacteria, e.g., N.
eutropha is associated with yarn. Yarn generally refers to a long,
thin spun flexible material that is suitable for knitting or
weaving. Yarn can be made of, e.g., wool, cotton, polyester, and
blends thereof.
[0427] In some embodiments, ammonia oxidizing bacteria, e.g., N.
eutropha is associated with thread. Thread generally refers to a
long, thin spun flexible material that is suitable for sewing.
Thread generally has a thinner diameter than yarn. Thread can be
made of, e.g., cotton, polyester, nylon, silk, and blends
thereof.
[0428] Articles of clothing such as, for example, shoes, shoe
inserts, pajamas, sneakers, belts, hats, shirts, underwear,
athletic garments, helmets, towels, gloves, socks, bandages, and
the like, may also be treated with ammonia oxidizing bacteria,
e.g., N. eutropha. Bedding, including sheets, pillows, pillow
cases, and blankets may also be treated with ammonia oxidizing
bacteria, e.g., N. eutropha. In some embodiments, areas of skin
that cannot be washed for a period of time may also be contacted
with ammonia oxidizing bacteria, e.g., N. eutropha. For example,
skin enclosed in orthopedic casts which immobilize injured limbs
during the healing process, and areas in proximity to injuries that
must be kept dry for proper healing such as stitched wounds may
benefit from contact with the ammonia oxidizing bacteria, e.g., N.
eutropha.
[0429] In some aspects, the present disclosure provides a wearable
article comprising an N. eutropha strain as described herein. A
wearable article may be a light article that can be closely
associated with a user's body, in a way that does not impede
ambulation. Examples of wearable articles include a wristwatch,
wristband, headband, hair elastic, hair nets, shower caps, hats,
hairpieces, and jewelry. The wearable article comprising an ammonia
oxidizing bacteria, e.g., N. eutropha strain described herein may
provide, e.g., at a concentration that provides one or more of a
treatment or prevention of a skin disorder, a treatment or
prevention of a disease or condition associated with low nitrite
levels, a treatment or prevention of body odor, a treatment to
supply nitric oxide to a subject, or a treatment to inhibit
microbial growth.
[0430] In some embodiments, the ammonia oxidizing bacteria, e.g.,
N. eutropha is associated with a product intended to contact the
hair, for example, a brush, comb, shampoo, conditioner, headband,
hair elastic, hair nets, shower caps, hats, and hairpieces. Nitric
oxide formed on the hair, away from the skin surface, may be
captured in a hat, scarf or face mask and directed into inhaled
air.
[0431] Articles contacting the surface of a human subject, such as
a diaper, may be associated with ammonia oxidizing bacteria, e.g.,
N. eutropha. Because diapers are designed to hold and contain urine
and feces produced by incontinent individuals, the urea in urine
and feces can be hydrolyzed by skin and fecal bacteria to form free
ammonia which is irritating and may cause diaper rash.
Incorporation of bacteria that metabolize urea into nitrite or
nitrate, such as ammonia oxidizing bacteria, e.g., N. eutropha, may
avoid the release of free ammonia and may release nitrite and
ultimately NO which may aid in the maintenance of healthy skin for
both children and incontinent adults. The release of nitric oxide
in diapers may also have anti-microbial effects on disease causing
organisms present in human feces. This effect may continue even
after disposable diapers are disposed of as waste and may reduce
the incidence of transmission of disease through contact with
soiled disposable diapers
[0432] In some embodiments, the product comprising ammonia
oxidizing bacteria, e.g., N. eutropha is packaged. The packaging
may serve to compact the product or protect it from damage, dirt,
or degradation. The packaging may comprise, e.g., plastic, paper,
cardboard, or wood. In some embodiments the packaging is
impermeable to bacteria. In some embodiments the packaging is
permeable to oxygen and/or carbon dioxide.
5. METHODS OF TREATMENT WITH N. EUTROPHA
[0433] The present disclosure provides various methods of treating
diseases and conditions using ammonia oxidizing bacteria, e.g., N.
eutropha. The ammonia oxidizing bacteria, e.g., N. eutropha that
may be used to treat diseases and conditions include all the
ammonia oxidizing bacteria, e.g., N. eutropha compositions
described in this application, e.g. a purified preparation of
optimized ammonia oxidizing bacteria, e.g., N. eutropha, e.g. those
in Section 2 above, for instance strain D23.
[0434] For instance, the disclosure provides uses, for treating a
condition or disease (e.g., inhibiting microbial growth on a
subject's skin), an optionally axenic composition of N. eutropha
comprising a nucleic acid sequence at least about 70%, 80%, 85%,
90%, 95%, 96%, 97%, 98%, 99%, or 99.5% identical to SEQ ID NO: 1;
an optionally axenic composition of N. eutropha comprising a
nucleic acid sequence at least about 70%, 80%, 85%, 90%, 95%, 96%,
97%, 98%, 99%, or 99.5% identical to any one of the strain D23
nucleic acids of Table 1. In embodiments, the N. eutropha comprises
at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or all
of the strain D23 nucleic acids of Table 1. In embodiments, the N.
eutropha comprises one or more nucleic acids of FIGS. 6-8. As a
further example, this disclosure provides uses, for treating a
condition or disease, an optionally axenic composition of N.
eutropha comprising an amino acid sequence at least about 70%, 80%,
85%, 90%, 95%, 96%, 97%, 98%, 99%, or 99.5% identical to any one of
the strain D23 protein sequences of Table 1. In embodiments, the N.
eutropha comprises at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,
13, 14, 15, or all of the strain D23 protein sequences of Table 1.
In embodiments, the N. eutropha comprises one or more proteins
encoded by the nucleic acids of FIGS. 6-8. The N. eutropha of this
paragraph may be used to treat, e.g., diabetic ulcers, e.g.,
diabetic foot ulcers, chronic wounds, acne, rosacea, eczema, or
psoriasis.
[0435] In certain embodiments, the disclosure provides uses, for
treating a condition or disease (e.g., inhibiting microbial growth
on a subject's skin), an optionally axenic composition of N.
eutropha having one or more of: (1) an optimized growth rate, (2)
an optimized NH.sub.4.sup.+ oxidation rate, (3) an optimized
resistance to NH.sub.3, (4) an optimized resistance to,
NH.sub.4.sup.+, and (5) an optimized resistance to, NO.sub.2.sup.-.
For instance, the axenic N. eutropha composition may have
properties (1) and (2); (2) and (3); (3) and (4); or (4) and (5)
from the list at the beginning of this paragraph. As another
example, the axenic N. eutropha composition may have properties
(1), (2), and (3); (1), (2), and (4); (1), (2), and (5); (1), (3),
and (4); (1), (3), and (5); (1), (4), and (5); (2), (3), and (4);
(2), (3), and (5), or (3), (4), and (5) from the list at the
beginning of this paragraph. As a further example, the optionally
axenic N. eutropha composition may have properties (1), (2), (3),
and (4); (1), (2), (3), and (5); (1), (2), (4), and (5); (1), (3),
(4), and (5); or (2), (3), (4), and (5) from the list at the
beginning of this paragraph. In some embodiments, the axenic N.
eutropha composition has properties (1), (2), (3), (4), and (5)
from the list at the beginning of this paragraph. The N. eutropha
of this paragraph may be used to treat, e.g., diabetic ulcers,
e.g., diabetic foot ulcers, chronic wounds, acne, rosacea, eczema,
or psoriasis.
[0436] In some embodiments, optionally axenic N. eutropha (e.g.,
strain D23) are used to treat a subject. Subjects may include an
animal, a mammal, a human, a non-human animal, a livestock animal,
or a companion animal.
[0437] In some embodiments, optionally axenic N. eutropha described
herein (e.g., the N. eutropha described in this Section and in
Section 2 above, e.g., strain D23) are used to inhibit the growth
of other organisms. For instance, N. eutropha D23 is well-adapted
for long-term colonization of human skin, and in some embodiments
it out-competes other bacteria that are undesirable on the skin.
Undesirable skin bacteria include, e.g., those that can infect
wounds, raise the risk or severity of a disease, or produce odors.
Certain undesirable skin bacteria include S. aureus, P. aeruginosa,
S. pyogenes, and A. baumannii. The N. eutropha described herein may
out-compete other organisms by, e.g., consuming scarce nutrients,
or generating byproducts that are harmful to other organisms, e.g.,
changing the pH of the skin to a level that is not conducive to the
undesirable organism's growth.
[0438] Accordingly, the present disclosure provides, inter alia, a
method of inhibiting microbial growth on a subject's skin,
comprising topically administering to a human in need thereof an
effective dose of optionally axenic N. eutropha bacteria as
described herein (e.g., strain D23). Similarly, the present
disclosure provides optionally axenic N. eutropha as described
herein (e.g., strain D23) for use in inhibiting microbial growth on
a subject's skin. Likewise, the present disclosure provides a use
of optionally axenic N. eutropha (e.g., strain D23) in the
manufacture of a medicament for inhibiting microbial growth on a
subject's skin.
[0439] The present disclosure also provides a method of supplying
nitric oxide to a subject, comprising positioning an effective dose
of optionally axenic N. eutropha bacteria described herein (e.g.,
strain D23) in close proximity to the subject. Similarly, the
present disclosure provides optionally axenic N. eutropha (e.g.,
strain D23) as described herein for use in supplying nitric oxide
to a subject. Likewise, the present disclosure provides a use of
optionally axenic N. eutropha (e.g., strain D23) in the manufacture
of a medicament or composition suitable for position in close
proximity to a subject.
[0440] The present disclosure also provides a method of reducing
body odor, comprising topically administering to a subject in need
thereof an effective dose of optionally axenic N. eutropha bacteria
described herein (e.g., strain D23). Similarly, the present
disclosure provides optionally axenic N. eutropha as described
herein (e.g., strain D23) for use in reducing body odor in a
subject. Likewise, the present disclosure provides a use of
optionally axenic N. eutropha as described herein (e.g., strain
D23) in the manufacture of a medicament or composition for reducing
body odor.
[0441] The present disclosure also provides a method of treating or
preventing a disease associated with low nitrite levels, comprising
topically administering to a subject in need thereof a
therapeutically effective dose of optionally axenic N. eutropha
bacteria described herein (e.g., strain D23). Similarly, the
present disclosure provides a topical formulation of optionally
axenic N. eutropha as described herein (e.g., strain D23) for use
in treating a disease associated with low nitrite levels. Likewise,
the present disclosure provides a use of optionally axenic N.
eutropha as described herein (e.g., strain D23) in the manufacture
of a topical medicament for treating a disease associated with low
nitrite levels.
[0442] The present disclosure also provides a method of treating or
preventing a skin disorder or skin infection, comprising topically
administering to a subject in need thereof a therapeutically
effective dose of optionally axenic N. eutropha bacteria as
described herein (e.g., strain D23). Similarly, the present
disclosure provides optionally axenic N. eutropha as described
herein (e.g., strain D23) for use in treating a skin disorder in a
subject. Likewise, the present disclosure provides a use of
optionally axenic N. eutropha as described herein (e.g., strain
D23) in the manufacture of a medicament for treating skin disorder.
In embodiments, the skin disorder is acne, rosacea, eczema,
psoriasis, or urticaria; the skin infection is impetigo.
[0443] While not wishing to be bound by theory, it is proposed that
treatment of acne with a therapeutically effective dose of
optionally axenic N. eutropha bacteria as described herein (e.g.,
strain D23) may involve the downregulation of inflammation due to
NO generation; and/or limiting and/or inhibiting the spread and
proliferation of Propionibacterium acnes associated with acne
vulgaris through acidified nitrite and NO production.
[0444] For instance, the disclosure provides uses, for treating a
condition or disease (e.g., inhibiting microbial growth on a
subject's skin), a composition of ammonia oxidizing bacteria. In
embodiments, the ammonia oxidizing bacteria may be used to treat,
e.g., chronic wounds, acne, rosacea, eczema, psoriasis, uticaria,
skin infections, or diabetic ulcers, e.g., diabetic foot
ulcers.
[0445] The systems and methods of the present disclosure may
provide for, or contain contents, to be useful for treating or
preventing a skin disorder, treating or preventing a disease or
condition associated with low nitrite levels, a treating or
preventing body odor, treating to supply nitric oxide to a subject,
or treating to inhibit microbial growth.
[0446] The systems and methods of the present disclosure may
provide for reducing an amount of undesirable bacteria from an
environment, e.g., a surface of a subject.
[0447] The systems and methods of the present disclosure may
provide for, or contain contents, to be useful in a treatment of at
least one of HIV dermatitis, infection in a diabetic foot ulcer,
atopic dermatitis, acne, eczema, contact dermatitis, allergic
reaction, psoriasis, uticaria, rosacea, skin infections, vascular
disease, vaginal yeast infection, a sexually transmitted disease,
heart disease, atherosclerosis, baldness, leg ulcers secondary to
diabetes or confinement to bed, angina, particularly chronic,
stable angina pectoris, ischemic diseases, congestive heart
failure, myocardial infarction, ischemia reperfusion injury,
laminitis, hypertension, hypertrophic organ degeneration, Raynaud's
phenomenon, fibrosis, fibrotic organ degeneration, allergies,
autoimmune sensitization, end stage renal disease, obesity,
impotence, pneumonia, primary immunodeficiency, epidermal lysis
bulosa, or cancer.
[0448] The systems and methods of the present disclosure may
provide for, or contain contents, to be useful in a treatment of at
least one of acne, eczema, psoriasis, uticaria, rosacea, skin
infections and wounds, e.g., an infected wound.
[0449] In some embodiments, ammonia oxidizing bacteria may be used
to treat a subject. Subjects may include an animal, a mammal, a
human, a non-human animal, a livestock animal, or a companion
animal.
[0450] In some embodiments, ammonia oxidizing bacteria described
herein are used to inhibit the growth of other organisms. For
instance, ammonia oxidizing bacteria may be well-adapted for
long-term colonization of human skin, and in some embodiments it
out-competes other bacteria that are undesirable on the skin.
Undesirable skin bacteria include, e.g., those that can infect
wounds, raise the risk or severity of a disease, or produce odors.
Undesirable bacteria may be referred to as pathogenic bacteria.
Certain undesirable skin bacteria include Staphylococcus aureus (S.
aureus), e.g., methicillin resistant Staphylococcus aureus
Pseudomonas aeruginosa (P. aeruginosa), Streptococcus pyogenes (S.
pyogenes), Acinetobacter baumannii (A. baumannii),
Propionibacteria, and Stenotrophomonas. The ammonia oxidizing
bacteria described herein may out-compete other organisms by, e.g.,
consuming scarce nutrients, or generating byproducts that are
harmful to other organisms, e.g., changing the pH of the skin to a
level that is not conducive to the undesirable organism's
growth.
[0451] Accordingly, the present disclosure provides, inter alia, a
method of inhibiting microbial growth on a subject's skin,
comprising topically administering to a human in need thereof an
effective dose of ammonia oxidizing bacteria as described herein.
Similarly, the present disclosure provides ammonia oxidizing
bacteria as described herein for use in inhibiting microbial growth
on a subject's skin. Likewise, the present disclosure provides a
use of ammonia oxidizing bacteria in the manufacture of a
medicament for inhibiting microbial growth on a subject's skin.
[0452] The present disclosure provides, inter alia, a method of
changing a composition of a skin microbiome, e.g., modulating a
composition of a skin microbiome, e.g., modulating or changing the
proportions of the skin microbiome, in an environment, e.g., a
surface, e.g., a surface of a subject. The method may comprise
administering, e.g., applying, a preparation comprising ammonia
oxidizing bacteria to an environment, e.g., a surface, e.g., a
surface of a subject. In some embodiments, the amount and frequency
of administration, e.g., application, may be sufficient to reduce
the proportion of pathogenic bacteria on the surface of the skin.
In some embodiments, the subject may be selected on the basis of
the subject being in need of a reduction in the proportion of
pathogenic bacteria on the surface of the skin.
[0453] The present disclosure may further provide obtaining a
sample from the surface of the skin, and isolating DNA of bacteria
in the sample. Sequencing of the DNA of bacteria in the sample may
also be performed to determine or monitor the amount or proportion
of bacteria in a sample of a subject.
[0454] The present disclosure may also provide for increasing the
proportion of non-pathogenic bacteria on the surface. In some
embodiments, the non-pathogenic bacteria may be commensal
non-pathogenic bacteria. In some embodiments, the non-pathogenic
bacteria may be of the Staphylococcus genus. In some embodiments,
the non-pathogenic bacteria may be Staphylococcus epidermidis. In
some embodiments, the non-pathogenic bacteria that is increased in
proportion may be of the Staphylococcus genus, comprising at least
about 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%,
70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100%
Staphylococcus epidermidis.
[0455] The increase in the proportion of non-pathogenic bacteria
may occur with a pre-determined period of time, e.g., in less than
1 day, 2 days, 3 days, 4 days, 5 days, 1 week, 2 weeks, 3 weeks, or
4 weeks, or in less than 1-3, 3-5, 5-7, 7-9, 5-10, 10-14, 12-18,
12-21, 21-28, 28-35, 35-42, 42-49, 49-56, 46-63, 63-70, 70-77,
77-84, 84-91 days.
[0456] The increase in the proportion of Staphylococcus bacteria,
e.g., Staphylococcus epidermidis, may be observed in less than
about 3 weeks, e.g., about 16 days, e.g., about 2 weeks.
[0457] The present disclosure may provide for decreasing the
proportion of pathogenic bacteria, e.g., potentially pathogenic
bacteria, e.g., disease-associated bacteria on the surface. In some
embodiments, the pathogenic bacteria may be Propionibacteria. In
some embodiments, the pathogenic bacteria may be
Stenotrophomonas.
[0458] The decrease in the proportion of pathogenic bacteria may
occur with a pre-determined period of time, e.g., in less than 1
day, 2 days, 3 days, 4 days, 5 days, 1 week, 2 weeks, 3 weeks, or 4
weeks, or in less than 1-3, 3-5, 5-7, 7-9, 5-10, 10-14, 12-18,
12-21, 21-28, 28-35, 35-42, 42-49, 49-56, 46-63, 63-70, 70-77,
77-84, 84-91 days.
[0459] The decrease in the proportion of Propionibacteria bacteria
and/or Stenotrophomonas may be observed in less than about 3 weeks,
e.g., about 16 days, e.g., about 2 weeks.
[0460] The present disclosure also provides a method of supplying
nitric oxide to a subject, comprising positioning an effective dose
of ammonia oxidizing bacteria described herein in close proximity
to the subject. Similarly, the present disclosure provides ammonia
oxidizing bacteria as described herein for use in supplying nitric
oxide to a subject. Likewise, the present disclosure provides a use
of in the manufacture of a medicament or composition suitable for
position in close proximity to a subject.
[0461] The present disclosure also provides a method of reducing
body odor, comprising topically administering to a subject in need
thereof an effective dose of ammonia oxidizing bacteria described
herein. Similarly, the present disclosure provides ammonia
oxidizing bacteria as described herein for use in reducing body
odor in a subject. Likewise, the present disclosure provides a use
of ammonia oxidizing bacteria as described herein in the
manufacture of a medicament or composition for reducing body
odor.
[0462] The present disclosure also provides a method of treating or
preventing a disease associated with low nitrite levels, comprising
topically administering to a subject in need thereof a
therapeutically effective dose of ammonia oxidizing bacteria
described herein. Similarly, the present disclosure provides a
topical formulation of ammonia oxidizing bacteria as described
herein for use in treating a disease associated with low nitrite
levels. Likewise, the present disclosure provides a use of ammonia
oxidizing bacteria as described herein in the manufacture of a
topical medicament for treating a disease associated with low
nitrite levels.
[0463] The present disclosure also provides a method of treating or
preventing a skin disorder or skin infection, comprising topically
administering to a subject in need thereof a therapeutically
effective dose of ammonia oxidizing bacteria as described herein.
Similarly, the present disclosure provides ammonia oxidizing
bacteria as described herein for use in treating a skin disorder in
a subject. Likewise, the present disclosure provides a use of
ammonia oxidizing bacteria as described herein in the manufacture
of a medicament for treating skin disorder. In embodiments, the
skin disorder is acne, rosacea, eczema, psoriasis, or urticaria;
the skin infection is impetigo.
[0464] While not wishing to be bound by theory, it is proposed that
treatment of rosacea with a therapeutically effective dose of
optionally axenic N. eutropha bacteria as described herein (e.g.,
strain D23) may involve downregulation due to NO generation. This
may be due to expression of Kazal-type KLK5/KLK7 inhibitor(s) that
may reduce formation of the human cathelicidin peptide LL-37 from
its precursor propeptide hCAP18.
[0465] While not wishing to be bound by theory, it is proposed that
treatment of eczema and/or atopic dermatitis with a therapeutically
effective dose of optionally axenic N. eutropha bacteria as
described herein (e.g., strain D23) may involve downregulation of
inflammation due to NO generation; and/or limiting and/or
inhibiting the spread and proliferation of S. aureus and other skin
pathogens often associated with very high colonization rates and
skin loads in atopic dermatitis through acidified nitrite and NO
production.
[0466] While not wishing to be bound by theory, it is proposed that
treatment of psoriasis with a therapeutically effective dose of
optionally axenic N. eutropha bacteria as described herein (e.g.,
strain D23) may involve downregulation of inflammation due to NO
generation and reduction in formation of human cathelicidin peptide
LL-37.
[0467] While not wishing to be bound by theory, it is proposed that
treatment of psoriasis with a therapeutically effective dose of
optionally axenic N. eutropha bacteria as described herein (e.g.,
strain D23) may involve downregulation of inflammation due to NO
generation.
[0468] While not wishing to be bound by theory, it is proposed that
treatment of impetigo or other skin and soft tissue infections with
a therapeutically effective dose of optionally axenic N. eutropha
bacteria as described herein (e.g., strain D23) may involve
limiting and/or inhibiting the spread and proliferation of S.
aureus and S. pyogenes.
[0469] The present disclosure also provides a method of promoting
wound healing, comprising administering to a wound an effective
dose of optionally axenic N. eutropha bacteria as described herein
(e.g., strain D23). Similarly, the present disclosure provides
optionally axenic N. eutropha as described herein (e.g., strain
D23) for use in treating a wound. Likewise, the present disclosure
provides a use of optionally axenic N. eutropha as described herein
(e.g., strain D23) in the manufacture of a medicament or a
composition for treating a wound.
[0470] Optionally axenic N. eutropha as described herein (e.g.,
strain D23) may be used to promote wound healing in a patient that
has an impaired healing ability, e.g., a diabetic patient.
[0471] In some embodiments, this disclosure provides methods of
using optionally axenic N. eutropha as described herein (e.g.,
strain D23) to prevent a disease or disorder, e.g., a skin
disorder. Prevention, in certain embodiments, means reducing the
risk of a subject developing a disease, compared to a similar
untreated subject. The risk need not be reduced to zero.
[0472] Individuals having a reduced bathing frequency, such as
astronauts, submarine crew members, military personnel during a
campaign, civilian workers in remote locations, refugees, bedridden
individuals and many others may maintain healthier skin by
maintaining N. eutropha on the skin. With regard to bedridden
individuals, the N. eutropha in some embodiments reduces the
frequency or severity of bed sores by augmenting inadequate
circulation.
[0473] It is appreciated that many modern degenerative diseases may
be caused by a lack of NO species, and that AOB on the external
skin can supply those species by diffusion, and that application of
AOB to the skin resolves long standing medical conditions. In
certain embodiments, AOB are applied to a subject to offset modern
bathing practices, especially with anionic detergents remove AOB
from the external skin.
[0474] One suitable method of topical application to apply
sufficient N. eutropha and then wear sufficient clothing so as to
induce sweating. However, many people will want to derive the
benefits of AOB while maintaining their current bathing habits, in
which case, a culture of the bacteria can be applied along with
sufficient substrate for them to produce NO. A nutrient solution
approximating the inorganic composition of human sweat can be used
for this purpose. Using bacteria adapted to media approximating
human sweat minimizes the time for them to adapt when applied.
Since sweat evaporates once excreted onto the skin surface, using a
culture media that has a higher ionic strength is desirable. A
concentration approximately twice that of human sweat is suitable,
but other conditions are also contemplated. AOB's nutritional needs
are typically met with NH.sub.3 or urea, O.sub.2, CO.sub.2, and
minerals. In some embodiments, the substrate comprises trace
minerals including iron, copper, zinc, cobalt, molybdenum,
manganese, sodium, potassium, calcium, magnesium, chloride,
phosphate, sulfate, or any combination thereof.
[0475] In some embodiments, the present disclosure provides a
method of treating a wound by applying a bandage comprising N.
eutropha to the wound. Also provided are methods of producing such
a bandage. The bandage may comprise, for example, an adhesive
portion to affix the bandage to undamaged skin near the wound and a
soft, flexible portion to cover or overlay the wound. In some
embodiments, the bandage contains no other organisms but N.
eutropha. The bandage may be made of a permeable material that
allows gasses like oxygen and carbon dioxide to reach the N.
eutropha when the bandage is applied to the wound. In certain
embodiments, the bandage comprises nutrients for N. eutropha such
as ammonium, ammonia, urea, or trace minerals. In certain
embodiments, the bandage comprises an antibiotic to which the N.
eutropha is resistant. The antibiotic resistance may arise from one
or more endogenous resistance gene or from one or more
transgenic.
[0476] In some embodiments, the N. eutropha is administered at a
dose of about 10.sup.8-10.sup.9 CFU, 10.sup.9-10.sup.10 CFU,
10.sup.10-10.sup.11 CFU, or 10.sup.11-10.sup.12 CFU per
application. In some embodiments, the N. eutropha is administered
topically at a dose of about 10.sup.10-10.sup.11 CFU, e.g., about
1.times.10.sup.10-5.times.10.sup.10,
1.times.10.sup.10-3.times.10.sup.10, or
1.times.10.sup.10-2.times.10.sup.10 CFU.
[0477] In some embodiments, the N. eutropha is administered in a
volume of about 1-2, 2-5, 5-10, 10-15, 12-18, 15-20, 20-25, or
25-50 ml per dose. In some embodiments, the solution is at a
concentration of about 10.sup.8-10.sup.9, 10.sup.9-10.sup.10, or
10.sup.10-10.sup.11 CFUs/ml. In some embodiments, the N. eutropha
is administered as two 15 ml doses per day, where each dose is at a
concentration of 10.sup.9 CFU/ml.
[0478] In some embodiments, ammonia oxidizing bacteria, e.g., the
N. eutropha is administered once, twice, three, or four times per
day. In some embodiments, ammonia oxidizing bacteria, e.g., the N.
eutropha is administered once, twice, three, four, five, or six
times per week. In some embodiments, ammonia oxidizing bacteria,
e.g., the N. eutropha is administered shortly after bathing. In
some embodiments, ammonia oxidizing bacteria, e.g., the N. eutropha
is administered shortly before sleep.
[0479] In certain aspects, the present disclosure provides
combination therapies comprising ammonia oxidizing bacteria, e.g.,
a N. eutropha and a second therapeutic. For instance, the
disclosure provides physical admixtures of the two (or more)
therapies are physically admixed. In other embodiments, the two (or
more) therapies are administered in combination as separate
formulation. The second therapy may be, e.g., a pharmaceutical
agent, surgery, or any other medical approach that treats the
relevant disease or disorder. The following paragraphs describe
combination therapies capable of treating diabetic ulcers, chronic
wounds, acne, rosacea, eczema, and psoriasis.
[0480] For instance, in a combination therapy capable of treating
diabetic ulcers, the second therapy may comprise, e.g., a wound
dressing (e.g., absorptive fillers, hydrogel dressings, or
hydrocolloids), angiotensin, angiotensin analogues, platelet-rich
fibrin therapy, hyperbaric oxygen therapy, negative pressure wound
therapy, debridement, drainage, arterial revascularization,
hyperbaric oxygen therapy, low level laser therapy, and
gastrocnemius recession. The combination therapy may comprise one
or more of the above-mentioned treatments.
[0481] In a combination therapy capable of treating chronic wounds,
the second therapy may comprise, e.g., an antibiotic (e.g., topical
or systemic, and bacteriocidal or bacteriostatic) such as
Penicillins, cephalosporins, polymyxins, rifamycins, lipiarmycins,
quinolones, sulfonamides, macrolides, lincosamides, tetracyclines,
cyclic lipopeptides, glycylcyclines, oxazolidinones, and
lipiarmycins; angiotensin, angiotensin analogues; debridement;
drainage; wound irrigation; negative pressure wound therapy;
application of heat; arterial revascularization; hyperbaric oxygen
therapy; antioxidants such as ascorbic acid, glutathione, lipoic
acid, carotenes, .alpha.-tocopherol, or ubiquinol; low level laser
therapy; gastrocnemius recession; growth factors such as vascular
endothelial growth factor, insulin-like growth factor 1-2, platelet
derived growth factor, transforming growth factor-.beta., or
epidermal growth factor; application of autologous platelets such
as those that secrete one or more growth factors such as vascular
endothelial growth factor, insulin-like growth factor 1-2, platelet
derived growth factor, transforming growth factor-.beta., or
epidermal growth factor; implantation of cultured keratinocytes;
allograft; collagen, for instance a dressing comprising collagen;
or protease inhibitors such as SLPI. The combination therapy may
comprise one or more of the above-mentioned treatments.
[0482] In a combination therapy capable of treating acne, the
second therapy may comprise, e.g., a medication (e.g., systemic or
topical) such as Benzoyl peroxide, antibiotics (such as
erythromycin, clindamycin, or a tetracycline), Salicylic acid,
hormones (e.g., comprising a progestin such as desogestrel,
norgestimate or drospirenone), retinoids such as tretinoin,
adapalene, tazarotene, or isotretinoin. The second therapy may also
be a procedure such as comedo extraction, corticosteroid injection,
or surgical lancing. The combination therapy may comprise one or
more of the above-mentioned treatments.
[0483] In a combination therapy capable of treating rosacea, the
second therapy may comprise, e.g., an antibiotic, e.g., an oral
tetracycline antibiotic such as tetracycline, doxycycline, or
minocycline, or a topical antibiotic such as metronidazole; azelaic
acid; alpha-hydroxy acid; isotretinoin can be prescribed;
sandalwood oil; clonidine; beta-blockers such as nadolol and
propranolol; antihistamines (such as loratadine); mirtazapine;
methylsulfonylmethane or silymarin, optionally in combination with
each other; lasers such as dermatological vascular laser or
CO.sub.2 laser; or light therapies such as intense pulsed light,
low-level light therapy or photorejuvenation. The combination
therapy may comprise one or more of the above-mentioned
treatments.
[0484] In a combination therapy capable of treating eczema, the
second therapy may comprise, e.g., a corticosteroid such as
hydrocortisone or clobetasol propionate, immunosuppressants
(topical or systemic) such as pimecrolimus, tacrolimus,
ciclosporin, azathioprine or methotrexate, or light therapy such as
with ultraviolet light. The combination therapy may comprise one or
more of the above-mentioned treatments.
[0485] In a combination therapy capable of treating psoriasis, the
second therapy may comprise, e.g., a corticosteroid such as
desoximetasone; a retinoid; coal tar; Vitamin D or an analogue
thereof such as paricalcitol or calcipotriol; moisturizers and
emollients such as mineral oil, vaseline, calcipotriol, decubal, or
coconut oil; dithranol; or fluocinonide. The combination therapy
may comprise one or more of the above-mentioned treatments.
[0486] While not wishing to be bound by theory, it is proposed that
treatment of psoriasis with a therapeutically effective dose of
ammonia oxidizing bacteria described herein may involve
downregulation of inflammation due to NO generation and reduction
in formation of human cathelicidin peptide LL-37.
[0487] While not wishing to be bound by theory, it is proposed that
treatment of psoriasis with a therapeutically effective dose of
ammonia oxidizing bacteria as described herein may involve
downregulation of inflammation due to NO generation.
[0488] While not wishing to be bound by theory, it is proposed that
treatment of impetigo or other skin and soft tissue infections with
a therapeutically effective dose of ammonia oxidizing bacteria as
described herein may involve limiting and/or inhibiting the spread
and proliferation of Staphylococcus aureus (S. aureus), e.g.,
methicillin resistant Staphylococcus aureus, Pseudomonas aeruginosa
(P. aeruginosa), Streptococcus pyogenes (S. pyogenes),
Acinetobacter baumannii (A. baumannii), Propionibacteria, and
Stenotrophomonas.
[0489] The present disclosure also provides a method of promoting
wound healing, comprising administering to a wound an effective
dose of ammonia oxidizing bacteria as described herein. Similarly,
the present disclosure provides ammonia oxidizing bacteria as
described herein for use in treating a wound. Likewise, the present
disclosure provides a use of ammonia oxidizing bacteria as
described herein in the manufacture of a medicament or a
composition for treating a wound.
[0490] Ammonia oxidizing bacteria as described herein may be used
to promote wound healing in a patient that has an impaired healing
ability, e.g., a diabetic patient.
[0491] In some embodiments, this disclosure provides methods of
using ammonia oxidizing bacteria as described herein to prevent a
disease or disorder, e.g., a skin disorder. Prevention, in certain
embodiments, means reducing the risk of a subject developing a
disease, compared to a similar untreated subject. The risk need not
be reduced to zero.
[0492] Individuals having a reduced bathing frequency, such as
astronauts, submarine crew members, military personnel during a
campaign, civilian workers in remote locations, refugees, bedridden
individuals and many others may maintain healthier skin by
maintaining ammonia oxidizing bacteria on the skin. With regard to
bedridden individuals, the ammonia oxidizing bacteria in some
embodiments reduces the frequency or severity of bed sores by
augmenting inadequate circulation.
[0493] It is appreciated that many modern degenerative diseases may
be caused by a lack of NO species, and that ammonia oxidizing
bacteria on the external skin can supply those species by
diffusion, and that application of ammonia oxidizing bacteria to
the skin resolves long standing medical conditions. In certain
embodiments, ammonia oxidizing bacteria are applied to a subject to
offset modern bathing practices, especially with anionic detergents
remove ammonia oxidizing bacteria from the external skin.
[0494] One suitable method of topical application to apply
sufficient ammonia oxidizing bacteria and then wear sufficient
clothing so as to induce sweating. However, many people will want
to derive the benefits of ammonia oxidizing bacteria while
maintaining their current bathing habits, in which case, a culture
of the bacteria can be applied along with sufficient substrate for
them to produce NO. A nutrient solution approximating the inorganic
composition of human sweat can be used for this purpose. Using
bacteria adapted to media approximating human sweat minimizes the
time for them to adapt when applied. Since sweat evaporates once
excreted onto the skin surface, using a culture media that has a
higher ionic strength is desirable. A concentration approximately
twice that of human sweat is suitable, but other conditions are
also contemplated. Ammonia oxidizing bacteria's nutritional needs
are typically met with NH.sub.3 or urea, O.sub.2, CO.sub.2, and
minerals. In some embodiments, the substrate comprises trace
minerals including iron, copper, zinc, cobalt, molybdenum,
manganese, sodium, potassium, calcium, magnesium, chloride,
phosphate, sulfate, or any combination thereof.
[0495] In some embodiments, the present disclosure provides a
method of treating a wound by applying a bandage comprising ammonia
oxidizing bacteria to the wound. Also provided are methods of
producing such a bandage. The bandage may comprise, for example, an
adhesive portion to affix the bandage to undamaged skin near the
wound and a soft, flexible portion to cover or overlay the wound.
In some embodiments, the bandage contains no other organisms but
ammonia oxidizing bacteria. The bandage may made of a permeable
material that allows gasses like oxygen and carbon dioxide to reach
the ammonia oxidizing bacteria when the bandage is applied to the
wound. In certain embodiments, the bandage comprises nutrients for
ammonia oxidizing bacteria such as ammonium, ammonia, urea, or
trace minerals. In certain embodiments, the bandage comprises an
antibiotic to which the ammonia oxidizing bacteria is resistant.
The antibiotic resistance may arise from one or more endogenous
resistance gene or from one or more transgenes.
[0496] In some embodiments, the ammonia oxidizing bacteria, e.g., a
preparation of ammonia oxidizing bacteria, is administered at a
dose of about 10.sup.8-10.sup.9 CFU, 10.sup.9-10.sup.10 CFU,
10.sup.10-10.sup.11 CFU, or 10.sup.11-10.sup.12 CFU per application
or per day. In some embodiments, the ammonia oxidizing bacteria is
administered topically at a dose of about 10.sup.9-10.sup.10 CFU,
e.g., about 1.times.10.sup.9-5.times.10.sup.9,
1.times.10.sup.9-3.times.10.sup.9, or
1.times.10.sup.9-10.times.10.sup.9 CFU.
[0497] In some embodiments, the ammonia oxidizing bacteria is
administered in a volume of about 1-2, 2-5, 5-10, 10-15, 12-18,
15-20, 20-25, or 25-50 ml per dose. In some embodiments, the
solution is at a concentration of about 10.sup.8-10.sup.9,
10.sup.9-10.sup.10, or 10.sup.10-10.sup.11 CFU/ml. In some
embodiments, the ammonia oxidizing bacteria is administered as two
15 ml doses per day, where each dose is at a concentration of
10.sup.9 CFU/ml.
[0498] In some embodiments, the ammonia oxidizing bacteria is
administered once, twice, three, or four times per day. In some
embodiments, the ammonia oxidizing bacteria is administered once,
twice, three, four, five, or six times per week. In some
embodiments, the ammonia oxidizing bacteria is administered shortly
after bathing. In some embodiments, the ammonia oxidizing bacteria
is administered shortly before sleep.
[0499] In some embodiments, the ammonia oxidizing bacteria is
administered for about 1-3, 3-5, 5-7, 7-9, 5-10, 10-14, 12-18,
12-21, 21-28, 28-35, 35-42, 42-49, 49-56, 46-63, 63-70, 70-77,
77-84, 84-91 days, e.g., for about 1 month, for about 2 months, for
about 3 months. In some embodiments, the ammonia oxidizing bacteria
is administered for an indefinite period of time, e.g., greater
than one year, greater than 5 years, greater than 10 years, greater
than 15 years, greater than 30 years, greater than 50 years,
greater than 75 years.
6. EXPERIMENTAL MODELS FOR REFINING D23 TREATMENTS
[0500] Treatments comprising ammonia oxidizing bacteria as
described herein (optionally in combination with another therapy)
can be refined using a number of model systems. These model systems
can be used to determine suitable doses and timing of
administration.
[0501] For instance, with respect to chronic wounds and diabetic
ulcers, one may use the mouse skin puncture model. Other models for
these disorders include controlled cutaneous ischemia in a guinea
pig model, rabbit ear ulcer model, application of calcium to a
wound, or topical application of doxorubicin.
[0502] With respect to acne, one may use (for example) the Mexican
hairless dog model, the Rhino mouse model, or the rabbit ear assay.
With respect to rosacea, one may use (for example) intradermal
injection of LL-37 into mouse skin or the Syrian hamster model.
With respect to eczema, one may use (for example) application of a
crude extract of Dermatophagoides farina, application of
dinitrochlorobenzene to the ears of sensitized guinea pigs, or
NC/Nga mice. With respect to psoriasis, one may use (for example)
xenograft models in which involved and uninvolved psoriatic skin
are transplanted onto immunodeficient mice, application of an
antibody directed against interleukin 15 to the skin of SCID mice,
and the Sharpin.sup.cpdm/Sharpin.sup.cpdm mouse model.
[0503] Treatments comprising ammonia oxidizing bacteria, e.g., N.
eutropha as described herein (e.g., strain D23) (optionally in
combination with another therapy) can be refined using a number of
model systems. These model systems can be used to determine
suitable doses and timing of administration.
[0504] For instance, with respect to chronic wounds and diabetic
ulcers, one may use the mouse skin puncture model described herein
in Example 6. Other models for these disorders include controlled
cutaneous ischemia in a guinea pig model, rabbit ear ulcer model,
application of calcium to a wound, or topical application of
doxorubicin.
[0505] With respect to acne, one may use (for example) the Mexican
Hairless Dog model, the Rhino mouse model, or the rabbit ear assay.
With respect to rosacea, one may use (for example) intradermal
injection of LL-37 into mouse skin or the Syrian hamster model.
With respect to eczema, one may use (for example) application of a
crude extract of Dermatophagoides farina, application of
dinitrochlorobenzene to the ears of sensitized guinea pigs, or
NC/Nga mice. With respect to psoriasis, one may use (for example)
xenograft models in which involved and uninvolved psoriatic skin
are transplanted onto immunodeficient mice, application of an
antibody directed against interleukin 15 to the skin of SCID mice,
and the Sharpin.sup.cpdm/Sharpin.sup.cpdm mouse model.
7. MECHANISM OF THERAPEUTIC BENEFIT
[0506] While not wishing to be bound by theory, it is believed that
one or more of the following mechanisms contributes to the
beneficial effect of ammonia oxidizing bacteria, e.g., N. eutropha
in treating the diseases and conditions discussed herein.
Additional mechanistic details are found in International
Application WO/2005/030147, which is herein incorporated by
reference in its entirety.
[0507] In order to understand the beneficial aspects of these
bacteria, it is helpful to understand angiogenesis. All body cells,
except those within a few hundred microns of the external air,
receive all metabolic oxygen from the blood supply. The oxygen is
absorbed by the blood in the lung, is carried by red blood cells as
oxygenated hemoglobin to the peripheral tissues, where it is
exchanged for carbon dioxide, which is carried back and exhaled
from the lung. Oxygen must diffuse from the erythrocyte, through
the plasma, through the endothelium and through the various tissues
until it reached the mitochondria in the cell which consumes it.
The human body contains about 5 liters of blood, so the volume of
the circulatory system is small compared to that of the body.
Oxygen is not actively transported. It passively diffuses down a
concentration gradient from the air to the erythrocyte, from the
erythrocyte to the cell, and from the cell to cytochrome oxidase
where it is consumed. The concentration of oxygen at the site of
consumption is the lowest in the body, and the O.sub.2 flux is
determined by the diffusion resistance and the concentration
gradient. Achieving sufficient oxygen supply to all the peripheral
tissues requires exquisite control of capillary size and location.
If the spacing between capillaries were increased, achieving the
same flux of oxygen would require a larger concentration difference
and hence a lower O.sub.2 concentration at cytochrome oxidase. With
more cells between capillaries, the O.sub.2 demand would be
greater. If the spacing between capillaries were decreased, there
would be less space available for the cells that perform the
metabolic function of the organ.
[0508] In certain aspects, it is appreciated that NO from ammonia
oxidizing bacteria is readily absorbed by the outer skin and
converted into S-nitrosothiols since the outer skin is free from
hemoglobin. M. Stucker et al. have shown that the external skin
receives all of its oxygen from the external air in "The cutaneous
uptake of atmospheric oxygen contributes significantly to the
oxygen supply of human dermis and epidermis. (Journal of Physiology
(2002), 538.3, pp. 985-994.) This is readily apparent, because the
external skin can be seen to be essentially erythrocyte free. There
is circulation of plasma through these layers because they are
living and do require the other nutrients in blood, just not the
oxygen. S-nitrosothiols formed are stable, can diffuse throughout
the body, and constitute a volume source of authentic NO and a
source of NO to transnitrosate protein thiols.
[0509] In some aspects, it is appreciated that capillary
rarefaction may be one of the first indications of insufficient
levels of NO. F. T. Tarek et al. have shown that sparse
capillaries, or capillary rarefaction, is commonly seen in people
with essential hypertension. (Structural Skin Capillary Rarefaction
in Essential Hypertension. Hypertension. 1999; 33:998-1001
[0510] A great many conditions are associated with the capillary
density becoming sparser. Hypertension is one, and researchers
reported that sparse capillaries are also seen in the children of
people with essential hypertension, and also in people with
diabetes. Significant complications of diabetes are hypertension,
diabetic nephropathy, diabetic retinopathy, and diabetic
neuropathy. R. Candido et al. have found that the last two
conditions are characterized by a reduction in blood flow to the
affected areas prior to observed symptoms. (Haemodynamics in
microvascular complications in type 1 diabetes. Diabetes Metab Res
Rev 2002; 18: 286-304.) Reduced capillary density is associated
with obesity, and simple weight loss increases capillary density as
shown by A Philip et al. in "Effect of Weight Loss on Muscle Fiber
Type, Fiber Size, Capilarity, and Succinate Dehydrogenase Activity
in Humans. The Journal of Clinical Endocrinology & Metabolism
Vol. 84, No. 11 4185-4190, 1999.
[0511] Researchers have shown that in primary Raynaud's phenomena
(PRP), the nailfold capillaries are sparser (slightly) than in
normal controls, and more abundant than in patients that have
progressed to systemic sclerosis (SSc). M. Bukhari, Increased
Nailfold Capillary Dimensions In Primary Raynaud's Phenomenon And
Systemic Sclerosis. British Journal of Rheumatology, Vol. 24 No 35:
1127-1131, 1996. They found that the capillary density decreased
from 35 loops/mm.sup.2 (normal controls) to 33 (PRP), to 17 (SSc).
The average distance between capillary limbs was 18.mu., 18.mu.,
and 30.mu. for controls, PRP and SSc, respectively.
[0512] In certain aspects, it is appreciated that the mechanism
that the body normally uses to sense "hypoxia" may affect the
body's system that regulates capillary density. According to this
aspect of the invention, a significant component of "hypoxia" is
sensed, not by a decrease in O2 levels, but rather by an increase
in NO levels. Lowering of basal NO levels interferes with this
"hypoxia" sensing, and so affects many bodily functions regulated
through "hypoxia." For Example, anemia is commonly defined as "not
enough hemoglobin," and one consequence of not enough hemoglobin is
"hypoxia", which is defined as "not enough oxygen." According to
some aspects, these common definitions do not account for the
nitric oxide mediated aspects of both conditions.
[0513] At rest, acute isovolemic anemia is well tolerated. A 2/3
reduction in hematocrit has minimal effect on venous return PvO2,
indicating no reduction in either O.sub.2 tension or delivery
throughout the entire body. Weiskopf et al. Human cardiovascular
and metabolic response to acute, severe isovolemic anemia. JAMA
1998, vol 279, No. 3, 217-221. At 50% reduction (from 140 to 70 g
Hb/L), the average PvO2 (over 32 subjects) declined from about 77%
to about 74% (of saturation). The reduction in O.sub.2 capacity of
the blood is compensated for by vasodilatation and tachycardia with
the heart rate increasing from 63 to 85 bpm. That the compensation
is effective is readily apparent, however, the mechanism is not. A
typical explanation is that "hypoxia" sensors detected "hypoxia"
and compensated with vasodilatation and tachycardia. However, there
was no "hypoxia" to detect. There was a slight decrease in blood
lactate (a marker for anaerobic respiration) from 0.77 to 0.62 mM/L
indicating less anaerobic respiration and less "hypoxia." The 3%
reduction in venous return PvO2 is the same level of "hypoxia" one
would get by ascending 300 meters in altitude (which typically does
not produce tachycardia). With the O.sub.2 concentration in the
venous return staying the same, and the O.sub.2 consumption staying
the same, there is no place in the body where there is a reduction
in O.sub.2 concentration. Compensation during isovolemic anemia may
not occur because of O.sub.2 sensing.
[0514] Thus the vasodilatation that is observed in acute isovolemic
anemia may be due to the increased NO concentration at the vessel
wall. NO mediates dilatation of vessels in response to shear stress
and other factors. No change in levels of NO metabolites would be
observed, because the production rate of NO is unchanged and
continues to equal the destruction rate. The observation of no
"hypoxic" compensation with metHb substitution can be understood
because metHb binds NO just as Hb does, so there is no NO
concentration increase with metHb substitution as there is with Hb
withdrawal.
[0515] Nitric oxide plays a role in many metabolic pathways. It has
been suggested that a basal level of NO exerts a tonal inhibitory
response, and that reduction of this basal level leads to a
dis-inhibition of those pathways. Zanzinger et al. have reported
that NO has been shown to inhibit basal sympathetic tone and
attenuate excitatory reflexes. (Inhibition of basal and
reflex-mediated sympathetic activity in the RVLM by nitric oxide.
Am. J. Physiol. 268 (Regulatory Integrative Comp. Physiol. 37):
R958-R962, 1995.)
[0516] In some aspects, it is appreciated that one component of a
volume source of NO is low molecular weight S-nitrosothiols
produced in the erythrocyte free skin from NO produced on the
external skin by ammonia oxidizing bacteria. These low molecular
weight S-nitrosothiols are stable for long periods, and can diffuse
and circulate freely in the plasma. Various enzymes can cleave the
NO from various S-nitrosothiols liberating NO at the enzyme site.
It is the loss of this volume source of NO from AOB on the skin
that leads to disruptions in normal physiology. The advantage to
the body of using S-nitrosothiols to generate NO far from a
capillary is that O.sub.2 is not required for NO production from
S-nitrosothiols. Production of NO from nitric oxide synthase (NOS)
does require O.sub.2. With a sufficient background of
S-nitrosothiols, NO can be generated even in anoxic regions. Free
NO is not needed either since NO only exerts effects when attached
to another molecule, such as the thiol of a cysteine residue or the
iron in a heme, so the effects of NO can be mediated by
transnitrosation reactions even in the absence of free NO provided
that S-nitrosothiols and transnitrosation enzymes are present.
[0517] Frank et al. have shown that the angiogenesis that
accompanies normal wound healing is produced in part by elevated
VEGF which is induced by increased nitric oxide. (Nitric oxide
triggers enhanced induction of vascular endothelial growth factor
expression in cultured keratinocytes (HaCaT) and during cutaneous
wound repair. FASEB J. 13, 2002-2014 (1999).)
[0518] NO has a role in the development of cancer, indicating that
the bacteria described herein may be used in methods of cancer
treatment and prevention. According to certain aspects, it is
appreciated that the presence of NO during hypoxia may prevent
cells from dividing while under hypoxic stress, when cells are at
greater risk for errors in copying DNA. One relevant cell function
is the regulation of the cell cycle. This is the regulatory program
which controls how and when the cell replicates DNA, assembles it
into duplicate chromosomes, and divides. The regulation of the cell
cycle is extremely complex, and is not fully understood. However,
it is known that there are many points along the path of the cell
cycle where the cycle can be arrested and division halted until
conditions for doing so have improved. The p53 tumor suppressor
protein is a key protein in the regulation of the cell cycle, and
it serves to initiate both cell arrest and apoptosis from diverse
cell stress signals including DNA damage and p53 is mutated in over
half of human cancers as reported by Ashcroft et al. in "Stress
Signals Utilize Multiple Pathways To Stabilize p53." (Molecular And
Cellular Biology, May 2000, p. 3224-3233.) Hypoxia does initiate
accumulation of p53, and while hypoxia is important in regulating
the cell cycle, hypoxia alone fails to induce the downstream
expression of p53 mRNA effector proteins and so fails to cause
arrest of the cell cycle. Goda et al. have reported that hypoxic
induction of cell arrest requires hypoxia-inducing factor-1
(HIF-1.alpha.). (Hypoxia-Inducible Factor 1.alpha. Is Essential for
Cell Cycle Arrest during Hypoxia. Molecular And Cellular Biology,
January 2003, p. 359-369.) Britta et al. have reported that NO is
one of the main stimuli for HIF-1.alpha.. (Accumulation of
HIF-1.alpha. under the influence of nitric oxide. Blood, 15 Feb.
2001, Volume 97, Number 4.) In contrast, NO does cause the
accumulation of transcriptionally active p53 and does cause arrest
of the cell cycle and does cause apoptosis. Wang et al., P53
Activation By Nitric Oxide Involves Down-Regulation Of Mdm2. THE
JOURNAL OF BIOLOGICAL CHEMISTRY Vol. 277, No. 18, Issue Of May 3,
Pp. 15697-15702, 2002.
[0519] In certain aspect of the invention, it is appreciated that
preventing the necrotic death of cells by preventing the capillary
rarefaction that leads to their hypoxic death may prevent
autoimmune disorders. When cells are exposed to chronic hypoxia,
the production of reactive oxygen species (ROS) is increased, and
there is increased damage to the cells metabolic machinery and
ultimately to the cells' DNA. Decreased metabolic capacity will
decrease capacity for repair of damage due to ROS and due to
exogenous carcinogen exposure. Over time, the damage accumulates
and increases the chance of three events: the cell will undergo
deletion of cancer-preventing genes and the cell will become
cancerous, the cell will die through necrosis, or the cell will die
through apoptosis. When cells die, either through necrosis or
apoptosis, the cell debris must be cleared from the site. Dead
cells are phagocytosed by immune cells, including dendritic cells
and macrophages. When these cells phagocytose a body, it is
digested by various proteolytic enzymes into antigenic fragments,
and then these antigens are attached to the major
histocompatibility complex (MHC1, MHC2) and the antigen-MHC complex
is moved to the surface of the cell where it can interact with T
cells and activate the T cells in various ways. Any cell injury
releases adjuvants which stimulate the immune system in various
ways. In general, cells that undergo necrosis stimulate a greater
immune response than cells that undergo apoptosis. Chronic exposure
of immune cells to dead and dying cells is therefore likely to lead
to autoimmune disorders.
[0520] In certain aspects, it is appreciated that low basal NO
leads to fibrotic hypertrophy. Once a dead cell has been cleared, a
new cell cannot easily take its place, because there is
insufficient O.sub.2 to support it. Any such new cell would suffer
the same fate. The space can remain empty, in which case the organ
shrinks, the capillaries draw closer together, new cells are now
deprived of the VEGF formerly produced by the now-missing cell, so
capillaries ablate and the hypoxic zone reforms. This could result
in a general shrinkage of the affected tissues. In tissues that
support fibrosis, relatively inert collagen fibers can fill the
space. Since the metabolic requirements of the body for the
particular organ in question are not reduced, the organ may attempt
to grow larger, but now with a significant fibrous content. This
may result in fibrotic hypertrophy, such as of the heart and liver.
Some organs, such as the brain, cannot grow larger or smaller
because the three-dimensional connectivity of nerves and blood
vessels are important, and cannot be continuously and
simultaneously mapped onto an asymmetrically shrinking brain. The
space must be filled with something, and .beta.-amyloid might be
the (not so inert) space filler. The kidney cannot grow larger
because of the renal capsule, so the number of living cells becomes
smaller and they are replaced with fibrotic tissue. If the dead
cells are cleared, the tissue shrinks, and the ratio of NO/O.sub.2
goes down again, and the capillaries again become sparser. This may
set up the vicious circle of end stage renal disease, congestive
heart failure/cardiac hypertrophy, primary biliary cirrhosis,
Alzheimer's disease, atherosclerosis, inflammatory bowel disease,
hypertrophic scar formation, and the multiple connective tissue
diseases starting with Raynaud's phenomena and ending with Systemic
Sclerosis and primary Sjogren's syndrome where capillary
rarefaction is also observed. Ferrini et al, have shown that a
reduction in basal NO levels through chronic inhibition of NOS with
L-NAME leads to generalized fibrosis of the heart and kidneys.
(Antifibrotic Role of Inducible Nitric Oxide Synthase. Nitric
Oxide: Biology and Chemistry Vol. 6, No. 3, pp. 283-294 (2002).) It
may be that low basal NO leads to fibrotic hypertrophy.
[0521] In certain aspects, it is appreciated that capillary
rarefaction affects a subject's ability to control their appetite.
Capillary rarefaction is observed in the brains of aged humans and
animals. Capillary rarefaction is associated with declines in
circulating growth factors including insulin like growth factor-1.
Neurogenesis in the adult brain is coordinated with angiogenesis.
Since the brain regulates many homeostatic functions, increased
diffusion lengths between capillaries to control elements of the
brain might be "interpreted" as inadequate blood concentrations of
those species. The flux of glucose in the brain is quite close to
normal metabolic needs, where glucose flux is only 50 to 75%
greater than glucose consumption and the glucose transporters
across the blood brain barrier are saturable, stereospecific and
independent of energy or ion gradients. A large part of the
regulation of appetite is mediated through the brain, and capillary
rarefaction may cause an adequate blood concentration of
"nutrients" (or marker compounds proportional to "nutrients") to be
interpreted as insufficient. This may be one cause of obesity.
[0522] According to certain aspects, it is appreciated that
capillary rarefaction may be a cause of non-insulin dependent
diabetes. Non-insulin dependent diabetes (NIDDM) is also known as
the Metabolic Syndrome or Diabetes type 2, and is characterized by
insulin resistance. The sensitivity of the body to insulin is
reduced, and insulin levels increase People with NIDDM have high
blood glucose, high blood triglycerides, are typically obese,
hypertensive, and typically have significant visceral fat.
[0523] Other symptoms accompany NIDDM, which may point to capillary
rarefaction as the cause. In a study of 40 men, with and without
NIDDM, obese (BMI 29) and lean (BMI 24) (10 of each), Konrad et al.
report that blood lactate levels at rest were 1.78, 2.26, 2.42, and
2.76 (mM/L) for lean men without, obese men without, lean men with
NIDDM, obese men with NIDDM respectively. (A-Lipoic acid treatment
decreases serum lactate and pyruvate concentrations and improves
glucose effectiveness in lean and obese patients with type 2
diabetes. Diabetes Care 22:280-287, 1999.) Lactate is a measure of
anaerobic glycolysis. When O.sub.2 is insufficient to generate ATP
through oxidative phosphorylation, cells can produce ATP through
anaerobic glycolysis. One of the products of anaerobic glycolysis
is lactate, which must be exported from the cells, otherwise the pH
drops and function is compromised. Blood lactate is commonly
measured in exercise studies, where an increase indicates the work
load at which maximum oxidative work can be done. Higher levels of
lactate at rest would indicate increased anaerobic glycolysis at
rest, which is consistent with capillary rarefaction.
[0524] Primary biliary cirrhosis is associated with Raynaud's
phenomena, pruritus, sicca syndrome, osteoporosis, portal
hypertension, neuropathy, and pancreatic insufficiency, and liver
abnormalities are associated with rheumatic diseases. Elevated
liver enzymes are a symptom of liver inflammation, and elevated
liver enzymes are observed as an early symptom of "asymptomatic"
primary biliary cirrhosis. Accordingly, the bacteria described
herein may be used to treat liver inflammation.
[0525] Torre et al have reported that Alzheimer's disease (AD) is a
microvascular disorder with neurological degeneration secondary to
hypoperfusion, resulting in part from insufficient nitric oxide.
(Review: Evidence that Alzheimer's disease is a microvascular
disorder: the role of constitutive nitric oxide, Brain Research
Reviews 34 (2000) 119-136.) Accordingly, the bacteria described
herein may be used to treat AD.
[0526] Adverse health effects that are associated with hypertension
may also be consequences of low basal NO. The decreased response to
vasodilatation is also consistent with low basal NO. NO is a
diffusible molecule that diffuses from a source to a sensor site
where it has the signaling effect. With low NO levels, every NO
source must produce more NO to generate an equivalent NO signal of
a certain intensity a certain distance away. NO diffuses in three
dimensions and the whole volume within that diffusion range must be
raised to the level that will give the proper signal at the sensor
location. This may result in higher NO levels at the source and
between the source and the sensor. Adverse local effects of
elevated NO near a source may then arise from too low a NO
background. There is some evidence that this scenario actual
occurs. In rat pancreatic islets, Henningsson et al have reported
that inhibition of NOS with L-NAME increases total NO production
through the induction of iNOS. (Chronic blockade of NO synthase
paradoxically increases islet NO production and modulates islet
hormone release. Am J Physiol Endocrinol Metab 279: E95-E107,
2000.) Increasing NO by increasing NOS activity will only work up
to some limit. When NOS is activated but is not supplied with
sufficient tetrahydrobiopterin (BH4) or L-arginine, it becomes
"uncoupled" and generates superoxide (O2-) instead of NO. This
O.sub.2.sup.- may then destroy NO. Attempting to produce NO at a
rate that exceeds the supply of BH4 or L-arginine may instead
decrease NO levels. This may result in positive feedback where low
NO levels are made worse by stimulation of NOS, and uncoupled NOS
generates significant O.sub.2.sup.- which causes local reactive
oxygen species (ROS) damage such as is observed in atherosclerosis,
end stage renal disease, Alzheimer's, and diabetes.
[0527] The bacteria described herein may also be used to delay the
signs of aging. Caloric restriction extends lifespan, and Holloszy
reported that restricting food intake to 70% of ad lib controls,
prolongs life in sedentary rats from 858 to 1,051 days, almost 25%.
(Mortality rate and longevity of food restricted exercising male
rats: a reevaluation. J. Appl. Physiol. 82(2): 399-403, 1997.) The
link between calorie restriction and prolonged life is well
established, however, the causal mechanism is not. Lopez-Torres et
al. reported that the examination of liver mitochondrial enzymes in
rats indicates a reduction in H.sub.2O.sub.2 production due to
reduced complex I activity associated with calorie restriction.
(Influence Of Aging And Long-Term Caloric Restriction On Oxygen
Radical Generation And Oxidative DNA Damage In Rat Liver
Mitochondria. Free Radical Biology & Medicine Vol. 32 No 9 pp
882-8899, 2002.) H.sub.2O.sub.2 is produced by dismutation of
O.sub.2.sup.-, which is a major ROS produced by the mitochondria
during respiration. The main source of O.sub.2.sup.- has been
suggested by Kushareva et al. and others to be complex I which
catalyzes the NAD/NADH redox couple by reverse flow of electrons
from complex III, the site of succinate reduction. The free radical
theory, proposed by Beckman, of aging postulates, that free radical
damage to cellular DNA, antioxidant systems and DNA repair systems
accumulates with age and when critical systems are damaged beyond
repair, death ensues. (The Free Radical Theory of Aging Matures.
Physiol. Rev. 78: 547-581, 1998.)
[0528] As an additional mechanism, NO has been demonstrated by Vasa
et al. to activate telomerase and to delay senescence of
endothelial cells. (Nitric Oxide Activates Telomerase and Delays
Endothelial Cell Senescence. Circ Res. 2000; 87:540-542.) Low basal
NO will increase basal metabolic rate by disinhibition of
cytochrome oxidase. Increased basal metabolism will also increase
cell turn-over and growth rate. Capillary rarefaction, by inducing
chronic hypoxia may increase free radical damage and may also
increase cell turn-over, and so accelerate aging by both
mechanisms.
[0529] In some aspects, it is appreciated that autotrophic
ammonia-oxidizing bacteria may produce protective aspects for
allergies and autoimmune disorders. The best known autoimmune
disease is perhaps Diabetes Type 1, which results from the
destruction of the insulin producing cells in the pancreas by the
immune system. Recurrent pregnancy loss is also associated with
autoimmune disorders where the number of positive autoimmune
antibodies correlated positively with numbers recurrent pregnancy
losses. Systemic Sclerosis, Primary Biliary Cirrhosis, autoimmune
hepatitis, and the various rheumatic disorders are other examples
of autoimmune disorders. Application of AOB was observed to reduce
an allergy, hay fever, as described in WO/2005/030147.
[0530] One mechanism by which AOB may exert their protective effect
on allergies and autoimmune disorders is through the production of
nitric oxide, primarily through the regulatory inhibition of
NF-.kappa.B and the prevention of activation of immune cells and
the induction of inflammatory reactions. NF-.kappa.B is a
transcription factor that up-regulates gene expression and many of
these genes are associated with inflammation and the immune
response including genes which cause the release of cytokines,
chemokines, and various adhesion factors. These various immune
factors cause the migration of immune cells to the site of their
release resulting in the inflammation response. Constitutive NO
production has been shown to inhibit NF-.kappa.B by stabilizing
I.kappa.B.alpha. (an inhibitor of NF-.kappa.B) by preventing
I.kappa.B.alpha. degradation.
[0531] Administration of an NO donor has been shown by Xu et al. to
prevent the development of experimental allergic encephalomyelitis
in rats. (SIN-1, a Nitric Oxide Donor, Ameliorates Experimental
Allergic Encephalomyelitis in Lewis Rats in the Incipient Phase:
The Importance of the Time Window. The Journal of Immunology, 2001,
166: 5810-5816.) In this study, it was demonstrated that
administering an NO donor, reduced the infiltration of macrophages
into the central nervous system, reduced the proliferation of blood
mononuclear cells, and increased apoptosis of blood mononuclear
cells. All of these results are expected to reduce the extent and
severity of the induced autoimmune response.
[0532] Low basal NO may lead to autism via the mechanism that new
connections in the brain are insufficiently formed as a result of
insufficient basal nitric oxide. While not wishing to be bound in
theory, in some embodiments, formation of neural connections is
modulated by NO. In these cases, any condition that lowers the
range of NO diffusion may decrease the volume size of brain
elements that can undergo connections. A brain which developed
under conditions of low basal NO levels may be arranged in smaller
volume elements because the reduced effective range of NO.
[0533] Additional symptoms exhibited in autistic individuals may
also point to low NO as a cause, including increased pitch
discrimination, gut disturbances, immune system dysfunction,
reduced cerebral blood flow, increased glucose consumption of the
brain, increased plasma lactate, attachment disorders, and humming.
Each of these symptoms may be attributed to a low basal NO
level.
[0534] Takashi Ohnishi et al. have reported that autistic
individuals show decreased blood flow. Takashi Ohnishi et al.,
Abnormal regional cerebral blood flow in childhood autism. Brain
(2000), 123, 1838-1844. J. M. Rumsey et al. have reported that
autistic individuals have increased glucose consumption. Rumsey J
M, Duara R, Grady C, Rapoport J L, Margolin R A, Rapoport S I,
Cutler N R. Brain metabolism in autism. Resting cerebral glucose
utilization rates as measured with positron emission tomography.
Arch Gen Psychiatry, 1985 May; 42(5):448-55 (abstract). D. C.
Chugani has reported that autistic individuals have an increased
plasma lactate levels. Chugani D C, et al., Evidence of altered
energy metabolism in autistic children. Prog Neuropsychopharmacol
Biol Psychiatry. 1999 May; 23(4):635-41. The occurrence of these
effects may be a result of capillary rarefaction in the brain,
which may reduce blood flow and O.sub.2 supply, such that some of
the metabolic load of the brain may be produced through glycolysis
instead of oxidative phosphorylation.
[0535] Nitric oxide has been demonstrated by B. A. Klyachko et al.
to increase the excitability of neurons by increasing the after
hyperpolarization through cGMP modification of ion channels. Vitaly
A. Klyachko et al., cGMP-mediated facilitation in nerve terminals
by enhancement of the spike after hyperpolarization. Neuron, Vol.
31, 1015-1025, Sep. 27, 2001. C. Sandie et al. have shown that
inhibition of NOS reduces startle. Carmen Sandi et al., Decreased
spontaneous motor activity and startle response in nitric oxide
synthase inhibitor-treated rats. European journal of pharmacology
277 (1995) 89-97. Attention-Deficit Hyperactivity Disorder (ADHD)
has been modeled using the spontaneously hypertensive rat (SHR) and
the Naples high-excitability (NHE) rat. Both of these models have
been shown by Raffaele Aspide et al, to show increased attention
deficits during periods of acute NOS inhibition. Raffaele Aspide et
al., Non-selective attention and nitric oxide in putative animal
models of attention-deficit hyperactivity disorder. Behavioral
Brain Research 95 (1998) 123-133. Accordingly, the bacteria herein
may be used in the treatment of ADHD.
[0536] Inhibition of NOS has also been shown by M. R. Dzoljic to
inhibit sleep. M. R. Dzoljic, R. de Vries, R. van Leeuwen. Sleep
and nitric oxide: effects of 7-nitro indazole, inhibitor of brain
nitric oxide synthase. Brain Research 718 (1996) 145-150. G.
Zoccoli has reported that a number of the physiological effects
seen during sleep are altered when NOS is inhibited, including
rapid eye movement and sleep-wake differences in cerebral
circulation. G. Zoccoli, et al., Nitric oxide inhibition abolishes
sleep-wake differences in cerebral circulation. Am. J. Physiol.
Heart Circ Physiol 280: H2598-2606, 2001. NO donors have been shown
by L. Kapas et al. to promote non-REM sleep, however, these
increases persisted much longer than the persistence of the NO
donor, suggesting perhaps a rebound effect. Levente Kapas et al.
Nitric oxide donors SIN-1 and SNAP promote nonrapid-eye-movement
sleep in rats. Brain Research Bullitin, vol 41, No 5, pp. 293-298,
1996. M. Rosaria et al., Central NO facilitates both penile
erection and yawning. Maria Rosaria Melis and Antonio Argiolas.
Role of central nitric oxide in the control of penile erection and
yawning. Prog Neuro-Psychopharmacol & Biol. Phychiat. 1997, vol
21, pp 899-922. P. Tani et al, have reported that insomnia is a
frequent finding in adults with Asperger's. Pekka Tani et al.,
Insomnia is a frequent finding in adults with Asperger's syndrome.
BMC Psychiatry 2003, 3:12. Y. Hoshino has also observed sleep
disturbances in autistic children. Hoshino Y, Watanabe H, Yashima
Y, Kaneko M, Kumashiro H. An investigation on sleep disturbance of
autistic children. Folia Psychiatr Neurol Jpn. 1984; 38(1):45-51.
(abstract) K. A. Schreck et al. has observed that the severity of
sleep disturbances correlates with severity of autistic symptoms.
Schreck K A, et al., Sleep problems as possible predictors of
intensified symptoms of autism. Res Dev Disabil. 2004 Jan.-Feb.;
25(1):57-66. (abstract). Accordingly, the bacteria herein may be
used in the treatment of insomnia.
[0537] W. D. Ratnasooriya et al reported that inhibition of NOS in
male rats reduces pre-coital activity, reduces libido, and reduces
fertility. W. D. Ratnasooriya et al., Reduction in libido and
fertility of male rats by administration of the nitric oxide (NO)
synthase inhibitor N-nitro-L-arginine methyl ester. International
journal of andrology, 23: 187-191 (2000).
[0538] It may be that a number of seemingly disparate disorders,
characterized by ATP depletion and eventual organ failure are
actually "caused" by nitropenia, caused by a global deficiency in
basal nitric oxide. When this occurs in the heart, the result is
dilative cardiomyopathy. When this occurs in the brain, the result
is white matter hyperintensity, Alzheimer's, vascular depression,
vascular dementia, Parkinson's, and the Lewy body dementias. When
this occurs in the kidney, the result is end stage renal disease,
when this occurs in the liver, the result is primary biliary
cirrhosis. When this occurs in muscle, the consequence is
fibromyaligia, Gulf War Syndrome, or chronic fatigue syndrome. When
this occurs in the bowel, the consequence is ischemic bowel
disease. When this occurs in the pancreas, the consequence is first
type 2 diabetes, followed by chronic inflammation of the pancreas,
followed by autoimmune attack of the pancreas (or pancreatic
cancer), followed by type 1 diabetes. When this occurs in the
connective tissue, the consequence is systemic sclerosis.
[0539] In the remnant kidney model of end stage renal disease, part
of the kidney is removed, (either surgically or with a toxin) which
increases the metabolic load on the remainder. Superoxide is
generated to decrease NO and increase O.sub.2 diffusion to the
kidney mitochondria. Chronic overload results in progressive kidney
capillary rarefaction and progressive kidney failure. In acute
kidney failure, putting people in dialysis can give the kidney a
"rest", and allows it to recover. In acute renal failure induced by
rhabdomyolysis (muscle damage which releases myoglobin into the
blood stream) kidney damage is characterized by ischemic damage.
Myoglobin scavenges NO, just as hemoglobin does, and would cause
vasoconstriction in the kidney leading to ischemia. Myoglobin would
also induce local nitropenia and the cascade of events leading to
further ATP depletion.
[0540] In some aspects, low NO levels lead to reduced mitochondrial
biogenesis. Producing the same ATP at a reduced mitochondria
density will result in an increase in O.sub.2 consumption, or an
accelerated basal metabolic rate. An accelerated basal metabolic
rate is observed in a number of conditions, including: Sickle cell
anemia, Congestive heart failure, Diabetes, Liver Cirrhosis,
Crohn's disease, Amyotrophic lateral sclerosis, Obesity, End stage
renal disease, Alzheimer's, and chronic obstructive pulmonary
disease.
[0541] While some increased O.sub.2 consumption might be
productively used, in many of these conditions uncoupling protein
is also up-regulated, indicating that at least part of the
increased metabolic rate is due to inefficiency. Conditions where
uncoupling protein is known to be up-regulated include obesity and
diabetes.
[0542] With fewer mitochondria consuming O.sub.2 to a lower O.sub.2
concentration, the O.sub.2 gradient driving O.sub.2 diffusion is
greater, so the O.sub.2 diffusion path length can increase
resulting in capillary rarefaction, which is observed in dilative
cardiomyopathy, hypertension, diabetes type 2, and renal
hypertension.
[0543] Copper, either as Cu2+ or as ceruloplasmin (CP) (the main Cu
containing serum protein which is present at 0.38 g/L in adult sera
and which is 0.32% Cu and contains 94% of the serum copper)
catalyzes the formation of S--NO-thiols from NO and thiol
containing groups (RSH). The Cu content of plasma is variable and
is increased under conditions of infection. Berger et al. reported
that the Cu and Zn content of burn-wound exudates is considerable
with patients with 1/3 of their skin burned, losing 20 to 40% of
normal body Cu and 5 to 10% of Zn content in 7 days. (Cutaneous
copper and zinc losses in burns. Burns. 1992 October;
18(5):373-80.) If the patients skin were colonized by AOB, wound
exudates which contains urea and Fe, Cu, and Zn that AOB need,
would be converted into NO and nitrite, greatly supplementing the
local production of NO by iNOS, without consuming resources (such
as O.sub.2 and L-arginine) in the metabolically challenged wound. A
high production of NO and nitrite by AOB on the surface of a wound
would be expected to inhibit infection, especially by anaerobic
bacteria such as the Clostridia which cause tetanus, gas gangrene,
and botulism.
[0544] The practice of the present invention may employ, unless
otherwise indicated, conventional methods of immunology, molecular
biology, and recombinant DNA techniques within the skill of the
art. Such techniques are explained fully in the literature. See,
e.g., Sambrook, et al. Molecular Cloning: A Laboratory Manual
(Current Edition); and Current Protocols in Molecular Biology (F.
M. Ausubel, et al. eds., current edition).
8. NUCLEIC ACIDS AND PROTEINS FROM N. EUTROPHA
[0545] This disclosure provides, among other things, proteins and
nucleic acids (optionally, isolated proteins and nucleic acids)
that are identical to or similar to those found in strain D23.
While not wishing to be bound by theory, it is believed that the
sequenced strain of D23 has non-naturally occurring protein and
nucleic acid sequences due to an extended period of culture and
selection in the laboratory.
[0546] These nucleic acids and proteins have numerous uses. For
instance, the proteins may be used to generate antibodies or other
binding molecules that detect strain D23 or related strains. The
proteins may also be used to carry out reactions under
high-NH.sub.4.sup.+ conditions, because D23 is adapted for growth
and metabolism under these conditions. As another example, the
nucleic acids may be used to produce proteins for generating
antibodies or carrying out reactions as described above. The
nucleic acids may also be used to detect strain D23 or related
strains, e.g., using a microarray or another hybridization-based
assay.
[0547] The genome of strain D23 is provided as SEQ ID NO: 1. The
genome annotation (including the position and orientation of genes
within SEQ ID NO: 1) is provided as Supplementary Table 1.
Accordingly, this disclosure provides genes and proteins identical
or similar to the genes listed in Supplementary Table 1.
[0548] Accordingly, this disclosure provides a nucleic acid (e.g.,
an isolated nucleic acid) comprising a sequence of a gene of
Supplementary Table 1, as well as a protein encoded by said gene.
In certain embodiments, the nucleic acid comprises a sequence that
is similar (e.g., at least 70%, 80%, 85%, 90%, 95%, 97%, 98%, 99%,
or 99.5% identical) to a gene of Supplementary Table 1, or a
protein encoded by said gene. The disclosure also provides a
composition comprising a nucleic acid that is at least 1, 2, 3, 4,
5, 10, 15, 20, 50, 100, 200, 500, 1,000, 1,500, 2,000, 2,500, or
all of the sequences of Supplementary Table 1, or a sequence that
is similar thereto (e.g., at least 70%, 80%, 85%, 90%, 95%, 97%,
98%, 99%, or 99.5% identical), or one or more proteins encoded by
said nucleic acids. Also provided are fragments of said nucleic
acids and proteins.
[0549] The present disclosure also provides, inter alia, one or
more genes or proteins that are present in strain D23 and absent
from strain C91, or a gene or protein similar to one of said genes
or proteins. Examples of these genes are set out in FIGS. 6-8 and
are described in more detail in Example 4 herein. Examples of these
genes and proteins, as well as genes and proteins similar thereto,
are described below.
[0550] Accordingly, with respect to FIG. 6, this application
discloses nucleic acids that are identical or similar (e.g., at
least 70%, 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 99.5% identical)
to 1, 2, 3, 4, 5, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110,
120, 130, 140, 150, 160, or all of the sequences in FIG. 6. This
application also discloses proteins that are identical or similar
(e.g., at least 70%, 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 99.5%
identical) to 1, 2, 3, 4, 5, 10, 15, 20, 30, 40, 50, 60, 70, 80,
90, 100, 110, 120, 130, 140, 150, 160, or all of the proteins
encoded by the genes listed in FIG. 6. Furthermore, the application
discloses fragments of these genes and proteins, e.g., fragments of
0-20, 20-50, 50-100, 100-200, 200-500, 500-1000, or greater than
1000 nucleotides or amino acids. In some embodiments, a plurality
of the above-mentioned genes or proteins are affixed to a solid
support, e.g., to form a microarray.
[0551] With respect to FIG. 7, this application discloses nucleic
acids that are identical or similar (e.g., at least 70%, 80%, 85%,
90%, 95%, 97%, 98%, 99%, or 99.5% identical) to 1, 2, 3, 4, 5, 10,
15, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150,
160, or all of the sequences in FIG. 7. This application also
discloses proteins that are identical or similar (e.g., at least
70%, 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 99.5% identical) to 1,
2, 3, 4, 5, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120,
130, 140, 150, 160, or all of the proteins encoded by the genes
listed in FIG. 7. Furthermore, the application discloses fragments
of these genes and proteins, e.g., fragments of 0-20, 20-50,
50-100, 100-200, 200-500, 500-1000, or greater than 1000
nucleotides or amino acids. In some embodiments, a plurality of the
above-mentioned genes or proteins are affixed to a solid support,
e.g., to form a microarray.
[0552] With respect to FIG. 8, this application discloses nucleic
acids that are identical or similar (e.g., at least 70%, 80%, 85%,
90%, 95%, 97%, 98%, 99%, or 99.5% identical) to 1, 2, 3, 4, 5, 10,
15, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150,
200, or all of the sequences in FIG. 8. This application also
discloses proteins that are identical or similar (e.g., at least
70%, 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 99.5% identical) to 1,
2, 3, 4, 5, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120,
130, 140, 150, 200, or all of the proteins encoded by the genes
listed in FIG. 8. Furthermore, the application discloses fragments
of these genes and proteins, e.g., fragments of 0-20, 20-50,
50-100, 100-200, 200-500, 500-1000, or greater than 1000
nucleotides or amino acids. In some embodiments, a plurality of the
above-mentioned genes or proteins are affixed to a solid support,
e.g., to form a microarray.
[0553] With respect to FIGS. 6-8 collectively, this application
discloses nucleic acids that are identical or similar (e.g., at
least 70%, 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 99.5% identical)
to 1, 2, 3, 4, 5, 10, 20, 40, 60, 80, 100, 150, 200, 250, 300, 350,
400, 450, 500, or all of the sequences in FIGS. 6-8. This
application discloses proteins that are identical or similar (e.g.,
at least 70%, 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 99.5%
identical) to 1, 2, 3, 4, 5, 10, 20, 40, 60, 80, 100, 150, 200,
250, 300, 350, 400, 450, 500, or all of the proteins encoded by
genes listed in FIGS. 6-8. Furthermore, the application discloses
fragments of these genes and proteins, e.g., fragments of 1-20,
20-50, 50-100, 100-200, 200-500, 500-1000, or greater than 1000
nucleotides or amino acids. In some embodiments, a plurality of the
above-mentioned genes or proteins are affixed to a solid support,
e.g., to form a microarray.
[0554] This disclosure also provides nucleic acid sequences that
are fragments of SEQ ID NO: 1. The fragments may be, e.g., 1-20,
20-50, 50-100, 100-200, 200-500, 500-1000, 1,000-2,000,
2,000-5,000, or 10,000 or more nucleotides in length. The fragments
may also be at least about 80%, 85%, 90%, 95%, 97%, 98%, 99%, or
99.5% identity to the corresponding portion of SEQ ID NO: 1 or its
complement. The fragment may also be a fragment that hybridizes to
SEQ ID NO: 1, or to the genome of the D23 strain deposited with the
ATCC patent depository on Apr. 8, 2014, designated AOB D23-100 with
the ATCC under accession number PTA-121157, or their complements,
under low stringency, medium stringency, high stringency, or very
high stringency, or other hybridization condition described
herein.
[0555] The disclosure also provides nucleic acid sequences set out
in Table 1 (which describes genes involved in ammonia metabolism).
Accordingly, in some aspects, this application discloses genes that
are identical or similar (e.g., at least 70%, 80%, 85%, 90%, 95%,
96%, 97%, 97.5%, 98%, 98.2%, 98.4%, 98.6%, 98.8%, 99%, 99.1%,
99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100%
identical) to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or
all of the genes in Table 1. In embodiments, this application
discloses proteins that are identical or similar (e.g., at least
70%, 80%, 85%, 90%, 95%, 96%, 97%, 97.5%, 98%, 98.2%, 98.4%, 98.6%,
98.8%, 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%,
99.9%, or 100% identical) to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,
13, 14, 15, or all of the proteins in Table 1.
[0556] Alignment of the nucleic acid sequences of Table 1 shows the
percent identity between homologs in C91 and D23. The following
paragraphs discuss this percent identity and describe various
nucleic acids having homology to the D23 genes of Table 1.
[0557] More specifically, the amoA1 genes are about 98.8% identical
(i.e., at 821/831 positions). Accordingly, in some embodiments, the
amoA1 nucleic acid comprises D23 nucleotides at at least 1, 2, 3,
4, 5, 6, 7, 8, 9, 10, or all of the positions that differ in this
gene between strains C91 and D23. In embodiments, the amoA1 nucleic
acid comprise D23 nucleotides at at most 1, 2, 3, 4, 5, 6, 7, 8, 9,
10, or all of the positions that differ in this gene between
strains C91 and D23. In embodiments, the amoA1 nucleic acid
comprises a sequence at least about 98.8%, 98.9%, 99.0%, 99.2%,
99.4%, 99.6%, 99.8%, or 100% identical to the D23 amoA1 gene.
[0558] The amoA2 genes are about 98.8% identical (i.e., at 821/831
positions). Accordingly, in some embodiments, the amoA2 nucleic
acid comprises D23 nucleotides at at least 1, 2, 3, 4, 5, 6, 7, 8,
9, 10, or all of the positions that differ in this gene between
strains C91 and D23. In embodiments, the amoA2 nucleic acid
comprises D23 nucleotides at at most 1, 2, 3, 4, 5, 6, 7, 8, 9, 10,
or all of the positions that differ in this gene between strains
C91 and D23. In embodiments, the amoA2 nucleic acid comprises a
sequence at least about 98.8%, 98.9%, 99.0%, 99.2%, 99.4%, 99.6%,
99.8%, or 100% identical to the D23 amoA2 gene.
[0559] The amoB1 genes are about 99.1% identical (i.e., at
1255/1266 positions). Accordingly, in some embodiments, the amoB1
nucleic acid comprises D23 nucleotides at at least 1, 2, 3, 4, 5,
6, 7, 8, 9, 10, 11, or all of the positions that differ in this
gene between strains C91 and D23. In embodiments, the amoB1 nucleic
acid comprises D23 nucleotides at at most 1, 2, 3, 4, 5, 6, 7, 8,
9, 10, 11, or all of the positions that differ in this gene between
strains C91 and D23. In embodiments, the amoB1 nucleic acid
comprises a sequence at least about 99.1%, 99.2%, 99.4%, 99.6%,
99.8%, or 100% identical to the D23 amoB1 gene.
[0560] The amoB2 genes are about 99.1% identical (i.e., at
1254/1266 positions). Accordingly, in some embodiments, the amoB2
nucleic acid comprises D23 nucleotides at at least 1, 2, 3, 4, 5,
6, 7, 8, 9, 10, 11, 12 or all of the positions that differ in this
gene between strains C91 and D23. In embodiments, the amoB2 nucleic
acid comprises D23 nucleotides at at most 1, 2, 3, 4, 5, 6, 7, 8,
9, 10, 11, 12 or all of the positions that differ in this gene
between strains C91 and D23. In embodiments, the amoB2 nucleic acid
comprises a sequence at least about 99.1%, 99.2%, 99.4%, 99.6%,
99.8%, or 100% identical to the D23 amoB2 gene.
[0561] The amoC1 genes are about 99.8% identical (i.e., at 814/816
positions). Accordingly, in some embodiments, the amoC1 nucleic
acid comprises D23 nucleotides at at least 1, 2, or all of the
positions that differ in this gene between strains C91 and D23. In
embodiments, the amoC1 nucleic acid comprises D23 nucleotides at at
most 1, 2, or all of the positions that differ in this gene between
strains C91 and D23. In embodiments, the amoC1 nucleic acid
comprises a sequence at least about 99.8%, 99.9%, or 100% identical
to the D23 amoC1 gene.
[0562] The amoC2 genes are about 99.8% identical (i.e., at 814/816
positions). Accordingly, in some embodiments, the amoC2 nucleic
acid comprises D23 nucleotides at at least 1, 2, or all of the
positions that differ in this gene between strains C91 and D23. In
embodiments, the amoC2 nucleic acid comprises D23 nucleotides at at
most 1, 2, or all of the positions that differ in this gene between
strains C91 and D23. In embodiments, the amoC2 nucleic acid
comprises a sequence at least about 99.8%, 99.9%, or 100% identical
to the D23 amoC2 gene.
[0563] The amoC3 genes are about 98.9% identical (i.e., at 816/825
positions). Accordingly, in some embodiments, the amoC3 nucleic
acid comprises D23 nucleotides at at least 1, 2, 3, 4, 5, 6, 7, 8,
9, or all of the positions that differ in this gene between strains
C91 and D23. In embodiments, the amoC3 nucleic acid comprises D23
nucleotides at at most 1, 2, 3, 4, 5, 6, 7, 8, 9, or all of the
positions that differ in this gene between strains C91 and D23. In
embodiments, the amoC3 nucleic acid comprises a sequence at least
about 98.9%, 99.0%, 99.2%, 99.4%, 99.6%, 99.8%, or 100% identical
to the D23 amoC3 gene.
[0564] The hao1 genes are about 99.0% identical (i.e., at 1696/1713
positions). Accordingly, in some embodiments, the hao1 nucleic acid
comprises D23 nucleotides at at least 1, 2, 3, 4, 5, 6, 7, 8, 9,
10, 11, 12, 13, 14, 15, 16, 17, or all of the positions that differ
in this gene between strains C91 and D23. In embodiments, the hao1
nucleic acid comprises D23 nucleotides at at most 1, 2, 3, 4, 5, 6,
7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, or all of the positions
that differ in this gene between strains C91 and D23. In
embodiments, the hao1 nucleic acid comprises a sequence at least
about 99.0%, 99.2%, 99.4%, 99.6%, 99.8%, or 100% identical to the
D23 hao1 gene.
[0565] The hao2 genes are about 99.4% identical (i.e., at 1702/1713
positions). Accordingly, in some embodiments, the hao2 nucleic acid
comprises D23 nucleotides at at least 1, 2, 3, 4, 5, 6, 7, 8, 9,
10, 11, or all of the positions that differ in this gene between
strains C91 and D23. In embodiments, the hao2 nucleic acid
comprises D23 nucleotides at at most 1, 2, 3, 4, 5, 6, 7, 8, 9, 10,
11, or all of the positions that differ in this gene between
strains C91 and D23. In embodiments, the hao2 nucleic acid
comprises a sequence at least about 99.4%, 99.6%, 99.8%, or 100%
identical to the D23 hao2 gene.
[0566] The hao3 genes are about 99.2% identical (i.e., at 1700/1713
positions). Accordingly, in some embodiments, the hao3 nucleic acid
comprises D23 nucleotides at at least 1, 2, 3, 4, 5, 6, 7, 8, 9,
10, 11, 12, 13, or all of the positions that differ in this gene
between strains C91 and D23. In embodiments, the hao3 nucleic acid
comprises D23 nucleotides at at most 1, 2, 3, 4, 5, 6, 7, 8, 9, 10,
11, 12, 13, or all of the positions that differ in this gene
between strains C91 and D23. In embodiments, the hao3 nucleic acid
comprises a sequence at least about 99.2%, 99.4%, 99.6%, 99.8%, or
100% identical to the D23 hao3 gene.
[0567] The cycA1 genes are about 98.0% identical (i.e., at 694/708
positions). Accordingly, in some embodiments, the cycA1 nucleic
acid comprises D23 nucleotides at at least 1, 2, 3, 4, 5, 6, 7, 8,
9, 10, 11, 12, 13, 14, or all of the positions that differ in this
gene between strains C91 and D23. In embodiments, the cycA1 nucleic
acid comprises D23 nucleotides at at most 1, 2, 3, 4, 5, 6, 7, 8,
9, 10, 11, 12, 13, 14, or all of the positions that differ in this
gene between strains C91 and D23. In embodiments, the cycA1 nucleic
acid comprises a sequence at least about 98.0%, 98.2%, 98.4%,
98.6%, 98.8%, 99.0%, 99.2%, 99.4%, 99.6%, 99.8%, or 100% identical
to the D23 cycA1 gene.
[0568] The cycA2 genes are about 98.7% identical (i.e., at 699/708
positions). Accordingly, in some embodiments, the cycA2 nucleic
acid comprises D23 nucleotides at at least 1, 2, 3, 4, 5, 6, 7, 8,
9, 10, 11, or all of the positions that differ in this gene between
strains C91 and D23. In embodiments, the cycA2 nucleic acid
comprises D23 nucleotides at at most 1, 2, 3, 4, 5, 6, 7, 8, 9, 10,
11, or all of the positions that differ in this gene between
strains C91 and D23. In embodiments, the cycA2 nucleic acid
comprises a sequence at least about 98.7%, 98.8%, 99.0%, 99.2%,
99.4%, 99.6%, 99.8%, or 100% identical to the D23 cycA2 gene.
[0569] The cycA3 genes are about 99.3% identical (i.e., at 703/708
positions). Accordingly, in some embodiments, the cycA3 nucleic
acid comprises D23 nucleotides at at least 1, 2, 3, 4, 5, or all of
the positions that differ in this gene between strains C91 and D23.
In embodiments, the cycA3 nucleic acid comprises D23 nucleotides at
at most 1, 2, 3, 4, 5, or all of the positions that differ in this
gene between strains C91 and D23. In embodiments, the cycA3 nucleic
acid comprises a sequence at least about 99.3%, 99.4%, 99.6%,
99.8%, or 100% identical to the D23 cycA3 gene.
[0570] The cycB1 genes are about 96.7% identical (i.e., at 696/720
positions). Accordingly, in some embodiments, the cycB1 nucleic
acid comprises D23 nucleotides at at least 1, 2, 3, 4, 5, 6, 7, 8,
9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25,
26, or all of the positions that differ in this gene between
strains C91 and D23. In embodiments, the cycB1 nucleic acid
comprises D23 nucleotides at at most 1, 2, 3, 4, 5, 6, 7, 8, 9, 10,
11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, or
all of the positions that differ in this gene between strains C91
and D23. In embodiments, the cycB1 nucleic acid comprises a
sequence at least about 96.7%, 96.8%, 97.0%, 97.2%, 97.4%, 97.6%,
97.8%, 98.0%, 98.2%, 98.4%, 98.4%, 98.6%, 98.8%, 99.0%, 99.2%,
99.4%, 99.6%, 99.8%, or 100% identical to the D23 cycB1 gene.
[0571] The cycB2 genes are about 97.1% identical (i.e., at 702/723
positions). Accordingly, in some embodiments, the cycB2 nucleic
acid comprises D23 nucleotides at at least 1, 2, 3, 4, 5, 6, 7, 8,
9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, or all of the
positions that differ in this gene between strains C91 and D23. In
embodiments, the cycB2 nucleic acid comprises D23 nucleotides at at
most 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18,
19, 20, 21, or all of the positions that differ in this gene
between strains C91 and D23. In embodiments, the cycB2 nucleic acid
comprises a sequence at least about 97.1%, 97.2%, 97.4%, 97.6%,
97.8%, 98.0%, 98.2%, 98.4%, 98.4%, 98.6%, 98.8%, 99.0%, 99.2%,
99.4%, 99.6%, 99.8%, or 100% identical to the D23 cycB2 gene.
[0572] Further provided herein are vectors comprising nucleotide
sequences described herein. In some embodiments, the vectors
comprise nucleotides encoding a protein described herein. The
vectors include, but are not limited to, a virus, plasmid, cosmid,
lambda phage or a yeast artificial chromosome (YAC). Such vectors
may include a promoter, an open reading frame with or without
introns, and a termination signal.
[0573] The present disclosure also provides host cells comprising a
nucleic acid as described herein, or a nucleic acid encoding a
protein as described herein.
[0574] In certain embodiments, the host cells are genetically
engineered by using an expression cassette. The phrase "expression
cassette," refers to nucleotide sequences, which are capable of
affecting expression of a gene in hosts compatible with such
sequences. Such cassettes may include a promoter, an open reading
frame with or without introns, and a termination signal. Additional
factors necessary or helpful in effecting expression may also be
used, such as, for example, an inducible promoter.
[0575] The disclosure also provides host cells comprising the
vectors described herein.
[0576] The cell can be, but is not limited to, a eukaryotic cell, a
bacterial cell, an insect cell, or a human cell. If the cell is a
bacterial cell, it may be, e.g., E. coli or an ammonia-oxidizing
bacterium such as Nitrosomonas (e.g., N. eutropha or N. europaea),
Nitrosococcus, Nitrosospira, Nitrosocystis, Nitrosolobus, and
Nitrosovibrio.
9. ADJUSTING THE SKIN MICROBIOME WITH AMMONIA OXIDIZING
BACTERIA
[0577] The present disclosure provides for systems and methods for
changing the skin microbiome, e.g., the human skin microbiome. The
systems and methods may provide treatment of infections or
conditions, e.g., related to the skin, e.g., skin infections and/or
skin conditions.
[0578] Ammonia-oxidizing bacteria (AOB) of the genus Nitrosomonas
are Gram-negative obligate autotrophic bacteria with a unique
capacity to generate nitrite and nitric oxide exclusively from
ammonia as an energy source. They are widely present both in soil
and water environments and are essential components of
environmental nitrification processes. Due to the roles of nitrite
and nitric oxide on human skin as important components of several
physiological functions, such as vasodilation, skin inflammation
and wound healing, these bacteria may have beneficial properties
for both healthy and immunopathological skin conditions. These
bacteria may be safe for use in humans because they are
slow-growing, cannot grow on organic carbon sources, may be
sensitive to soaps and antibiotics, and have never been associated
with any disease or infection in animals or humans.
[0579] Topical application of ammonia oxidizing bacteria to a
subject, e.g., a human subject may lead to unexpected changes in
the skin microbiome, and more specifically it may lead to increases
in the proportion of normal commensal non-pathogenic species and
reductions in the proportion of potentially pathogenic, pathogenic,
or disease causing organisms.
EXAMPLES
Example 1
Initial Culturing of N. eutropha
[0580] A soil-derived culture enriched in various ammonia oxidizing
bacteria was applied to the skin of an adult male subject as
described in WO/2003/057380. The period of growth on the human body
selected for a strain with the capacity to colonize human skin for
an extended period of time. After several months, the strain was
re-isolated from the skin of the individual and cultured in
laboratory conditions for a sustained period as described in the
subsequent examples. While not wishing to be bound by theory, it is
believed that the sustained laboratory culture selected for new
mutations improving the strain properties, e.g., improved tolerance
for high-ammonia conditions.
Example 2
Growing and Monitoring D23 or Mixtures of Strains that Comprise D23
Culture Conditions
[0581] D23 can be grown in batches or by continuous cultivation in
a bioreactor. Batch preparation uses the medium of Table 3.
TABLE-US-00003 TABLE 3 Growth Medium for Batch culturing:
Weight/Volume Final Concentration (in~1.5 L) (in~1.5 L)
(NH.sub.4).sub.2SO.sub.4 4.95 g 50 mM NH.sub.4.sup.+ (MW 132.14)
KH.sub.2PO.sub.4 (MW 136.1) 0.616 g 3.0 mM 1M MgSO.sub.4 1.137 ml
0.76 mM 1M CaCl.sub.2 0.3 ml 0.2 mM 30 mM FeCl.sub.3/50 mM 0.5 ml
10 .mu.M/16.7 .mu.M EDTA 50 mM CuSO.sub.4 30 .mu.l 1.0 .mu.M Add
1400 ml ddH.sub.2O to flask. Autoclave. Store at room temperature.
After autoclaving add: Phosphate Buffer 100 ml 32 mM
KH.sub.2PO.sub.4/ 2.7 mM NaH.sub.2PO.sub.4.cndot.H.sub.2O 5%
Na.sub.2CO.sub.3 12 ml 0.04%
[0582] The medium of Table 3 is inoculated with .about.15 ml of a 3
day old culture of D23 (i.e. 1% volume). The cultures are incubated
in the dark at 30.degree. C. by shaking at 200 rpm.
[0583] Often, a N. eutropha D23 mixed culture is grown on complete
N. europaea media. The culture medium is described below, and
additional details on culturing ammonia-oxidizing bacteria are
available on the World Wide Web at
nitrificationnetwork.org/Nerecipe.php, Ensign et al., 1993, and
Stein & Arp, 1998.
Step 1.
[0584] Add 900 ml of deionized water to a 2-liter Erlenmeyer
flask.
[0585] Add in sequence:
[0586] 3.3 g (NH.sub.4.sup.+).sub.2SO.sub.4 (50 mM);
[0587] 0.41 g KH.sub.2PO.sub.4
[0588] 0.75 ml 1 M MgSO.sub.4 stock solution
[0589] 0.2 ml 1 M CaCl.sub.2 stock solution
[0590] 0.33 ml 30 mM FeSO.sub.4/50 mM EDTA stock solution
[0591] 0.01 ml 50 mM CuSO.sub.4 stock solution
[0592] Sterilize the solution by autoclaving.
Step 2.
[0593] Add 400 ml of deionized water to a beaker. Add:
[0594] 27.22 g KH.sub.2PO.sub.4
[0595] 2.4 g NaH.sub.2PO.sub.4
[0596] Adjust the pH to 8.0 with 10 N NaOH, and bring the final
volume to 500 ml with deionized water.
[0597] Sterilize 100 ml fractions of the solution by autoclaving in
250-500 ml Erlenmeyer flasks.
Step 3
[0598] Prepare 500 ml of 5% (w/v) Na.sub.2CO.sub.3 (anhydrous)
[0599] Sterilize the solution by autoclaving.
Step 4
[0600] Add 1.times.100 ml aliquot of solution prepared in Step 2 to
the flask prepared in Step 1.
Step 5
[0601] Add 8 ml of the solution prepared in Step 3 to the flask
prepared in Step 1.
[0602] The D23 can also be cultured continuously in a bioreactor.
Table 4 describes the appropriate media.
TABLE-US-00004 TABLE 4 Growth Medium for continuous culture: Batch
medium Feeding solution Weight/Volume (1 L) Weight/Volume (1 L)
(Final concentration) (Final concentration)
(NH.sub.4).sub.2SO.sub.4 (MW 132.14) 3.3 g 13.2 g (50 mM
NH.sub.4.sup.+) (200 mM NH.sub.4.sup.+) KH.sub.2PO.sub.4 (MW 136.1)
1.23 g 0.41 g (9.0 mM) (3.0 mM) 1M MgSO.sub.4 0.758 ml 0.758 ml
(0.76 mM) (0.76 mM) 1M CaCl.sub.2 0.2 ml 0.2 ml (0.2 mM) (0.2 mM)
30 mM FeCl.sub.3/50 mM EDTA 0.333 ml 0.333 ml (10 .mu.M/16.7 .mu.M)
(10 .mu.M/16.7 .mu.M) 50 mM CuSO.sub.4 20 .mu.l 20 .mu.l (1.0
.mu.M) (1.0 .mu.M) ddH.sub.2O 1000 ml 1000 ml Autoclave each
solution and store at room temperature.
[0603] The batch media, in a bioreactor vessel, is inoculated with
.about.10 ml of a 3 day old N. eutropha D23 culture (i.e. 1%
volume). The pH is adjusted to 7.6 using 7.5% Na.sub.2CO.sub.3 The
bioreactor is run in batch mode with below parameters: pH: 7.6
(lower limit: 7.45 & upper limit: 7.8), Temperature: 28.degree.
C. (lower limit: 25.degree. C. & upper limit: 32.degree. C.),
DO (dissolved oxygen): 45% (lower limit: 10%, upper limit: 100%),
Stirrer: 550 rpm.
[0604] The OD600 nm of the culture in the bioreactor reaches 0.15
to 0.18 in 3-4 days. At this point, the culture will consume most
of the 50 mM NH.sub.4+ present in the AOB growth media, and a user
should start feeding the bioreactor with feeding solution at 0.59
ml/min (.about.10%). The outflow pump should also be turned on at
0.59 ml/min (.about.10%). The OD600 nm of the bioreactor reaches
0.5-0.6 in 1-2 days of continuous culture. The culture in the
bioreactor is tested for heterotrophic contaminants by plating 1 ml
of the bioreactor outflow on an LB plate.
Monitoring Growth of N. eutropha D23
[0605] Growth of N. eutropha D23 cells is monitored by measuring
the OD600 nm of the culture. Typical growth in a batch culture as
measured by OD600 nm is between 0.06 to 0.08.
[0606] The AOB growth medium contains NH.sub.4+ that is
stoichiometrically converted to NO.sub.2- by N. eutropha D23.
Another way to monitor the growth of N. eutropha is to follow the
release of nitrite (NO.sub.2-) in the growth medium. NO.sub.2-
concentration is determined with Griess reagents, sulfanilamide and
N-naphthylethylenediamine (also called NNEQ). Briefly,
sulfanilamide and NNEQ are added to a sample and to known
concentrations of sodium nitrite that make up a standard curve.
Samples are incubated in the dark for 30 minutes. The absorbance is
read at 540 nm.
[0607] Another way to follow nitrite production is by using a
spectrophotometer by monitoring the optical density (OD) difference
between 352 nm and 400 nm. The nitrite concentration is determined
using a millimolar extinction coefficient of 0.0225 mM.sup.-1. This
assay can be performed directly by sampling the medium with the
cells.
NO.sub.2- concentration (mM)=(OD.sub.352-OD.sub.400)/0.0225
[0608] The growth of a mixed culture comprising D23 was monitored
by measuring optical density at 600 nm (OD600 nm) and by measuring
Nitrite (NO.sub.2.sup.-), and the growth rate is shown in FIGS. 1
and 2. FIG. 1 shows that the optical density at a 600 nm wavelength
plateaus slightly below 0.1, after 3 to 4 days. FIG. 2A shows that
the amount of nitrite produced plateaus slightly below 25 mM after
3 to 4 days. NO.sub.2.sup.- concentrations in the cultures were
determined colorimetrically by the Griess reagent (Hageman &
Hucklesby, 1971), and is used as a second indicator for the growth
rates and growth phases since the accumulation of NO.sub.2.sup.- is
consistently proportional to the increase in cell mass during
growth.
[0609] In FIG. 2B-I, increasing densities of D23 harvested from
continuous culture were suspended in medium supplemented with 50 mM
NH.sub.4.sup.+ and grown shaking at 30.degree. C. for 48 hours.
Nitrite production was measured in supernatant samples using the
Griess assay at the time points indicated. Results shown are mean
values.+-.SD from three independent experiments.
[0610] In FIG. 2B-II. Nitrite production by N. eutropha D23 in
vitro is shown. Increasing densities of D23 were suspended in
mineral salt medium supplemented with 50 mM NH.sub.4.sup.+ and
grown shaking at 30.degree. C. for 24 hr. Nitrite production was
measured in supernatant samples using the Griess assay at the time
points indicated.
[0611] Storage Conditions
[0612] N. eutropha suspensions obtained from the continuous culture
system showed remarkable stability upon storage at 4.degree. C. for
several months, as indicated by the highly consistent nitrite
concentrations generated upon subculture under batch growth
conditions. Protocols for storing and recovering N. eutropha are
set out below.
[0613] Obtain 500 ml of a N. eutropha D23 culture grown to
late-exponential phase (OD600=0.5-0.6 in continuous culture).
Centrifuge at 10,000.times.g for 15 min at 20.degree. C. Remove
supernatant and resuspend the pellet in 50 ml of AOB storage
buffer. Spin as above. Remove supernatant and resuspend thoroughly
in a total of 50 ml storage buffer. This would be the 10.times. AOB
stock. Store upright at 4.degree. C. in 50 ml polypropylene
tubes.
[0614] AOB Storage Buffer (for AOB storage at 4.degree. C.): 50 mM
Na.sub.2HPO.sub.4-2 mM MgCl.sub.2 (pH 7.6) can be made as
follows.
[0615] In 1 Liter ddH2O: Na.sub.2HPO.sub.4-7.098 g
[0616] MgCl.sub.2-0.1904 g
[0617] Adjust pH to 7.6. Filter-sterilize.
[0618] N. eutropha may be cryopreserved as follows. Transfer 1.25
ml of N. eutropha D23 mid-log culture to a 2 ml cryotube and 0.75
ml of sterile 80% glycerol. Shake tubes gently, incubate at room
temperature for 15 min to enable uptake of the cryoprotective
agents by the cells. Then, put tubes directly in a -80oC freezer
for freezing and storage. For resuscitation of cultures, thaw
frozen stocks on ice for 10-20 minutes. Centrifuge, at
8,000.times.g for 3 minutes at 4.degree. C. Discard supernatant and
wash the pellet by suspending it in 2 ml AOB medium followed by
another centrifugation at 8,000.times.g for 3 minutes at 4.degree.
C. to reduce potential toxicity of the cryoprotective agents in
subsequent growth experiments. Discard the supernatant and
resuspend the pellet in 2 ml of AOB medium, inoculate into 50 ml of
AOB medium containing 50 mM NH.sub.4.sup.+, and incubate in dark at
30.degree. C. by shaking at 200 rpm.
[0619] In FIG. 2C, stability upon storage at 4.degree. C. was
studied. N. eutropha D23 previously harvested from continuous
culture and stored at 4.degree. C. was inoculated at 10.sup.9
CFU/ml in mineral salt medium supplemented with 50 mM
NH.sub.4.sup.+ and grown shaking at 30.degree. C. Nitrite
production was determined at 24 and 48 hours post-incubation (left
and right panel, respectively). Data shown are representative of a
D23 suspension sampled repeatedly over a 6-month period.
Example 3
Creation of an Axenic D23 Culture
[0620] To isolate N. eutropha D23 in pure culture, four types of
media (described below) were made, autoclaved and poured in plates.
Sterile nylon membranes were placed on the plates.
N. europaea media+1.2% R.sub.2A agar N. europaea media+1.2% agar N.
europaea media+1.2% agarose N. europaea media+1.2% agarose+0.3 g/L
pyruvate
[0621] 3 day old N. eutropha D23 culture was streaked onto the
nylon membranes and the plates were incubated at 30.degree. C. The
plates were monitored daily for growth of red colored N. eutropha
cells. Nylon membranes were transferred to fresh plates once a
week.
[0622] Reddish colored colonies appeared on plates with R.sub.2A
agar or agar by end of 1 week. Single colonies were picked from
plates with R2A agar and grown in N. europaea media. The cultures
grew well in 6 days to 0.08 OD600 nm. Heterotrophic colonies
appeared when the culture was plated on LB-Agar plates.
[0623] Reddish colored colonies on plates with R.sub.2A agar, agar,
agarose, or agarose+pyruvate appeared by end of 2 weeks. Single
colonies were picked from plates with agar or agarose and grown in
N. europaea media. The cultures grew well in 6-8 days to 0.08 OD600
nm. Heterotrophic colonies appeared when the culture was plated on
LB-Agar plates.
[0624] Bright reddish colonies on plates with R.sub.2A agar, agar,
agarose, or agarose+pyruvate appeared by end of 4 weeks. Single
colonies were picked from plates with agarose and grown in N.
europaea media. The cultures grew well in 6-8 days to 0.08 OD600
nm. White colonies appeared when the culture was plated on LB-Agar
plates.
[0625] Contaminating bacteria (e.g., non-N. eutropha bacteria
present in the mixed culture) were identified by culturing,
amplifying 16S rRNA by PCR, and sequencing of the PCR products.
Contaminants were identified as Microbacterium sp. and
Alcaligenaceae bacterium.
[0626] To create an axenic culture of D23 (i.e., free of
contaminating bacteria) serial dilution was used. Eight single
colonies (designated A-H) were picked, and each was placed into a
10 ml culture of N. europae medium. For each culture, five
sequential 1:10 dilutions were created. For each culture A-H,
growth was observed in the two or three most concentrated of the
dilutions.
[0627] A second serial dilution was carried out. 50 ml of media was
inoculated with approximately 2.times.10.sup.8 N. eutropha cells,
and sequential dilutions of 1:50 were made, such that after the
fifth dilution, a flask was expected to have approximately one
cell. Flasks that exhibited bacterial growth were plated on LB-agar
to assay for contaminating bacteria, and no contaminating bacteria
were observed. In addition, no contaminating gram positive cells
were observed under the microscope.
[0628] Accordingly, the serial dilution process yielded an axenic
or substantially axenic culture of N. eutropha.
Example 4
Sequencing of the D23 Genome
[0629] Strain D23 was obtained as described in Example 1, and was
made axenic as described in Example 3.
[0630] A 10 ml aliquot the bacterial sample was inoculated into
approximately 1 L of N. europaea growth medium described in Example
2. The culture grew well to optical density of 0.08 at 600 nm in a
batch culture in 3 days.
[0631] Total DNA of the culture was prepared and sequenced using
Illumina.RTM. technology and/or SMRT.RTM. DNA Sequencing System
technology, Pacific Biosciences. The strain was identified as
Nitrosomonas eutropha and was designated D23.
[0632] The genome sequence of D23 was compared to that of N.
eutropha C91, which is believed to be the only other sequenced
strain of N. eutropha.
[0633] The length of the D23 chromosome is 2,537,572 base pairs,
which is shorter than the 2,661,057 base pair chromosome of N.
eutropha strain C91 chromosome. Based on the 16S-23S operon, strain
D23 has 99.46% identity to C91 and 95.38% identity to N. europaea.
DNA sequencing of N. eutropha D23 indicated that this strain lacks
plasmids. This contrasts with the sequence of strain C91, which has
two plasmids.
[0634] Protein-encoding regions and RNA-encoding sequences were
identified by sequence analysis. Supplementary Table 1 is a table
of annotations that lists the positions of 2,777 genes in the D23
genome (SEQ ID NO: 1).
[0635] On the level of individual genes, several genes are present
in D23 that are absent in C91. These genes are summarized in FIGS.
6-8. FIG. 6 is a table displaying unique D23 genes with an assigned
ORF number and a function based on sequence analysis, or a
hypothetical gene above 200 base pairs in length. There are 162
genes in this category. FIG. 7 is a table displaying unique D23
genes below 200 base pairs that have an assigned ORF number. There
are 164 of these genes. FIG. 8 is a table displaying unique D23
genes with no assigned ORF number. There are 219 of these genes (of
which 180 are below 200 bp in length).
[0636] Strain D23 also lacks a number of genes that are present (or
lack close homologs) in strain C91. These genes are sometimes
referred to as unique C91 genes. These genes include the about 300
genes listed in FIG. 9.
[0637] D23 contains several ammonia metabolism genes that differ
from their homologs in C91. Certain of these genes are enumerated
in Table 1 of the Detailed Description. Sequence alignments were
performed between the D23 proteins and their homologs in strain
C91. The sequence alignments are shown in FIGS. 10-16 and sequence
differences between the two strains are shown in Table 2 of the
Detailed Description.
[0638] The sequence comparisons revealed the percent sequence
identities between the C91 and D23 homologs of each protein. More
specifically, FIG. 10 is an alignment between AmoA1 and AmoA2 of
strains C91 and D23. Each protein is identical at 273/276 residues,
and so each is about 98.9% identical between strains. FIG. 11 is an
alignment between AmoB1 and AmoB2 of strains C91 and D23. Both
proteins are identical at 419/421 positions, and so are about 99.5%
identical between strains. FIG. 12 is an alignment between AmoC1
and AmoC2 of strains C91 and D23. Both proteins are identical
throughout. FIG. 13 is an alignment between AmoC3 of strains C91
and D23. This protein is identical at 272/274 positions, and so are
about 99.3% identical between strains.
[0639] As to the Hao proteins, FIG. 14 (A and B) is an alignment
between Hao1, Hao2, and Hao3 of strains C91 and D23. Hao1 is
identical at 567/570 positions, and so each is about 99.5%
identical between strains. Hao2 and Hao3 are each identical at
568/570 positions, and so are about 99.6% identical between
strains.
[0640] Turning now to cytochrome c554 proteins, FIG. 15 is an
alignment between CycA1, CycA2, and CycA3 of strains C91 and D23.
CycA1 is identical at 233/235 positions, and so is about 99.1%
identical between strains. CycA2 and CycA3 are each identical at
234/235 positions, and so each is about 99.6% identical between
strains.
[0641] As to the cytochrome c.sub.M552 proteins, FIG. 16 is an
alignment between CycB1 and CycB2 of strains C91 and D23. CycB1 is
identical at 232/239 positions, and so is about 97.1% identical
between strains. CycB2 is identical at 236/239 positions, and so is
about 98.7% identical between strains. Here, the length of the
protein is considered 239 amino acids because that is its length in
strain D23.
[0642] Alignment of the nucleic acid sequences of Table 1 shows the
percent identity between homologs in C91 and D23. The amoA1 genes
are about 98.8% identical (i.e., at 821/831 positions), the amoA2
genes are about 98.8% identical (i.e., at 821/831 positions), the
amoB1 genes are about 99.1% identical (i.e., at 1255/1266
positions), the amoB2 genes are about 99.1% identical (i.e., at
1254/1266 positions), the amoC1 genes are about 99.8% identical
(i.e., at 814/816 positions), the amoC2 genes are about 99.8%
identical (i.e., at 814/816 positions), and the amoC3 genes are
about 98.9% identical (i.e., at 816/825 positions). The hao1 genes
are about 99.0% identical (i.e., at 1696/1713 positions), the hao2
genes are about 99.4% identical (i.e., at 1702/1713 positions), and
the hao3 genes are about 99.2% identical (i.e., at 1700/1713
positions). Of the cytochrome c554 genes, the cycA1 genes are about
98.0% identical (i.e., at 694/708 positions), the cycA2 genes are
about 98.7% identical (i.e., at 699/708 positions), and the cycA3
genes are about 99.3% identical (i.e., at 703/708 positions). Of
the cytochrome c.sub.M552 genes, the cycB1 genes are about 96.7%
identical (i.e., at 696/720 positions) and the cycB2 genes are
about 97.1% identical (i.e., at 702/723 positions).
Example 5
Competitive Growth Studies
[0643] A study was designed to determine whether N. eutropha strain
D23 could inhibit the growth of undesirable bacteria such as
Pseudomonas aeruginosa (P. aeruginosa or PA), Staphylococcus aureus
(S. aureus or SA), Streptococcus pyogenes (S. pyogenes or SP),
Acinetobacter baumannii (A. baumannii or AB), and Propionibacterium
acnes, all of which are important pathogenic agents frequently
isolated from either one or both of infected skin and wound sites.
This protocol may also be used to test other N. eutropha strains
for the ability to inhibit the growth of undesirable bacteria.
[0644] Briefly, a suitable protocol can comprise the following
steps. At t=0, a culture is inoculated with N. eutropha, and then
the N. eutropha is incubated for 24 hours. Culture characteristics
(e.g., pH and nitrite levels) are assayed. At t=24 hours, the
undesirable bacterium is added to the culture. Immediately upon
addition, samples are obtained for determining CFU/ml of the
undesirable bacteria and optionally CFU/ml of N. eutropha, pH, and
nitrite levels. Incubation is allowed to proceed for an additional
24 hours. At subsequent timepoints, e.g., t=30 and t=48, one can
take the same measurements as at t=24. To determine CFU/ml, one can
plate neat/-1/-2/-3/-4/-5 (or higher) to obtain accurate
counts.
[0645] A more detailed protocol is set out below.
Day 1
[0646] 1. Mix the 10.times.AOB stock suspension stored at 4.degree.
C. by inverting several times until a homogenous suspension is
obtained. [0647] 2. Aliquot 10 ml of the suspension in 8.times.1.5
ml polypropylene tubes. [0648] 3. Centrifuge at 17,000.times.g for
3 min at room temperature. [0649] 4. Remove supernatant and any
residual buffer from each pellet and resuspend all pellets
thoroughly into a total of 10 ml complete AOB medium in a 50 ml
polypropylene tube. [0650] 5. Pipet 5 ml of 10.times.AOB suspension
in each of two 50 ml polypropylene tubes (Tube 1-2). [0651] 6.
Prepare five additional tubes (Tube 4-8) containing 10.times.AOB
suspensions in complete AOB medium/0.5.times. Phosphate Buffer.
Aliquot 26 ml of the 10.times.AOB stock suspension in 16.times.1.5
ml polypropylene tubes. Obtain pellets as above and resuspend in a
total of 26 ml complete AOB medium/0.5.times. Phosphate Buffer in a
50 ml polypropylene tube. [0652] 7. Pipet 5 ml of the 10.times.AOB
suspension in each of five 50 ml polypropylene tubes (Tube 4-8).
[0653] 8. Also, prepare two tubes with 10.times. Heat-killed AOB
suspensions in either complete AOB medium (Tube 3) or complete AOB
medium/0.5.times. Phosphate Buffer (Tube 9). Aliquot 10 ml of the
Heat-killed suspension stored at 4.degree. C. in 8.times.1.5 ml
polypropylene tubes. Centrifuge at 17,000.times.g for 3 min at room
temperature and remove supernatant, as described above for live
AOB. Resuspend four pellets in a total of 5 ml complete AOB medium
in one 50 ml polypropylene tube (Tube 3) and the remaining four
pellets in a total of 5 ml complete AOB medium/0.5.times. Phosphate
Buffer in a second 50 ml polypropylene tube (Tube 9). [0654] 9. Add
141 .mu.l of 1 M ammonium sulfate to obtain 25 mM final
concentration (Tube 1, 3, 4, 5, 9). Add an equal volume of
dH.sub.2O to corresponding control tubes (Tube 2, 6, 7). [0655] 10.
To Tube 8, add 141 .mu.l of fresh 1 M NaNO.sub.2. [0656] 11. Swirl
all tubes gently, but thoroughly, to mix. [0657] 12. Immediately
after mixing each suspension, remove 0.5 ml from each tube and
centrifuge all samples at 17,000.times.g, 3 min, RT. Transfer
supernatants into fresh tubes after completing step 13, and measure
both pH and nitrite levels using Griess Reagent to obtain TO
values. [0658] 13. Incubate all 50 ml tubes at 30.degree. C. with
mixing on an orbital shaker at 150 rpm (upright position) for 24
hr.
TABLE-US-00005 [0658] TABLE 5 T0 10x T24 10x Killed 1M 1M SA/PA AOB
AOB (NH.sub.4).sub.2SO.sub.4 H.sub.2O NaNO.sub.2 in saline SAMPLE
Tube (ml) (ml) (.mu.l) (.mu.l) (.mu.l) (ml) Complete AOB medium 10x
AOB + NH.sub.4.sup.+ 1 5 -- 141 -- -- 0.5 10x AOB 2 5 -- -- 141 --
0.5 10x Killed AOB + 3 -- 5 141 -- -- 0.5 NH.sub.4.sup.+ Complete
AOB medium/0.5x Phosphate Buffer 10x AOB + NH.sub.4.sup.+ 4 5 --
141 -- -- 0.5 10x AOB + NH.sub.4.sup.+ 5 5 -- 141 -- -- 0.5 10x AOB
6 5 -- -- 141 -- 0.5 10x AOB 7 5 -- -- 141 -- 0.5 10x AOB +
NaNO.sub.2 8 5 -- -- -- 141 0.5 10x Killed AOB + 9 -- 5 141 -- --
0.5 NH.sub.4.sup.+
Day 2
[0659] 14. At 24 hr, prepare SA, PA, SP or AB inocula to add to the
suspensions. [0660] 15. From an overnight (20-24 hr) SA or PA
culture grown on Tryptic Soy Agar (TSA), or a SP or AB culture
prepared on Brain Heart Infusion (BHI) Agar, prepare bacterial
suspension in Tryptic Soy Broth (TSB) or BHI broth (BHIB) at
.about.2.times.10.sup.8 CFU/ml. [0661] 16. Pipet 50 .mu.l of the
SA/PA/SP/AB suspension in 9.95 ml saline to obtain .about.10.sup.6
CFU/ml. Keep on ice, as needed. [0662] 17. Vortex SA/PA/SP/AB
suspension and add 0.5 ml to Tube 1-9. [0663] 18. Swirl all tubes
gently, but thoroughly, to mix. [0664] 19. Immediately after mixing
each suspension, transfer 100 .mu.l from each tube into 0.9 ml TSB
or BHIB (10.sup.-1 dilution) to neutralize samples for CFU
determination. In addition, remove 0.5 ml from each tube and
centrifuge at 17,000.times.g, 3 min, RT. Recover supernatants in
fresh tubes after completing Step 20 and measure both pH and
nitrite levels using Griess Reagent after Step 21 to obtain T24
values. [0665] 20. Incubate all 50 ml tubes at 30.degree. C. with
mixing on an orbital shaker (150 rpm) for an additional 24 hr.
[0666] 21. Dilute T24 samples further in TSB or BHIB and plate
-2/-3/-4 dilutions on TSA or BHI agar. Incubate plates at
37.degree. C. for 24 hr to obtain SA, PA, SP, or AB viable counts.
[0667] 22. At 6 and 24 hr post-mixing of SA/PA/SP/AB with AOB,
vortex tubes and pipet 100 .mu.l samples into 0.9 ml TSB. Dilute
further in TSB or BHIB and plate neat through -5 dilutions on TSA
or BHI agar. At each time point, also remove 0.5 ml from each tube
and measure both pH and nitrite levels in each supernatant sample,
as described above. [0668] 23. Incubate TSA or BHI agar plates at
37.degree. C. for 24 hr to obtain T30 (6 hr) and T48 (24 hr) viable
counts. [0669] 24. Count CFU to determine % killing rates for each
time point
Griess Reagent Assay for Nitrite Quantification
[0670] 1. Use the 0.5 ml supernatant samples obtained for pH
determination at 0, 2, 6, and 24 hr. 2. Serially dilute 56 .mu.l of
the supernatant in 0.5 ml dH2O to obtain 10-100- and 1000-fold
dilutions, as needed. For TO samples, use 1/10 for Tube 1-6, 8, 9,
and 1/1000 for Tube 7. For T24/T30/T48 samples, use 1/10, 1/100,
1/1000 for all tubes, 3. To prepare sodium nitrite standards,
dilute 10 .mu.l of a fresh 1 M stock in 990 .mu.l complete AOB
medium-10% saline to obtain a 10 mM solution. 4. Dilute 10 .mu.l of
the 10 mM stock in 990 .mu.l dH.sub.2O to obtain a 100 .mu.M
working solution. 5. Prepare standards in dH.sub.2O as shown below.
Run standards only with TO samples.
TABLE-US-00006 TABLE 6 100 .mu.M Nitrite sodium nitrite dH.sub.2O
conc A.sub.540nm (.mu.l) (.mu.l) (.mu.M) (indicative values) 0
(blank) 500 0 0 62.5 437.5 12.5 0.307 125 375 25 0.607 250 250 50
1.164 500 0 100 2.35
6. To each 0.5 ml sample (or sodium nitrite standard), add 0.25 ml
each of Reagent A (58 mM sulfanilamide in 1.5 N HCl) and Reagent B
(0.77 mM n-(1-napthyl) ethylene diamine-2HCl in H.sub.2O
(light-sensitive; store in dark). 7. Mix and let stand at room
temperature for 30 min in the dark (or cover with foil). The color
should change to a vivid pink/violet. 8. Read absorbance at 540 nm
and determine nitrite concentrations from standard curve.
[0671] This protocol was used to test N. eutropha D23's ability to
inhibit the growth of P. aeruginosa (PA), S. aureus (SA), S.
pyogenes (SP), A. baumannii (AB), or P. acnes. The results of this
experiment are shown in FIGS. 3A, 3B, and 3C.
[0672] The left panel of FIG. 3A plots CFU/ml of PA versus time,
when PA is co-cultured with live N. eutropha and ammonium
(squares), live N. eutropha without ammonium (circles), killed N.
eutropha and ammonium (triangles), or live N. eutropha with
NaNO.sub.2 (inverted triangles). The right panel of FIG. 3A plots
CFU/ml of SA versus time, under the same conditions. The left panel
of FIG. 3B plots CFU/ml of SP versus time, under the same
conditions. The right panel of FIG. 3B plots CFU/ml AB versus time,
under the same conditions. FIG. 3C plots CFU/ml of P. acnes versus
time, when P. acnes is co-cultured with live N. eutropha and
ammonium (squares), live N. eutropha without ammonium (circles),
killed N. eutropha and ammonium (triangles), or live N. eutropha
with NaNO.sub.2 (inverted triangles). In all cases, live N.
eutropha with ammonium results in declining numbers of PA, SA, SP,
AB, or P. acnes whereas the other culture conditions allow the
undesirable bacteria to grow. Without being bound by theory, these
experiments suggest that nitrite generation from ammonia
concurrently with medium acidification by D23 led to strong
antibacterial effects, e.g., an approximately 100-fold reduction in
viable counts of methicillin-resistant Staphylococcus aureus,
Pseudomonas aeruginosa, Streptococcus pyogenes, Acinetobacter
baumannii, or P. acnes. By contrast, control co-cultures of
pathogenic bacteria either with heat-killed D23 supplemented with
ammonia, or with live D23 without ammonia, did not produce
comparable antibacterial effects. The control comprising live N.
eutropha culture without ammonium is consistent with the model that
N. eutropha's ammonia oxidation activity contributes to its
antibacterial effects. The control comprising killed N. eutropha
and ammonium indicates that some biological activity of the N.
eutropha (e.g., its ammonia oxidation activity) contributes to
antibacterial activity. The control comprising live N. eutropha
with NaNO.sub.2 indicates that comparable nitrite levels at neutral
pH (versus low pH when the bacteria use ammonia) do not have a
strong antimicrobial effect, and is consistent with the model that
N. eutropha's oxidation of ammonia, rather than nitrite alone,
contributes to the antibacterial activity.
[0673] The top panel of FIG. 4A plots the NO.sub.2.sup.-
concentration over time in the co-cultures described in the
paragraph above. NO.sub.2.sup.- concentration is an indication of
the rate of NH.sub.3 metabolism in the cultures. As above, PA is
co-cultured with N. eutropha and ammonium (squares), N. eutropha
without ammonium (circles), or killed N. eutropha and ammonium
(triangles). Live N. eutropha with ammonium produces dramatically
higher NO.sub.2.sup.- levels than the two control cultures,
indicating that the live N. eutropha converts ammonium into
NO.sub.2.sup.- under the culture conditions.
[0674] The bottom panel of FIG. 4A plots pH over time in the same
co-culturing conditions. pH indicates the metabolic activity of the
N. eutropha because the conversion of ammonia to nitrite produces
hydrogen ions. PA is co-cultured with N. eutropha and ammonium
(squares), N. eutropha without ammonium (circles), killed N.
eutropha and ammonium (triangles), or live N. eutropha with
NaNO.sub.2 (inverted triangles). Live N. eutropha with ammonium
acidifies the medium, in contrast to the three control cultures,
indicating that the live N. eutropha metabolizes ammonium under the
culture conditions.
[0675] The top panels of FIG. 4B plot the NO.sub.2.sup.-
concentration over time in the co-cultures described above.
NO.sub.2.sup.- concentration is an indication of the rate of
NH.sub.3 metabolism in the cultures. As above, S. pyogenes (SP) and
A. baumannii (AB) are co-cultured with N. eutropha and ammonium
(squares), N. eutropha without ammonium (circles), or killed N.
eutropha and ammonium (triangles). Live N. eutropha with ammonium
produces dramatically higher NO.sub.2 levels than the two control
cultures, indicating that the live N. eutropha converts ammonium
into NO.sub.2.sup.- under the culture conditions.
[0676] The bottom panels of FIG. 4B plot pH over time in the same
co-culturing conditions. pH indicates the metabolic activity of the
N. eutropha because the conversion of ammonia to nitrite produces
hydrogen ions. SP and AB are co-cultured with N. eutropha and
ammonium (squares), N. eutropha without ammonium (circles), killed
N. eutropha and ammonium (triangles), or live N. eutropha with
NaNO.sub.2 (inverted triangles). Live N. eutropha with ammonium
acidifies the medium, in contrast to the three control cultures,
indicating that the live N. eutropha metabolizes ammonium under the
culture conditions.
[0677] FIG. 4E shows an alternative visualization the data of FIGS.
4A and 4B.
[0678] The capacity of Nitrosomonas eutropha D23 to inhibit
proliferation of pathogenic bacteria due to nitrite production
concurrent with acidification (acidified nitrite) was assessed by
testing the survival of 5 strains of pathogenic bacteria in
co-culture studies with D23 in vitro. The five strains of
pathogenic bacteria included Propionibacterium acnes, Streptococcus
pyogenes, methicillin-resistant Staphylococcus aureus (MRSA),
Pseudomonas aeruginosa, and multidrug-resistant Acinetobacter
baumannii. Incubation of N. eutropha D23 (10.sup.10 cells/ml) in
the presence of ammonium led to nitrite concentrations of 10 mM or
higher and acidification to pH 6 or lower (FIG. 4B). The
combination of increased nitrite concentration and lowering of pH
led to bactericidal or bacteriostatic effects and a marked
reduction (up to 965-fold) in viable counts of the pathogenic
bacterial species tested. The results of these studies are
summarized in FIG. 4D and Table 7, below. In contrast to the D23
co-cultures incubated in the presence of ammonium, control
co-cultures of the five pathogenic agents with D23 without
ammonium, or with heat-killed D23 (B244) supplemented with
ammonium, did not lead to any inhibitory or antimicrobial
effects.
TABLE-US-00007 TABLE 7 Effect of N. eutropha D23 (D23) on relative
survival of pathogenic bacteria in vitro Relative Survival (Fold
Change) Heat-Killed Pathogen Tested AOB + NH.sub.3 AOB - NH.sub.3
AOB + NH.sub.3 Priopionibacterium acnes -114 -19,067 -1.05 ATCC
6919 Staphylococcus aureus (MRSA) -117.6 8.2 2.03 ATCC BAA-1717
Pseudomonas aeruginosa -84.3 2.65 379 ATCC 15442 Streptococcus
pyogenes -965 -2.88 -3.81 ATCC 19615 Acinetobacter baumannii (MDR)
-5.43 92.4 89.8 ATCC BAA-1605
Example 6
Wound Healing
[0679] The effect of Nitrosomonas eutropha D23 (sometimes also
called B244) on wound closure in diabetic mice was evaluated in two
separate studies. In Study 1, db/db mice (8 mice/group) were
pre-treated by body immersion daily for one week with 3
concentrations of D23 (10.sup.7, 10.sup.8 or 10.sup.9 cells/ml)
supplemented with ammonium chloride, or with vehicle control
suspension only. Subsequently, full-thickness wounds generated on
the back of each animal were treated topically once daily for 14
days with vehicle alone or equal volumes of 3 concentrations of D23
(10.sup.7, 10.sup.8 or 10.sup.9 cells/ml) in PBS supplemented
ammonium chloride. Of the three D23-treated groups, the group
receiving the highest dose showed significant improvement in wound
closure from day 5 to day 15, with the most pronounced improvement
of 83% observed on day 9 post-wounding. The median time to 50%
wound closure was significantly reduced (P<0.05) for the animals
treated with 10.sup.9 cells/ml of D23, as compared to the animal
group receiving vehicle treatment alone.
[0680] Initial histopathology analyses of wound tissue samples
collected on Day 15 upon study completion did not reveal any gross
differences between vehicle- and D23-treated animals. Subsequently,
a more in-depth examination of the tissue sections was performed
according to the scoring system and parameters adapted and modified
form Altavilla, et al (2001). This analysis suggested a trend of
increased levels of angiogenesis and maturity of granulation tissue
with decreased levels of dermal inflammation in animals treated
with 10.sup.9 cells/ml of D23 versus the vehicle control group,
which was consistent with the observed improvement in wound healing
rates of the D23-treated animals
[0681] N. eutropha strain D23 was tested for its ability to
accelerate wound healing in a diabetic mouse model, using C57BLKS/J
Iar-+Lepr.sup.db/+Lepr.sup.db male mice (non-GLP). A detailed
protocol is set out below.
Day -6 to Day 1: Whole-Body Immersion Pre-Treatment of Mice with
Test Organism [0682] 1. Mix the 10.times.D23 stock suspension
stored at 4.degree. C. by inverting several times until a
homogenous suspension is obtained. [0683] 2. Pipet 2.times.29 ml of
the 10.times. stock suspension into two 50 ml polypropylene
centrifuge tubes. [0684] 3. Centrifuge at 8,000.times.g for 15 min
at 20.degree. C. [0685] 4. Remove supernatant and any residual
buffer from the pellets and resuspend the two pellets gently but
thoroughly into a total of 58 ml room-temperature Phosphate
Buffered Saline, pH 7.4 (PBS). This is the 10.times.D23 (Test
Organism) suspension to use for the following steps. [0686] 5.
Prepare 500 ml baths containing the Test Organism at 1.times.,
0.1.times. and 0.01.times. strength in pre-warmed PBS at 30.degree.
C. supplemented with 2 mM NH.sub.4Cl, or a Vehicle control bath, as
shown below. Prepare and use one bath at a time from the
10.times.D23 suspension kept at room temperature before continuing
with the next bath. This will prevent keeping the Test Substance at
30.degree. C. for long time periods without ammonium. To prevent
contamination of the Vehicle control group with the Test Substance,
begin with the Vehicle control group before proceeding with the D23
baths. [0687] 6. Immerse each group of mice in corresponding baths
for 60 sec daily for seven days. [0688] 7. Use a fresh 500 ml baths
for each daily immersion into the Test Organism or Vehicle
control.
TABLE-US-00008 [0688] TABLE 8 10.times. D23 1M (room PBS NH.sub.4/
BATH/ temp.) pH 7.4 Cl CFU/ GROUP (ml) (ml) (ml) ml Vehicle -- 500
1.0 0 (control) 1.times. D23 50 450 1.0 109 0.1.times. D23 5 495
1.0 108 0.01.times. D23 0.5 499 1.0 107
Day 1: Wounding of Mice by Skin Puncture
[0689] 1. Generate skin wounds on the back of each mouse by skin
puncture after shaving of the back and shoulders. [0690] 2. House
each mouse separately for the remainder of the study. Day 1 to Day
15: Topical Treatment of Skin Wounds with Test Organism [0691] 1.
Mix the 10.times.D23 stock suspension stored at 4.degree. C. by
inverting several times until a homogenous suspension is obtained.
[0692] 2. Pipet 1 ml of the 10.times. stock suspension into a 1.5
ml polypropylene tube. [0693] 3. Centrifuge at 17,000.times.g for 3
min at room temperature. [0694] 4. Remove supernatant and any
residual buffer from the pellet and resuspend pellet gently but
thoroughly into a total of 10 ml pre-warmed Phosphate Buffered
Saline, pH 7.4 (PBS) at 30.degree. C. This is the 1.times.D23 (Test
Organism) suspension to use for the following steps. [0695] 5.
Prepare 1.times., 0.1.times. and 0.01.times. suspensions of the
Test Organism in pre-warmed PBS supplemented with 2 mM NH.sub.4Cl,
or a Vehicle control solution, in 50 ml polypropylene tubes as
shown below. [0696] 6. Draw 2.0 ml of each suspension using a
repetitive pipet. [0697] 7. Drip slowly 0.2 ml of the Test Organism
(1.times., 0.1.times., 0.01.times. groups), or an equal volume of
Vehicle control, onto each wound and surrounding shaved skin area.
Gently spread applied suspension onto the wound and the entire
shaved skin area using a pipet tip. [0698] 8. Repeat application of
Test Organism or Vehicle control daily for a total of 14 days.
[0699] 9. Measure wound size by wound planimetry and obtain photo
images of each wound on Day 1, 3, 5, 7, 9, 11, 13 and 15 using
Image Analyzer (Image-pro plus version 4.5, Media Cybernetics Inc).
[0700] 10. Calculate % wound closure and wound half-closure time
(CT.sub.50) for each group.
TABLE-US-00009 [0700] TABLE 9 PBS 1M 1.times. D23 pH 7.4 NH.sub.4Cl
CFU/ CFU/ GROUP (ml) (ml) (.mu.l) ml wound Vehicle 5.0 10 0 0
(control) 1.times. D23 5.0 0 10 10.sup.9 2 .times. 10.sup.8
0.1.times. D23 0.5 4.5 10 10.sup.8 2 .times. 10.sup.7 0.01.times.
D23 0.05 4.95 10 10.sup.7 2 .times. 10.sup.6
Day 15 (Upon Study Completion): Collection of Wound Tissues Samples
and Histopathology Analyses
[0701] 1. Obtain half-wound tissue samples from four mice per group
using aseptic technique to avoid cross-contamination of tissues.
[0702] 2. Proceed with histopathology analyses. [0703] 3. Store
temporarily at -70.degree. C. the remainder half-wound samples and
the additional four full-size wound tissues from each group for
further evaluation.
[0704] As shown in FIG. 5A, topical application of 10.sup.9 CFU/ml
of strain D23 significantly (*p<0.05) accelerated wound healing.
The sample size was N=8 animals/gp. The group receiving the highest
doses showed significant improvement in would closure from day 5 to
day 15, with the most pronounced improvement of 83% observed on day
9, post-wounding. This study demonstrates the potential therapeutic
benefit of ammonia oxidizing bacteria, e.g., D23, to diabetic foot
ulcers, chronic wounds, and other related indications.
[0705] FIG. 5B is a plot showing CT.sub.50 versus control (vehicle)
and 10.sup.9 CFU/ml D23. CT50 is the time required to achieve a 50%
wound closure. As shown in the plot, those wounds having
application of D23 provided for lower CT.sub.50 values.
[0706] FIG. 5C is a plot of another experiment in which the
protocol above was carried out to obtain wound closure measurements
versus time. Control (vehicle) wounds were tested and compared to
D23 at 10.sup.9 CFU/ml wounds. This plot shows the effects of D23
when immersion pre-treatment and topical application was carried
out.
[0707] FIG. 5D is a plot of another experiment in which the
protocol above was carried out, without immersion pre-treatment, to
obtain wound closure measurements versus time. Control (vehicle)
wounds were tested and compared to applications of D23 at 10.sup.9
CFU/ml and 10.sup.10 CFU/ml to wounds. This plot shows the effects
of D23 when topical application was carried out.
[0708] FIG. 5E is a plot showing CT.sub.50 versus control (vehicle)
and 10.sup.9 CFU/ml D23, with and without immersion pre-treatment,
and 10.sup.9 CFU/ml D23 without pre-treatment. As shown in the
plot, those wounds having application of D23 provided for lower
CT50 values.
[0709] FIG. 5F are images of the wound healing experiments, at Day
1, Day 11, and Day 15. AOB represents D23.
[0710] Possible modulation of inflammatory responses coupled with
ant-infective action of D23 could prove an effective topical
treatment against diabetic and other chronic wounds.
[0711] FIG. 5G are plots of blood glucose levels in the mice tested
for the control (vehicle) and various concentrations of D23. "IM"
shown in the x-axis of the right-hand panel plot represents those
tests down with an immersion pre-treatment of D23. FIG. 5H is a
plot of body weight of the animals used in testing for the study
including immersion pre-treatment, over the time of the study. FIG.
5I are plots of body weight of the animals used in testing for the
study, including the immersion pre-treatment study, and the study
done without immersion pre-treatment, over the time of the
studies.
[0712] In Study 2, the effect of pretreatment of db/db mice with
10.sup.9 cells/ml of B244 on wound closure was examined. Groups of
seven mice were treated topically with 10.sup.9 cells/ml of B244
with and without prior body immersion. One additional group of
seven mice was treated topically with 10.sup.10 cells/ml of D23
(B244). Corresponding vehicle groups (seven mice) were run in
parallel with and without body immersion as negative controls.
Wound surface area and photo images of each wound were obtained as
before. These studies reproduced the findings of Study 1 suggesting
improvement of wound closure with a B244 dose of approximately
10.sup.9 cells/ml. Moreover, topical treatment alone with 10.sup.9
cells/ml improved wound closure rates similar to the animals
receiving topical treatments with immersion. Additional
histopathology analyses by of H & E--stained wound tissue
sections recovered on Day 5 did not reveal any differences between
vehicle and D23 (B244)-treated wounds.
[0713] Cytokine and growth factor expression in D23-treated
diabetic animals was investigated using Luminex technology.
Specifically, expression of growth-regulated oncogene/keratinocyte
chemoattractant (Gro/KC), interleukin-1 (IL-1), interleukin-6
(IL-6), macrophage inflammatory protein-2 (MIP-2), tumor necrosis
factor (TNF), and vascular endothelial growth factor (VEGF) was
compared between D23-treated and control diabetic animals in serum
samples obtained on Day 5 and Day 15 from four mice per group
treated with or without prior body immersion. In similar Luminex
analyses, lysates of tissues from D23-treated or Vehicle control
animals obtained upon completion of the study (Day 15) were also
analyzed. Abnormally high and sustained expression of inflammation
markers, including MIP-2, TNF.alpha. and IL-1.beta., has been
previously associated with a dysregulated inflammatory response and
impaired wound healing processes in db/db mice (Wetzler, 2000).
Analyses of Day 5 and Day 15 serum samples yielded very low signal
for all six cytokines in both D23-treated and vehicle control
animals, a result indicating the lack of systemic effects following
wound treatment with high D23 doses. In wound tissue lysates
obtained on Day 15, MIP-2 levels (1155-1516 pg/100 g total protein)
were significantly higher than the remaining five cytokines, with
IL-6 and Gro/KC measured at much lower levels (44-48 pg/100 g total
protein) and both IL-1 and VEGF being close to undetectable
(.ltoreq.3.8 pg/100 g total protein). Overall, no difference was
observed between D23-treated animals and vehicle control animals
with or without full-body immersion in D23 suspensions. The levels
of all six cytokines or growth factors measured in tissue lysates
of all four groups of mice examined are summarized in Table 10
below.
TABLE-US-00010 TABLE 10 Cytokine levels measured in wound tissue
lysates of D23-treated and vehicle control-treated db/db mice MIP-2
Gro/KC IL-1.beta. IL-6 (pg/ TNF.alpha. VEGF (pg/100 g (pg/100 g
(pg/100 g 100 g (pg/100 g (pg/100 g Treatment Animal protein)
protein) protein) protein) protein) protein) Vehicle 1-1 49 2.4 78
1089 28.7 5.8 (with prior 1-3 66 2.4 134 1335 31.2 4.5 immersion)
1-5 59 2.7 128 1112 25.7 4.2 1-7 76 1.2 148 1013 9.4 4.1 MEAN 62
2.2 122 1137 23.7 4.7 D23 3-1 49 2.1 66 1830 24.7 4.1 10.sup.9
cells/ml 3-3 75 1.8 162 1615 32.3 3.6 (with prior 3-5 50 2.4 132
1896 23.9 4.3 immersion) 3-7 17 1.5 28 720 9.0 3.4 MEAN 48 1.9 97
1516 22.5 3.8 Vehicle 5-1 43 1.5 90 833 13.2 3.6 (topical 5-3 55
2.2 104 1312 18.6 3.6 only) 5-5 44 1.4 59 644 17.6 3.2 5-7 100 3.8
168 1308 48.6 4.0 MEAN 60 2.2 105 1024 24.5 3.6 D23 6-1 82 2.2 105
1573 28.5 2.9 10.sup.9 cells/ml 6-3 18 0.8 36 943 8.0 2.5 (topical
6-5 25 1.2 45 1027 9.5 2.2 only) 6-7 49 1.5 92 1077 18.5 2.9 MEAN
44 1.4 69 1155 16.1 2.6
[0714] Pharmacokinetic evaluation of D23 (B244) in rodents was
conducted during a 28-day repeat dose toxicology study as described
in the section below. No separate single dose pharmacokinetic
studies were run for D23 (B244).
Example 7
Toxicology
[0715] 28-Day Safety Study of Nitrosomonas eutropha D23 (B244)
Application on Full-Thickness Wounds of Streptozotocin-Induced
Diabetic Sprague-Dawley Rats
[0716] The objectives of this study were to determine the potential
toxicity of Nitrosomonas eutropha D23 (B244) in rats when given
dermally on wounded skin for a minimum of 28 days, and to evaluate
the potential reversibility of any findings. In addition, the
toxicokinetic characteristics of D23 (B244) were determined.
Study Design and Methods
[0717] The design was based on the study objectives, the overall
product development strategy for the test article, and the
following study design guidelines: OECD Guidelines 407 and 417,
Committee for Human Medicinal Products (CHMP), and ICH Harmonised
Tripartite Guidelines M3 (R2), S3a, and S6 (R1). The study design
is outlined herein and results are shown in Table 11.
TABLE-US-00011 TABLE 11 28-Day Safety Study design Dose Volume Dose
No. of Animals Group Test Dose Level (mL/kg) Conc. Main Study
Recovery No. Material (CFU/kg/day) Split (CFU/mL) M F M F 1 Control
0 0.8 0 10 10 5 5 Article 2 AOB-D23- 6 .times. 10.sup.7 0.8 8
.times. 10.sup.7 10 10 0 0 100 3 AOB-D23- 6 .times. 10.sup.8 0.8 8
.times. 10.sup.8 10 10 0 0 100 4 AOB-D23- 6 .times. 10.sup.9 0.8 8
.times. 10.sup.9 10 10 5 5 100 M = Male, F = Female, Conc. =
Concentration, CFU = Colony Forming Unit. Control Article = 99.998%
Phosphate Buffered Saline, pH 7.4 (PBS), 0.002% 1M NH4Cl
[0718] For induction of diabetes, Streptozotocin was administered
to Sprague Dawley rats via intraperitoneal injection on Day -4.
Animals with blood glucose levels of >200 mg/dL were considered
as responders to the Streptozotocin treatment and were used for the
dosing phase of the study. Two full-thickness skin wounds were
created per animal (1 on each side of the back of each anesthetized
animal) using an 8-mm skin biopsy punch. The wounds were left
uncovered during administration of the control and test article and
also for the duration of the study. The test and control articles
were administered to the appropriate animals dermally once daily
(for 24 hours.+-.1 hour) from Days 1 to 28. The end points
evaluated in this study were the following: clinical signs, dermal
findings, body weights, body weight changes, food consumption,
ophthalmology, glucose analysis, clinical pathology parameters
(hematology, coagulation, clinical chemistry, urinalysis,
hemoglobin A1c, and methemoglobulin), C-reactive protein and serum
ferritin analysis, toxicokinetic parameters, gross necropsy
findings, organ weights, and wound histopathology.
Results
[0719] The results for the endpoints evaluated in the 28-day GLP
toxicology study are outlined below in Table 12.
TABLE-US-00012 TABLE 12 28-Day Safety Study-Results End points
Observations Comments Mortality No unscheduled deaths during the
course of the study were attributed to D23 (B244). One control male
was found dead on Day 41; the cause of death due to necrosis in the
kidney, liver, pancreas, and spleen Clinical No test article D23
(B244)-related clinical Similar clinical signs Observations signs
were observed during the study. have been previously Clinical signs
including abdominal associated with an distension, prominent
backbone, fur uncontrolled diabetic staining, soft stools and
ungroomed state in rats and other appearance were related to the
diabetic state animal models of the animals Skin discoloration
(red/black) was present in both control and treated animals Dermal
Scores No dermal irritation occurred during the study No erythema
or edema was observed following dermal administration of the test
article Body Weights and No D23 (B244)-related effects on body Body
Weight weight or body weight change were noted Changes during the
study. Mean weight gain was observed throughout the study interval,
with isolated instances of slight loss in individual animals across
the dose groups which did not follow specific dose-related trends
Food Consumption There were no test article-related effects on food
consumption. Ophthalmic There were no D23 (B244)-related The
appearance of Examinations ophthalmologic changes during the study.
The cataracts is a known majority of the animals on study developed
complication of cataracts and there were no differences among
diabetes dose groups. Hematology, No test article-related changes
were noted in Coagulation, hematology, coagulation, hemoglobin A1c,
Hemoglobin A1c, and methemoglobin parameters on and Methemoglobin
Day 29 or 43. Isolated statistically significant differences were
noted during the study; however, the values were within the
historical control ranges and were not considered meaningful
Clinical Chemistry No test article-related changes were noted on
Days 29 or 43. Isolated statistically significant differences were
noted during the study; however, the values were within the
historical control ranges and not considered meaningful Urinalysis
No test article-related effects C-reactive Protein No test
article-related effects and Serum Ferritin Analysis Gross Pathology
No test article-related gross findings were Any gross findings
noted on Day 29 or Day 43 observed were considered to be related to
the diabetic condition of the rats and incidental in nature Organ
Weights There was an increase in adrenal weight in females at
.gtoreq.6 .times. 10.sup.8 CFU/kg/day on Day 29, whereas adrenal
weight was decreased in males and there were no associated gross
pathology findings making the association of this finding to D23
(B244) administration equivocal Potential D23 (B244)-related organ
weight changes noted at the terminal euthanasia (Day 29) were not
observed at the end of the recovery period (Day 43) Histopathology
No D23 (B244)-related microscopic findings Terminal on Day 29.
Euthanasia (Day 29) Changes observed in the kidneys, large and
small intestine, and urinary bladder were related to the diabetic
state of the animals. The incidence and severity of these findings
were similar in all study groups including controls. Changes at the
administration/wound sites included epidermal regeneration,
fibrosis, and granulomatous inflammation. The incidence and
severity of these findings were similar in all groups including
controls Histopathology Changes observed on Day 43 were similar
Recovery to those reported on Day 29 Euthanasia (Day 43)
Conclusions
[0720] Once daily application of D23 (B244) on rat wounds was well
tolerated at levels of 6.times.10.sup.7, 6.times.10.sup.8, and
6.times.10.sup.9 CFU/kg/day. [0721] No D23 (B244)-related mortality
observed during the study [0722] Healing of full tissue thickness
excisions was similar in all groups [0723] No D23 (B244)-related
clinical signs or dermal irritation were observed [0724] No effects
observed during the study on body weight, food consumption,
clinical pathology parameters, c-reactive protein, or serum
ferritin [0725] No test article-related gross necropsy findings or
histopathologic findings [0726] The no-observed-adverse-effect
level (NOAEL) was determined to be 6.times.10.sup.9 CFU/kg/day
(8.times.10.sup.9 cells/ml) [0727] No specific target organs were
identified
[0728] No D23 related mortality occurred during the study. There
were no D23-related clinical signs or dermal irritation, and there
were no effects on body weight, body weight changes, food
consumption, clinical pathology parameters, C-reactive protein, or
serum ferritin during the study. There were no test article-related
gross necropsy findings or histopathologic findings. Increases in
adrenal weights were noted in the >6.times.10.sup.8 CFU/kg/day
females on Day 29; however, association with D23 was considered
equivocal based on the lack of a similar effect in the males, the
lack of corresponding gross findings, and the lack of microscopic
evaluation of this tissue.
[0729] All wound sites were completely covered by epidermis and
appeared to be in the remodeling/resolution phase, which was
characterized by stratification of the epidermis with
keratinization and refinement of the dermal collagen (synthesis,
bundling, and degradation) and capillaries to restore the normal
architecture of the epidermis and dermis. The incidence and
severity were similar in all groups, including controls.
Example 8
Antibiotic Susceptibility
[0730] The activities of five antibiotics, each representing a
different antibiotic class, were tested against Nitrosomonas
eutropha D23. The antibiotics tested included clindamycin,
erythromycin, gentamicin, piperacillin with or without the
.beta.-lactamase inhibitor Tazobactam, and tetracycline. These were
chosen based on the Clinical and Laboratory Standards Institute
(CLSI) recommendations for routine testing and reporting of
phylogenetically-related proteobacteria (Pseudomonas aeruginosa)
listed under Non-fastidious organisms and Non-Enterobacteriaceae in
the CLSI 24th Informational Supplement (M100-524), and also
included topical or systemic antimicrobial agents commonly used
against acne, such as clindamycin or tetracycline. Studies with
clindamycin were included even though this antibiotic was not
expected to be very effective at inhibiting Nitrosomonas, as is the
case for other aerobic Gram-negative bacteria.
[0731] Minimal Inhibitory Concentrations (MICs) were determined by
culturing N. eutropha D23 in decreasing concentrations of each of
the five antibiotics. Bacterial growth at 30.degree. C. was
monitored for 48-72 hr by determining optical density (OD.sub.600)
values in samples collected at 24 hr intervals. MIC values were
identified as the lowest antibiotic concentration from a two-fold
dilution series leading to no increase in OD.sub.600 measurements
for the 2 or 3-day incubation period. The N. eutropha D23 phenotype
in each antibiotic test was determined as Susceptible,
Intermediate, or Resistant according to the MIC Interpretive
Criteria provided by the CLSI. As summarized in Table 13, these
studies demonstrated susceptibility of N. eutropha D23 to
erythromycin and gentamicin and intermediate resistance to
tetracycline and piperacillin suggesting the lack of strong
antibiotic-resistance potential by the Drug Substance. Clindamycin
resistance observed for N. eutropha D23 is in agreement with
previous reports for natural resistance of aerobic Gram-negative
bacteria to this antibiotic. In addition to testing the
.beta.-lactam antibiotic piperacillin alone, the broad range
.beta.-lactamase inhibitor Tazobactam was also tested in
combination with piperacillin to assess the possible expression of
.beta.-lactamase(s) by N. eutropha D23. The results from this
comparison showed no increase in N. eutropha D23 susceptibility,
indicating the absence of .beta.-lactamase expression by N.
eutropha D23, at least under the conditions tested.
TABLE-US-00013 TABLE 13 MIC values for five antibiotics tested
against N. eutropha D23 cultures in vitro MIC MIC Interpretive
Antibiotic Antibiotic Class (.mu.g/ml) Criteria* Clindamycin
Lincosamide >16 Resistant (.gtoreq.4 .mu.g/ml) Erythromycin
Macrolide 0.16 Susceptible (.ltoreq.0.5 .mu.g/ml) Gentamicin
Aminoglycoside 0.25 Susceptible (.ltoreq.4 .mu.g/ml) Piperacillin
.beta.-lactam 64 Intermediate (32-64 .mu.g/ml) Piperacillin/
.beta.-lactam/ 64/4 Intermediate Tazobactam .beta.-lactamase
(32/4-64/4 .mu.g/ml) inhibitor Tetracycline Tetracycline 8
Intermediate (8 .mu.g/ml) *as recommended by the Clinical and
Laboratory Standards Institute (values in parentheses represent MIC
levels for corresponding Susceptible, Intermediate or Resistant
outcomes)
Conclusions
[0732] These studies demonstrate susceptibility of D23 (B244) to
macrolide and aminoglycoside antibiotics and resistance to
lincosamides, results that indicate the lack of strong
antibiotic-resistance potential by the Drug Substance.
Example 9
Elucidation of Structure of N. eutropha
[0733] N. eutropha was defined at the species and the strain level
using PCR and gene sequencing methodologies. The species level was
defined as N. eutropha by sequencing of the V1-V5 variable regions
of the 16S rRNA gene. N. eutropha was defined as a novel N.
eutropha strain D23 by identification of a unique gene from whole
genome sequence analysis. N. eutropha was defined at the species
level as N. eutropha by 16S rRNA gene sequencing using the MicroSeq
500 rDNA Bacterial Identification PCL and sequencing kit.
[0734] Strain identity may be determined using custom primers,
which correspond to the underlined portions of the following
sequence and the D23 1c1355 sequence & primers Table 14 below.
While not wishing to be bound by theory, it is believed that gene
D23 1c1355 is unique to N. eutropha D23, and thus performing a PCR
amplification reaction within gene D23 1c1355 will indicate whether
N. eutropha D23 is present in a given sample.
TABLE-US-00014 TABLE 14 D23_1c1355 sequence & primers Product
Tm Posi- size Primer Sequence (5'-3') (.degree. C.) tion (bp) D23_
AATCTGTCTCCACAGGCAGC 54 287-305 595 1c1355-F (SEQ ID NO: 64) D23_
TATACCCACCACCCACGCTA 54 881-862 1c1355-R (SEQ ID NO: 65)
TABLE-US-00015 D23_1c1355 outer membrane autotransporter barrel
domain-containing protein (SEQ ID NO: 66)
TTGGTTGGTTTGAAACAGGTAAGGGAGAAGGAGGAAAATCGCCAGAATAT 10 20 30 40 50
CGTCGCCAAAGGTTATCGGATCACCATAGCTTATCCACTCAAAGGGGAGA 60 70 80 90 100
TTATCATGAGCAAGGTTCGTCGATTAAAAAAGAGTTTATATACGGTTACT 110 120 130 140
150 GCACTAACTCTCGGTTTCGGACCATTTGTGACAGCGAGTGGACAATCATT 160 170 180
190 200 CGAAGAAACACCCGTACAAACACCCGGACGAGCTTTTGCAGTGGACAATT 210 220
230 240 250 TAAAGGGTATCTGTGTACAAAACACAAGTGAAGACCCCTCATTAGCAATA 260
270 280 290 300 GCTTGCACCTTCGCACTGGGCGGGATAAATGATATTACCGCGCAGAATCT
310 320 330 340 350
GTCTCCACAGGCAGCGATTCAGGCCGAGTCGATCGCGATTACTTCTCCCT 360 370 380 390
400 ATCAGTTTATTCGCAGCACGAATGAAAGCATACAGCGGCTAACAGGTCGC 410 420 430
440 450 TCTGCTGAGAAACGTCAGCAACAATCCTCTTTTTTACTACAAAGCTCAGC 460 470
480 490 500 GTCGGTAGCAGGCACGCCATCATTTGGCACTTCTGGTTTTATAGGGCCTG 510
520 530 540 550 TAGGGGTTTCGCTGAGCGGTGGCGGGAGCTTTGGTGAACGCAATACCGCT
560 570 580 590 600
GAAGGGCAGACCGGTTTTCAATTGAATACCCGGCAAACCAGCCTGATGAT 610 620 630 640
650 CGATTATTCATTTAATCAAAAATTGATTGGCGGCTTTTCCTTTAATTATC 660 670 680
690 700 TGGGGACAGATCGTAATTTGAGATTGGCGAGTGGGGACTTGAATTCCGAT 710 720
730 740 750 AGCTATCGGTTTGCACCCTTTGTGCTTTTCAGACCAACTACCAATAGCTA 760
770 780 790 800 CTTAACTCTGATGGGAGGGTATGCTTTGGTTAATTATCGTTCCACGCGCA
810 820 830 840 850
GCGTTTCGAGTCAAAATGACATCACGTTTGATAACGCCACAGCCAACTAT 860 870 880 890
900 GATGCTAATCAGTTTTTTGCTAGCGTGGGTGGTGGGTATACCTTTACTTT 910 920 930
940 950 AATGGATGGATGGAATCTGCGAGGATATGGTCGCGGGGACTTTAGTGATA 960 970
980 990 1000 TTAGTATCCAGAGCTTTCAGGAAAAAGGTGGCGTTGCTCATAGTGGGAAC
1010 1020 1030 1040 1050
GATAGTTTATCTCTTGCTATGTCTGTGAATAAACAAACCATACGCTCGGT 1060 1070 1080
1090 1100 TACCAGTACATTAGGCGTTGAACTTAGTCATGCAATTAGCACCAGAACTT 1110
1120 1130 1140 1150
TTATTCCCGTCATTATCCCGAGACTGCGTGCAGAATGGGTGCATGAATTT 1160 1170 1180
1190 1200 GAAAACAATGCCAGAACTATCACGGCCGGTTTCACTGGCCAGAACTATAG 1210
1220 1230 1240 1250
TCCCACTTCTGCATCAATGGCAGTTGCAAGCTCAGTGCGTAATTGGGCAA 1260 1270 1280
1290 1300 ACCTGGGGGTTGGAGTGCAAATGCTGTTTGCCCGCTCGATTATCGGGTAC 1310
1320 1330 1340 1350
ATTAATTACGACAGATTAATTATCAAGCACGCGGAGAACAATATCATTTC 1360 1370 1380
TGGTGGGATTCGTATGAATTTCTAA
Example 10
Administering Ammonia Oxidizing Bacteria to the Back of the Head to
Change the Skin Microbiome
[0735] Ammonia oxidizing bacteria (N. eutropha D23) was applied
topically to the back of the head of a subject for over 2 weeks.
The dose was 3.times.10.sup.10 CFU applied per day. The product
concentration was 1.times.10.sup.9 CFU/ml (15 ml, two times a day)
in a phosphate buffer with magnesium chloride. On each day a skin
swab was taken to isolate and sequence all the bacterial DNA that
was present, using isolation and sequencing protocols known in the
art.
[0736] Ammonia oxidizing bacteria of the genus Nitrosomonas was not
present in the Day 0 sample, and was detected and present in the
Day 7, 14, and 16 skin swabs.
[0737] As shown in FIGS. 17 and 18, which plots the proportion
versus bacterial genus for Day 0, 1, 8, 14, and 16, the application
of ammonia oxidizing bacteria led to proportional increases in
commensal non-pathogenic Staphylococcus (which was at least 98%
Staphylococcus epidermidis) from close to 0% on day 0 to
approximately 50% on day 16. Additionally, application of ammonia
oxidizing bacteria led to a proportional reduction in potentially
pathogenic or disease associated Propionibacteria over the time
period tested (from over 75% on day 0 to less than 50% on day 16).
Application of ammonia oxidizing bacteria also led to reductions in
potentially pathogenic or disease associated Stenotrophomonas over
the time period tested (from 0.1% on day 0 to less than 0.01% on
day 16.)
[0738] Some of the data shown in FIGS. 1 and 2 is also presented
below in Table 15.
TABLE-US-00016 TABLE 15 Genera by Day Proportion Proportion
Proportion by genus: by genus: by genus: Day Propionibacteria
Staphylococci Stenotrophomonas 0 0.78 0.01 0.13 1 0.79 0.1 0 8 0.8
0.15 0 14 0.55 0.45 0.001 16 0.48 0.49 0
[0739] As shown in Table 15, the proportion of Propionibacteria was
reduced after about 14 days (compare data for Day 0, 1, and 8 with
Day 14 and 16 in Table 15). The proportion of Staphylococci
increased after about two weeks (compare data for Day 0, 1, and 8
with Day 14 and 16 in Table 15). The proportion of Stenotrophomonas
decreased after about 1 day (compare data for Day 0 with Day 1, 8,
14, and 16 in Table 15).
[0740] These changes in the skin microbiome composition to a less
pathogenic state indicate that application of ammonia oxidizing
bacteria would be useful in treatment of dermatologic diseases
including but not limited to acne, eczema, skin infections, and
rosacea.
Example 11
Studies with Ammonia-Oxidizing Bacteria for the Human Skin:
Cosmetic Effects, Safety, Detection and Skin Metagenomics
[0741] A blinded, placebo-controlled 24 human volunteer study
randomized 4:1 AOB to placebo control was performed. Subjects
applied a Nitrosomonas suspension (10.sup.9 CFU/ml, 2 times per
day, for a total of 3.times.10.sup.10 CFU per day) to their face
and scalp twice daily for one week and were followed for two
additional weeks post-application. Volunteers were instructed to
refrain from using hair products during the one-week AOB
application as well as the week following application, then
returned to regular shampoo use for the third week. Scalp swabs
were obtained on Day 0 as baseline controls and on Day 1, 3, 8, 14
and 21 to assess presence/absence of AOB by PCR and 16S rRNA
sequencing analyses.
[0742] No serious adverse events were associated with AOB
application for one week and the product was deemed safe. AOB users
reported a clear improvement in skin condition and quality, as
indicated by self-assessment reports completed after the seven-day
application period. Using AOB-specific PCR analyses of the skin
samples, we could demonstrate presence of the bacteria in 83-100%
of AOB users during the application period, whereas no AOB were
detected in the placebo control samples. All subjects lacked AOB
from baseline swabs obtained prior to study initiation, consistent
with the predicted sensitivity of these bacteria to soaps and other
commercial products. Amplification of the 16S rRNA gene and
sequencing of a subset of samples confirmed presence of AOB in
corresponding samples and suggested potential trends in modulating
the skin microbiome by topical AOB application. In summary, live
AOB-based products are safe and could hold great promise as novel
self-regulating topical delivery agents of nitrite and nitric oxide
to the human skin.
[0743] As shown in Table 16, below, the proportion of Nitrosomonas
(AOB) went up when comparing Day 0 versus Day 8. The proportion of
other bacteria, Propionibacterium, Enterobacter, and Citrobacter
went down, when comparing Day 0 versus Day 8. The p-values
indicated in Table 16 demonstrate that the most significant change
between Day 0 and Day 8 was observed with Nitrosomonas (AOB)
followed by Propionibacterium. Enterobacter and Citrobacter also
showed changes between Day 0 and Day 8 to a lesser degree.
TABLE-US-00017 TABLE 16 Trends in microbiome composition following
AOB application (Day 0 versus Day 8) Genus P-value (unadjusted)
Trend Nitrosomonas (AOB) 0.0039 Up Propionibacterium 0.0078 Down
Enterobacter 0.0346 Down Citrobacter 0.036 Down
[0744] Because nitrite and nitric oxide have been implicated in
critical physiological functions, such as vasodilation, skin
inflammation and wound healing, we have hypothesized that AOB may
have beneficial effects on both healthy and immunopathological skin
conditions by metabolizing ammonia from sweat while concurrently
driving skin acidification. We reasoned that Nitrosomonas would be
safe for human use because they are slow-growing and incapable of
utilizing organic carbon sources, they are sensitive to
antibiotics, and they have never been linked to animal or human
disease. Here we describe a blinded, placebo-controlled 24 human
volunteer study where subjects applied a live Nitrosomonas
suspension to their face and scalp twice daily for one week and
were subsequently followed for two additional weeks. Volunteers did
not use hair products during the first and second week, then they
returned to their regular routine for the third week. Scalp swabs
were obtained on Day 0 as baseline controls and on Day 1, 3, 8, 14
and 21 to assess presence/absence of Nitrosomonas and to examine
microbial diversity. Importantly, no adverse events were associated
with topical application. PCR analyses demonstrated presence of the
bacteria in 83%-100% of skin swabs obtained from AOB users during
or immediately after completion of the one-week application period
(Day 1, 3 or 8) and in 60% of the users on Day 14, but not in any
of the placebo control samples. All subjects lacked AOB from
baseline swabs obtained prior to study initiation. Increased levels
of AOB during the one-week application period correlated with a
qualitative improvement in skin condition, in contrast to no
improvement reported by placebo control subjects. Sequencing of the
16S rRNA gene amplification product obtained from a subset of
subjects verified the presence of AOB in corresponding samples and
suggested potential modulation of the skin microbiome composition.
In summary, live Nitrosomonas are well tolerated and may hold
promise as novel self-regulating topical delivery agents of nitrite
and nitric oxide to the human skin.
[0745] Here, we present the results from preliminary studies in
humans where we have begun evaluating topical application of a
Nitrosomonas suspension to the human skin and the potential of
using AOB as natural delivery systems of NO/NO.sub.2.sup.- in vivo.
We have explored methodologies for AOB detection in skin specimens
and the possible effects of AOB in skin microbial communities, as
well as collected important user feedback from the early adopters
of our topical cosmetic.
[0746] Methods
[0747] Culture Conditions.
[0748] N. eutropha D23 was propagated in batch culture at
28-30.degree. C. in mineral salt medium supplemented with 20-50 mM
NH.sub.4.sup.+ and sodium carbonate as the carbon source [Ensign et
al, 1993]. For continuous culture, D23 was grown at .about.10.sup.9
cells/ml in a 1 liter mini-Bioreactor (Applikon Biotechnology) at
28.degree. C. using sodium carbonate for both pH neutralization and
the carbon source.
[0749] Nitrite Quantification.
[0750] Nitrite concentrations in culture supernatants were
determined using the Griess colorimetric assay [Hageman and
Kucklesby, 1971] and sodium nitrite as standards.
[0751] DNA Extraction from Skin Swabs.
[0752] Samples were maintained in 1 ml of 10% AssayAssure
Bioservative (Thermo Scientific) diluted in PBS. Biomass was
centrifuged and cells were lysed using a method developed for skin
specimens [Grice, 2009] with modifications to the buffer designed
to maintain long DNA integrity. DNA was then purified using the
PowerLyzer UltraClean microbial DNA isolation kit (Mo Bio
Laboratories). N. eutropha D23 was identified using a 3-gene PCR
signature amplifying the ammonia monooxygenase encoding locus
amoCAB.
[0753] PCR and Library Preparation.
[0754] Full-length 16S rRNA genes were amplified in duplicate
reactions using a cocktail of primers and AccuPrime DNA polymerase
SuperMix kit (Life Technologies). All PCR products were directly
treated with the SMRTbell Template Prep Kit followed by the
DNA/Polymerase Binding Kit P4 (Pacific Biosciences).
[0755] 16S rDNA Sequencing and Analysis.
[0756] PCR products were sequenced using the Pacific Biosciences RS
instrument [Eid, 2009]. Raw base calls were transformed to
consensus DNA sequences using the Pacific Biosciences Consensus
Tools package and then processed with the Whole Biome Microbiome
Profiling Platform to obtain phylum-genus and strain-level
frequency measures for each sample.
[0757] Human Volunteer Study.
[0758] A total of 24 male volunteers were included in a blinded,
placebo-controlled, study each for a total of three weeks according
to a protocol for topical AOB-001 use approved by the Allendale
Institutional Review Board (Old Lyme, Conn.). Written informed
consent was obtained from each study participant. Subjects applied
15 ml of an aqueous suspension of N. eutropha (AOB-001), or placebo
(vehicle), twice daily containing .about.10.sup.9 cells/ml.
[0759] The human volunteer study design for the preliminary
evaluation of a Nitrosomonas-containing topical suspension
(AOB-001) is shown in FIG. 5K. Detection of AOB was performed by
PCR in scalp swab samples. FIG. 5L shows PCR analyses of scalp
swabs collected during the study. The left panel indicates the
percent-positive samples for AOB-specific three-gene signature
(amoA, amoB, amoC). The right panel indicates the Composite PCR
scores for a total of six samples collected from each of 23
volunteers. The scoring scheme used for the positive samples
collected at each of six sampling points is indicated.
[0760] Skin microbiome composition prior and during AOB-001
application were obtained by 16S rDNA sequencing. FIG. 5M indicates
that genus-level bacterial diversity as determined by 16S rDNA
sequencing in skin swab samples collected before and after topical
application of AOB-001.
[0761] The percentage of the total sequence reads representing each
of twelve bacterial genera in samples collected at baseline prior
to application (Day 0) and immediately after the one week
application (Day 8), or one week after stopping topical application
(Day 14), are shown.
[0762] FIG. 5N indicates changes in abundance of Nitrosomonas and
other species in skin samples collected before and after AOB-001
application. Panel A shows percentages of the total 16S rDNA
sequence reads representing Nitrosomonas prior to application (Day
0), immediately after the one-week application (Day 8), or one week
after terminating application (Day 14) are shown. Panel B shows a
change in patterns in abundance of species detected by 16S rDNA
sequencing in Day 0 versus Day 8 samples collected from AOB
users.
[0763] AOB-001 users report an improvement in skin condition. FIG.
5O shows a user evaluation of AOB-001. Assessment of AOB-001
cosmetic effects was provided by 23 volunteers upon completion of
the one week application to their scalp and face. Subjects were
plotted in order of increasing composite PCR scores. (The responses
were categorized as 2=agree strongly; 0=no change; -2=disagree
strongly). In summary, AOB-001 is well-tolerated. The user
responses in a blind study indicate improved skin/scalp condition.
AOB (Nitrosomonas) are readily detectable in skin microbiome
samples by PCR and 16S rRNA gene sequencing. Preliminary microbiome
analyses indicate modulation of skin microbiota by AOB.
TABLE-US-00018 SUPPLEMENTARY TABLE 1 Annotation of genes in SEQ ID
NO: 1. Feature Length D23 C91 ID Type Start Stop Frame Strand (bp)
Function Subsystem Gbkld Alias fig|6666666.60966.peg.1 CDS 35 1414
2 + 1380 Chromosomal Cell Division Subsystem D23_1c0001 Neut_0001
replication initiator including YidCD; protein DnaA <br>DNA
replication cluster 1 fig|6666666.60966.peg.2 CDS 1619 2740 2 +
1122 DNA polymerase III beta Cell Division Subsystem D23_1c0002
Neut_0002 subunit (EC 2.7.7.7) including YidCD; <br>DNA
replication cluster 1 fig|6666666.60966.peg.3 CDS 2798 5227 2 +
2430 DNA gyrase subunit B Cell Division Subsystem D23_1c0003
Neut_0003 (EC 5.99.1.3) including YidCD; <br>DNA gyrase
subunits; <br>DNA replication cluster 1; <br>DNA
topoisomerases, Type II, ATP-dependent; <br>Resistance to
fluoroquinolones fig|6666666.60966.peg.4 CDS 5248 5691 1 + 444
FIG039061: -none- D23_1c0004 Neut_0004 hypothetical protein related
to heme utilization fig|6666666.60966.peg.5 CDS 5748 6479 3 + 732
tRNA pseudouridine Colicin V and Bacteriocin D23_1c0005 Neut_0005
synthase A (EC 4.2.1.70) Production Cluster; <br>RNA
pseudouridine syntheses; <br>tRNA modification Bacteria;
<br>tRNA processing fig|6666666.60966.peg.6 CDS 7261 7518 1 +
258 4Fe--4S ferredoxin, iron- Inorganic Sulfur D23_1c0009 Neut_0127
sulfur binding Assimilation fig|6666666.60966.peg.7 CDS 7584 7946 3
+ 363 FIG00858425: -none- D23_1c0010 Neut_0128 hypothetical protein
fig|6666666.60966.peg.8 CDS 11430 7966 -3 - 3465
Transcription-repair Transcription factors D23_1c0011 Neut_0129
coupling factor bacterial; <br>Transcription repair cluster
fig|6666666.60966.peg.9 CDS 12737 11457 -2 - 1281 InterPro
IPR003416 -none- D23_1c0012 Neut_0130 COGs COG3174
fig|6666666.60966.peg.10 CDS 14499 12730 -3 - 1770
Single-stranded-DNA- DNA Repair Base D23_1c0013 Neut_0131 specific
exonuclease Excision RecJ (EC 3.1.--.--) fig|6666666.60966.peg.11
CDS 15277 14681 -1 - 597 InterPro IPR000345 -none- D23_1c0014
Neut_0132 fig|6666666.60966.peg.12 CDS 16285 15365 -1 - 921
Indole-3-glycerol Chorismate: D23_1c0015 Neut_0133 phosphate
synthase (EC Intermediate for 4.1.1.48) synthesis of Tryptophan,
PAPA antibiotics, PABA, 3-hydroxyanthranilate and more.;
<br>Tryptophan synthesis fig|6666666.60966.peg.13 CDS 17321
16296 -2 - 1026 Anthranilate Auxin biosynthesis; D23_1c0016
Neut_0134 phosphoribosyltransferase <br>Chorismate: (EC
2.4.2.18) Intermediate for synthesis of Tryptophan, PAPA
antibiotics, PABA, 3-hydroxyanthranilate and more.;
<br>Tryptophan synthesis fig|6666666.60966.peg.14 CDS 17920
17318 -1 - 603 Anthranilate synthase, Chorismate: D23_1c0017
Neut_0135 amidotransferase Intermediate for component (EC synthesis
of Tryptophan, 4.1.3.27) PAPA antibiotics, PABA,
3-hydroxyanthranilate and more.; <br>Tryptophan synthesis
fig|6666666.60966.peg.15 CDS 18046 19545 1 + 1500 Putative
sensor-like -none- D23_1c0018 Neut_0136 histidine kinase YfhK
fig|6666666.60966.peg.16 CDS 19644 20081 3 + 438 FIG00858754:
-none- D23_1c0019 Neut_0137 hypothetical protein
fig|6666666.60966.peg.17 CDS 20101 21465 1 + 1365 Putative sensory
-none- D23_1c0020 Neut_0138 histidine kinase YfhA
fig|6666666.60966.peg.18 CDS 22742 21474 -2 - 1269 PDZ/DHR/GLGF
domain -none- D23_1c0021 Neut_0139 protein fig|6666666.60966.peg.19
CDS 26700 22798 -3 - 3903 Phosphoribosylformylglycinamidine De Novo
Purine D23_1c0022 Neut_0140 synthase, Biosynthesis; <br>De
synthetase subunit (EC Novo Purine 6.3.5.3)/ Biosynthesis
Phosphoribosylformylglycinamidine synthase, glutamine
amidotransferase subunit (EC 6.3.5.3) fig|6666666.60966.peg.20 CDS
26942 28510 2 + 1569 hypothetical protein -none- D23_1c0023
Neut_0141 fig|6666666.60966.peg.22 CDS 28682 28867 2 + 186
hypothetical protein -none- D23_1c0024 NA fig|6666666.60966.peg.23
CDS 29060 28851 -2 - 210 Death on curing Phd-Doc, YdcE-YdcD
D23_1c0025 NA protein, Doc toxin toxin-antitoxin (programmed cell
death) systems fig|6666666.60966.peg.24 CDS 29367 29227 -3 - 141
Prevent host death Phd-Doc, YdcE-YdcD D23_1c0026 Neut_0143 protein,
Phd antitoxin toxin-antitoxin (programmed cell death) systems
fig|6666666.60966.peg.25 CDS 29726 30082 2 + 357 blr1219;
hypothetical -none- D23_1c0028 Neut_0144 protein
fig|6666666.60966.peg.26 CDS 30113 31672 2 + 1560 NAD(P)HX
epimerase/ YjeE; <br>YjeE D23_1c0029 Neut_0145 NAD(P)HX
dehydratase fig|6666666.60966.peg.29 CDS 31959 32078 3 + 120
hypothetical protein -none- D23_1c0030 NA fig|6666666.60966.peg.30
CDS 32096 32914 2 + 819 O-antigen export -none- D23_1c0031
Neut_0146 system permease protein RfbD fig|6666666.60966.peg.31 CDS
33063 33266 3 + 204 hypothetical protein -none- D23_1c0032
Neut_0147 fig|6666666.60966.peg.32 CDS 33441 33995 3 + 555
hypothetical protein -none- D23_1c0033 Neut_0148
fig|6666666.60966.peg.33 CDS 34044 34424 3 + 381 hypothetical
protein -none- D23_1c0034 NA fig|6666666.60966.peg.34 CDS 34530
35588 3 + 1059 putative transposase -none- D23_1c0035 Neut_0149
fig|6666666.60966.peg.36 CDS 36348 36064 -3 - 285 HigA protein
(antitoxin Toxin-antitoxin replicon D23_1c0037 Neut_0150 to HigB)
stabilization systems fig|6666666.60966.peg.37 CDS 36621 36379 -3 -
243 HigB toxin protein Toxin-antitoxin replicon D23_1c0038
Neut_0151 stabilization systems fig|6666666.60966.peg.38 CDS 36580
36750 1 + 171 hypothetical protein -none- D23_1c0039 NA
fig|6666666.60966.peg.39 CDS 36747 38108 3 + 1362 Teichoic acid
export Rhamnose containing D23_1c0040 Neut_0152 ATP-binding protein
glycans TagH (EC 3.6.3.40) fig|6666666.60966.peg.40 CDS 38105 42433
2 + 4329 Glycosyl transferase, -none- D23_1c0041 Neut_0153 group 2
family protein fig|6666666.60966.peg.41 CDS 42537 43733 3 + 1197
glycosyl transferase, -none- D23_1c0042 NA group 1/2 family protein
fig|6666666.60966.peg.42 CDS 43945 44838 1 + 894 Alpha-L-Rha
alpha-1,3- Rhamnose containing D23_1c0043 Neut_0166
L-rhamnosyltransferase glycans (EC 2.4.1.--)
fig|6666666.60966.peg.43 CDS 45457 45140 -1 - 318 HigA protein
(antitoxin Toxin-antitoxin replicon D23_1c0044 Neut_0167 to HigB)
stabilization systems fig|6666666.60966.peg.44 CDS 45610 45470 -1 -
141 HigB toxin protein Toxin-antitoxin replicon D23_1c0045
Neut_0168 stabilization systems fig|6666666.60966.peg.45 CDS 45950
46279 2 + 330 Glycosyl transferase, -none- D23_1c0046 Neut_0169
group 2 family protein fig|6666666.60966.peg.47 CDS 47082 46804 -3
- 279 hypothetical protein -none- D23_1c0047 NA
fig|6666666.60966.peg.49 CDS 48719 47757 -2 - 963 Mobile element
protein -none- D23_1c0049 Neut_0978 fig|6666666.60966.peg.50 CDS
48899 48777 -2 - 123 Mobile element protein -none- D23_1c0050
Neut_0357 fig|6666666.60966.peg.51 CDS 49218 48970 -3 - 249 Mobile
element protein -none- D23_1c0051 Neut_2405
fig|6666666.60966.peg.52 CDS 49615 49502 -1 - 114 hypothetical
protein -none- D23_1c0052 NA fig|6666666.60966.peg.53 CDS 49842
50255 3 + 414 Nucleotidyltransferase -none- D23_1c0053 Neut_0172
(EC 2.7.7.--) fig|6666666.60966.peg.54 CDS 50257 50622 1 + 366
Nucleotidyltransferase -none- D23_1c0054 Neut_0173 (EC 2.7.7.--)
fig|6666666.60966.peg.55 CDS 51293 50880 -2 - 414 Mobile element
protein -none- D23_1c0056 NA fig|6666666.60966.peg.56 CDS 51432
51253 -3 - 180 hypothetical protein -none- D23_1c0057 Neut_0176
fig|6666666.60966.peg.57 CDS 51530 52492 2 + 963 Mobile element
protein -none- D23_1c0058 Neut_1746 fig|6666666.60966.peg.58 CDS
52657 52908 1 + 252 Mobile element protein -none- D23_1c0059
Neut_0884 fig|6666666.60966.peg.59 CDS 52964 53326 2 + 363 Mobile
element protein -none- D23_1c0060 Neut_2499
fig|6666666.60966.peg.60 CDS 54452 53361 -2 - 1092 putative
transposase -none- D23_1c0061 Neut_0177 fig|6666666.60966.peg.61
CDS 54765 54430 -3 - 336 FIG00859125: -none- D23_1c0062 Neut_0178
hypothetical protein fig|6666666.60966.peg.62 CDS 55016 55774 2 +
759 dTDP-Rha:A-D-GlcNAc- dTDP-rhamnose D23_1c0063 Neut_0179
diphosphoryl synthesis polyprenol, A-3-L- rhamnosyl transferase
WbbL fig|6666666.60966.peg.63 CDS 56735 55788 -2 - 948 UDP-glucose
4- CBSS- D23_1c0064 Neut_0180 epimerase (EC 5.1.3.2)
296591.1.peg.2330; <br>N-linked Glycosylation in Bacteria;
<br>Rhamnose containing glycans fig|6666666.60966.peg.64 CDS
56874 56746 -3 - 129 hypothetical protein -none- D23_1c0065 NA
fig|6666666.60966.peg.65 CDS 60470 57075 -2 - 3396 Adenylate
cyclase (EC cAMP signaling in D23_1c0066 Neut_0181
4.6.1.1)/Guanylate bacteria cyclase (EC 4.6.1.2)
fig|6666666.60966.peg.66 CDS 60633 60755 3 + 123 hypothetical
protein -none- D23_1c0067 NA fig|6666666.60966.peg.67 CDS 62853
60769 -3 - 2085 Ubiquinone Ubiquinone D23_1c0068 Neut_0182
biosynthesis Biosynthesis; monooxygenase UbiB <br>Ubiquinone
Biosynthesis-gjo fig|6666666.60966.peg.68 CDS 63084 63821 3 + 738
hypothetical protein -none- D23_1c0069 Neut_0183
fig|6666666.60966.peg.69 CDS 64515 66023 3 + 1509 CBSS- -none-
D23_1c0070 NA 498211.3.peg.1514: hypothetical protein
fig|6666666.60966.peg.70 CDS 66074 66751 2 + 678 FIG039767: -none-
D23_1c0071 NA hypothetical protein fig|6666666.60966.peg.71 CDS
66741 70157 3 + 3417 FIG007317: -none- D23_1c0072 NA hypothetical
protein fig|6666666.60966.peg.72 CDS 70190 71326 2 + 1137
FIG005429: -none- D23_1c0073 Neut_0184 hypothetical protein
fig|6666666.60966.peg.73 CDS 71379 71939 3 + 561 Lipid carrier:
UDP-N- CBSS- D23_1c0074 Neut_0185 acetylgalactosaminyltransferase
296591.1.peg.2330;
(EC 2.4.1.--) <br>N-linked Glycosylation in Bacteria
fig|6666666.60966.peg.74 CDS 71949 73931 3 + 1983
Nucleoside-diphosphate CBSS-296591.1.peg.2330 D23_1c0075 Neut_0186
sugar epimerase/dehydratase fig|6666666.60966.peg.75 CDS 74467
73949 -1 - 519 cytidine and -none- D23_1c0076 Neut_0187
deoxycytidylate deaminase family protein fig|6666666.60966.peg.76
CDS 74956 74594 -1 - 363 Mobile element protein -none- D23_1c0077
Neut_2499 fig|6666666.60966.peg.77 CDS 75263 75012 -2 - 252 Mobile
element protein -none- D23_1c0078 Neut_0884
fig|6666666.60966.peg.78 CDS 75586 76446 1 + 861 Flagellar motor
rotation Flagellar motility; D23_1c0079 Neut_0188 protein MotA
<br>Flagellum fig|6666666.60966.peg.79 CDS 76489 77433 1 +
945 Flagellar motor rotation Flagellar motility; D23_1c0080
Neut_0189 protein MotB <br>Flagellum fig|6666666.60966.peg.80
CDS 77408 78205 2 + 798 FIG00858624: -none- D23_1c0081 Neut_0190
hypothetical protein fig|6666666.60966.peg.81 CDS 79621 78218 -1 -
1404 Cysteinyl-tRNA Zinc regulated enzymes; D23_1c0082 Neut_0191
synthetase (EC 6.1.1.16) <br>tRNA aminoacylation, Cys
fig|6666666.60966.peg.83 CDS 79830 80384 3 + 555 Peptidyl-prolyl
cis-trans Peptidyl-prolyl cis-trans D23_1c0083 Neut_0192 isomerase
PpiB (EC isomerase; 5.2.1.8) <br>Queuosine- Archaeosine
Biosynthesis fig|6666666.60966.peg.84 CDS 80403 80894 3 + 492
Peptidyl-prolyl cis-trans Peptidyl-prolyl cis-trans D23_1c0084
Neut_0193 isomerase PpiB (EC isomerase; 5.2.1.8)
<br>Queuosine- Archaeosine Biosynthesis
fig|6666666.60966.peg.85 CDS 80972 81424 2 + 453 Rhodanese-related
-none- D23_1c0085 Neut_0194 sulfurtransferase
fig|6666666.60966.peg.86 CDS 82260 81439 -3 - 822 Undecaprenyl-
-none- D23_1c0086 Neut_0195 diphosphatase (EC 3.6.1.27)
fig|6666666.60966.peg.87 CDS 84206 82308 -2 - 1899 Thiamin
biosynthesis Thiamin biosynthesis D23_1c0087 Neut_0196 protein ThiC
fig|6666666.60966.peg.88 CDS 84412 85068 1 + 657
Protein-L-isoaspartate Protein-L-isoaspartate O- D23_1c0088
Neut_0197 O-methyltransferase methyltransferase; (EC 2.1.1.77)
<br>Stationary phase repair cluster; <br>Ton and Tol
transport systems fig|6666666.60966.peg.90 CDS 85216 86493 1 + 1278
Type I secretion outer Multidrug Resistance D23_1c0089 Neut_0198
membrane protein, Efflux Pumps; <br>Ton TolC precursor and
Tol transport systems fig|6666666.60966.peg.91 CDS 89009 86556 -2 -
2454 ATP-dependent Proteasome bacterial; D23_1c0090 Neut_0199
protease La (EC <br>Proteolysis in 3.4.21.53) Type II
bacteria, ATP-dependent fig|6666666.60966.peg.92 CDS 89253 89375 3
+ 123 hypothetical protein -none- D23_1c0091 NA
fig|6666666.60966.peg.93 CDS 89433 89579 3 + 147 hypothetical
protein -none- D23_1c0092 NA fig|6666666.60966.peg.94 CDS 90769
89555 -1 - 1215 Serine--pyruvate Photorespiration D23_1c0093
Neut_0200 aminotransferase (EC (oxidative C2 cycle); 2.6.1.51)/L-
<br>Pyruvate Alanine alanine:glyoxylate Serine
Interconversions aminotransferase (EC 2.6.1.44)
fig|6666666.60966.peg.95 CDS 93514 91088 -1 - 2427 ATP-dependent
Proteasome bacterial; D23_1c0095 Neut_0201 protease La (EC
<br>Proteolysis in 3.4.21.53) Type I bacteria, ATP-dependent
fig|6666666.60966.peg.96 CDS 94903 93620 -1 - 1284 ATP-dependent
Clp Proteasome bacterial; D23_1c0096 Neut_0202 protease ATP-binding
<br>Proteolysis in subunit ClpX bacteria, ATP-dependent
fig|6666666.60966.peg.97 CDS 95607 94963 -3 - 645 ATP-dependent Clp
Proteasome bacterial; D23_1c0097 Neut_0203 protease proteolytic
<br>Proteolysis in subunit (EC 3.4.21.92) bacteria, ATP-
dependent; <br>cAMP signaling in bacteria
fig|6666666.60966.peg.98 CDS 96907 95591 -1 - 1317 Cell division
trigger Bacterial Cell Division D23_1c0098 Neut_0204 factor (EC
5.2.1.8) fig|6666666.60966.peg.99 CDS 97996 97241 -1 - 756
Short-chain Transcription repair D23_1c0100 Neut_0205
dehydrogenase/reductase cluster SDR fig|6666666.60966.peg.100 CDS
99750 98107 -3 - 1644 Heat shock protein 60 GroEL GroES D23_1c0101
Neut_0206 family chaperone GroEL fig|6666666.60966.peg.101 CDS
100080 99790 -3 - 291 Heat shock protein 60 GroEL GroES D23_1c0102
Neut_0207 family co-chaperone GroES fig|6666666.60966.peg.102 CDS
100244 101554 2 + 1311 Adenosylmethionine-8- Biotin biosynthesis;
D23_1c0103 Neut_0208 amino-7-oxononanoate <br>Biotin
biosynthesis aminotransferase (EC Experimental; <br>Biotin
2.6.1.62) synthesis cluster fig|6666666.60966.peg.103 CDS 101561
102967 2 + 1407 Metallo-beta-lactamase Bacterial RNA- D23_1c0104
Neut_0209 family protein, RNA- metabolizing Zn- specific dependent
hydrolases; <br>Ribonucleases in Bacillus
fig|6666666.60966.peg.104 CDS 103374 103066 -3 - 309 Cytochrome c,
class I -none- D23_1c0105 Neut_0210 fig|6666666.60966.peg.105 CDS
103536 104300 3 + 765 Exodeoxyribonuclease DNA repair, bacterial
D23_1c0106 Neut_0211 III (EC 3.1.11.2) fig|6666666.60966.peg.106
CDS 104347 105459 1 + 1113 Alanine dehydrogenase Pyruvate Alanine
Serine D23_1c0107 Neut_0212 (EC 1.4.1.1) Interconversions
fig|6666666.60966.peg.107 CDS 106118 105597 -2 - 522 Conserved
Tolerance to colicin E2 D23_1c0108 Neut_0213 uncharacterized
protein CreA fig|6666666.60966.peg.109 CDS 107425 106253 -1 - 1173
Permeases of the major -none- D23_1c0109 Neut_0214 facilitator
superfamily fig|6666666.60966.peg.110 CDS 108032 107454 -2 - 579
Uncharacterized protein -none- D23_1c0110 Neut_0215 family UPF0016
fig|6666666.60966.peg.112 CDS 108821 109603 2 + 783
Ribulose-5-phosphate -none- D23_1c0113 Neut_0218 4-epimerase and
related epimerases and aldolases fig|6666666.60966.peg.113 CDS
109609 113274 1 + 3666 InterPro -none- D23_1c0114 Neut_0219
IPR000014:IPR001789:IPR002106: IPR002570:IPR003594: IPR003660:
IPR003661:IPR004358:IPR005467 COGs COG0642
fig|6666666.60966.peg.114 CDS 113292 114485 3 + 1194 Succinyl-CoA
ligase TCA Cycle D23_1c0115 Neut_0220 [ADP-forming] beta chain (EC
6.2.1.5) fig|6666666.60966.peg.115 CDS 114489 115364 3 + 876
Succinyl-CoA ligase TCA Cycle D23_1c0116 Neut_0221 [ADP-forming]
alpha chain (EC 6.2.1.5) fig|6666666.60966.peg.116 CDS 115402
115722 1 + 321 FIG00858523: -none- D23_1c0117 Neut_0222
hypothetical protein fig|6666666.60966.peg.117 CDS 115750 117177 1
+ 1428 D-alanyl-D-alanine CBSS-84588.1.peg.1247; D23_1c0118
Neut_0223 carboxypeptidase (EC <br>Metallocarboxypeptidases
3.4.16.4) (EC 3.4.17.--); <br>Murein Hydrolases;
<br>Peptidoglycan Biosynthesis fig|6666666.60966.peg.118 CDS
117265 118227 1 + 963 Mobile element protein -none- D23_1c0119
Neut_1278 fig|6666666.60966.peg.119 CDS 120193 120056 -1 - 138
hypothetical protein -none- D23_1c0120 NA fig|6666666.60966.rna.5
RNA 118725 120255 3 + 1531 Small Subunit Ribosomal RNA; -none-
D23_1c0120 ssuRNA; SSU rRNA fig|6666666.60966.peg.121 CDS 122376
122495 3 + 120 hypothetical protein -none- D23_1c0124 NA
fig|6666666.60966.peg.120 CDS 121863 121994 3 + 132 hypothetical
protein -none- D23_1c0124 NA fig|6666666.60966.rna.8 RNA 120652
123535 1 + 2884 Large Subunit -none- D23_1c0124 Ribosomal RNA;
IsuRNA; LSU rRNA fig|6666666.60966.rna.9 RNA 123600 123716 3 + 117
5S RNA -none- D23_1c0126 fig|6666666.60966.peg.123 CDS 124878
124708 -3 - 171 hypothetical protein -none- D23_1c0127 NA
fig|6666666.60966.peg.124 CDS 125317 125496 1 + 180 hypothetical
protein -none- D23_1c0129 Neut_0547 fig|6666666.60966.peg.125 CDS
125792 126799 2 + 1008 NAD-dependent CBSS-296591.1.peg.2330
D23_1c0130 Neut_0225 epimerase/dehydratase
fig|6666666.60966.peg.126 CDS 126808 128082 1 + 1275 UDP-glucose
-none- D23_1c0131 Neut_0226 dehydrogenase (EC 1.1.1.22)
fig|6666666.60966.peg.127 CDS 128985 128089 -3 - 897 Permeases of
the -none- D23_1c0132 Neut_0227 drug/metabolite transporter (DMT)
superfamily fig|6666666.60966.peg.128 CDS 129078 130283 3 + 1206
N-succinyl-L,L- Lysine Biosynthesis DAP D23_1c0133 Neut_0228
diaminopimelate Pathway, GJO scratch aminotransferase alternative
(EC 2.6.1.17) fig|6666666.60966.peg.129 CDS 130311 131132 3 + 822
2,3,4,5- Lysine Biosynthesis DAP D23_1c0134 Neut_0229
tetrahydropyridine-2,6- Pathway, GJO scratch dicarboxylate N-
succinyltransferase (EC 2.3.1.117) fig|6666666.60966.peg.130 CDS
131322 131693 3 + 372 FIG00858507: -none- D23_1c0135 Neut_0230
hypothetical protein fig|6666666.60966.peg.131 CDS 131801 132127 2
+ 327 FIG00858507: -none- D23_1c0136 Neut_0231 hypothetical protein
fig|6666666.60966.peg.132 CDS 132190 132312 1 + 123 hypothetical
protein -none- D23_1c0137 NA fig|6666666.60966.peg.133 CDS 132314
133303 2 + 990 Biotin operon repressor/ Biotin biosynthesis;
D23_1c0138 Neut_0232 Biotin-protein ligase <br>Biotin
biosynthesis; (EC 6.3.4.15) <br>Biotin synthesis cluster;
<br>Biotin synthesis cluster fig|6666666.60966.peg.134 CDS
133331 134104 2 + 774 Pantothenate kinase Coenzyme A D23_1c0139
Neut_0233 type III, CoaX-like (EC Biosynthesis; 2.7.1.33)
<br>Coenzyme A Biosynthesis cluster fig|6666666.60966.peg.135
CDS 134123 134794 2 + 672 GTP-binding protein Universal GTPases
D23_1c0140 Neut_0234 EngB fig|6666666.60966.peg.136 CDS 134938
135945 1 + 1008 Porphobilinogen Heme and Siroheme D23_1c0141
Neut_0235 synthase (EC 4.2.1.24) Biosynthesis; <br>Zinc
regulated enzymes fig|6666666.60966.peg.137 CDS 136861 136064 -1 -
798 Phosphate transport High affinity phosphate D23_1c0142
Neut_0236 ATP-binding protein transporter and control PstB (TC
3.A.1.7.1) of PHO regulon; <br>Phosphate metabolism
fig|6666666.60966.peg.138 CDS 137797 136871 -1 - 927 Phosphate
transport High affinity phosphate D23_1c0143 Neut_0237 system
permease transporter and control protein PstA (TC of PHO regulon;
3.A.1.7.1) <br>Phosphate metabolism fig|6666666.60966.peg.139
CDS 138817 137876 -1 - 942 Phosphate transport High affinity
phosphate D23_1c0144 Neut_0238 system permease transporter and
control protein PstC (TC of PHO regulon;
3.A.1.7.1) <br>Phosphate metabolism fig|6666666.60966.peg.140
CDS 139048 139299 1 + 252 FIG00858998: -none- D23_1c0146 Neut_0239
hypothetical protein fig|6666666.60966.peg.141 CDS 140580 139432 -3
- 1149 Cell division protein Bacterial Cell Division; D23_1c0147
Neut_0240 FtsZ (EC 3.4.24.--) <br>Bacterial Cytoskeleton;
<br>cell division cluster containing FtsQ; <br>cell
division core of larger cluster fig|6666666.60966.peg.142 CDS
141909 140650 -3 - 1260 Cell division protein Bacterial Cell
Division; D23_1c0149 Neut_0241 FtsA <br>Bacterial
Cytoskeleton; <br>cell division cluster containing FtsQ;
<br>cell division core of larger cluster
fig|6666666.60966.peg.143 CDS 142678 141950 -1 - 729 Cell division
protein Bacterial Cell Division; D23_1c0150 Neut_0242 FtsQ
<br>Bacterial Cytoskeleton; <br>cell division cluster
containing FtsQ; <br>cell division core of larger cluster
fig|6666666.60966.peg.144 CDS 143654 142734 -2 - 921
D-alanine--D-alanine Peptidoglycan D23_1c0152 Neut_0243 ligase (EC
6.3.2.4) Biosynthesis; <br>Peptidoglycan biosynthesis--gjo;
<br>cell division cluster containing FtsQ
fig|6666666.60966.peg.145 CDS 144649 143651 -1 - 999 UDP-N-
Peptidoglycan D23_1c0153 Neut_0244 acetylenolpyruvoylglucosamine
Biosynthesis; <br>UDP- reductase (EC N-acetylmuramate from
1.1.1.158) Fructose-6-phosphate Biosynthesis
fig|6666666.60966.peg.146 CDS 146080 144659 -1 - 1422 UDP-N-
Peptidoglycan D23_1c0154 Neut_0245 acetylmuramate-- Biosynthesis;
alanine ligase (EC <br>Peptidoglycan 6.3.2.8)
biosynthesis--gjo; <br>cell division cluster containing FtsQ
fig|6666666.60966.peg.147 CDS 147159 146077 -3 - 1083 UDP-N-
Peptidoglycan D23_1c0155 Neut_0246 acetylglucosamine--N-
Biosynthesis; <br>cell acetylmuramyl- division core of larger
(pentapeptide) cluster pyrophosphoryl- undecaprenol N-
acetylglucosamine transferase (EC 2.4.1.227)
fig|6666666.60966.peg.148 CDS 148372 147212 -1 - 1161 Cell division
protein Bacterial Cell Division; D23_1c0156 Neut_0247 FtsW
<br>Bacterial Cytoskeleton; <br>cell division cluster
containing FtsQ fig|6666666.60966.peg.149 CDS 149789 148377 -2 -
1413 UDP-N- Peptidoglycan D23_1c0157 Neut_0248
acetylmuramoylalanine-- Biosynthesis; D-glutamate ligase (EC
<br>Peptidoglycan 6.3.2.9) biosynthesis--gjo
fig|6666666.60966.peg.150 CDS 150871 149786 -1 - 1086 Phospho-N-
Peptidoglycan D23_1c0158 Neut_0249 acetylmuramoyl- Biosynthesis
pentapeptide- transferase (EC 2.7.8.13) fig|6666666.60966.peg.151
CDS 152316 150943 -3 - 1374 UDP-N- Peptidoglycan D23_1c0159
Neut_0250 acetylmuramoylalanyl- Biosynthesis; D-glutamyl-2,6-
<br>Peptidoglycan diaminopimelate--D- biosynthesis--gjo
alanyl-D-alanine ligase (EC 6.3.2.10) fig|6666666.60966.peg.152 CDS
153875 152313 -2 - 1563 UDP-N- Peptidoglycan D23_1c0160 Neut_0251
acetylmuramoylalanyl- Biosynthesis; D-glutamate--2,6-
<br>Peptidoglycan diaminopimelate ligase biosynthesis--gjo
(EC 6.3.2.13) fig|6666666.60966.peg.153 CDS 155545 153872 -1 - 1674
Cell division protein Ftsl 16S rRNA modification D23_1c0161
Neut_0252 [Peptidoglycan within P site of synthetase] (EC ribosome;
<br>Bacterial 2.4.1.129) Cell Division; <br>Bacterial
Cytoskeleton; <br>CBSS- 83331.1.peg.3039; <br>Flagellum
in Campylobacter; <br>Peptidoglycan Biosynthesis
fig|6666666.60966.peg.155 CDS 155895 155608 -3 - 288 Cell division
protein FtsL 16S rRNA modification D23_1c0162 Neut_0253 within P
site of ribosome; <br>Bacterial Cell Division;
<br>Bacterial Cytoskeleton; <br>Stationary phase repair
cluster fig|6666666.60966.peg.156 CDS 156845 155892 -2 - 954 rRNA
small subunit 16S rRNA modification D23_1c0163 Neut_0254
methyltransferase H within P site of ribosome; <br>Bacterial
Cell Division fig|6666666.60966.peg.157 CDS 157094 156861 -2 - 234
Cell division protein 16S rRNA modification D23_1c0164 Neut_0255
MraZ within P site of ribosome; <br>Bacterial Cell Division;
<br>Bacterial Cytoskeleton fig|6666666.60966.peg.158 CDS
157584 157859 3 + 276 DNA-3-methyladenine DNA Repair Base
D23_1c0165 NA glycosylase II (EC Excision 3.2.2.21)
fig|6666666.60966.peg.159 CDS 158202 158420 3 + 219 Rho-specific
inhibitor of Transcription factors D23_1c0166 Neut_0257
transcription bacterial termination (YaeO)
fig|6666666.60966.peg.160 CDS 159328 158561 -1 - 768 InterPro
IPR001173 -none- D23_1c0167 Neut_0258 COGs COG0463
fig|6666666.60966.peg.161 CDS 159475 159924 1 + 450 InterPro
IPR000086 -none- D23_1c0168 Neut_0259 COGs COG0494
fig|6666666.60966.peg.162 CDS 160257 160814 3 + 558 possible
(U92432) ORF4 -none- D23_1c0169 Neut_0260 [Nitrosospira sp. NpAV]
fig|6666666.60966.peg.164 CDS 160969 161451 1 + 483 FIG00859298:
-none- D23_1c0170 Neut_0261 hypothetical protein
fig|6666666.60966.peg.165 CDS 161593 162063 1 + 471 Adenine Purine
conversions; D23_1c0171 Neut_0262 phosphoribosyltransferase
<br>cAMP signaling in (EC 2.4.2.7) bacteria
fig|6666666.60966.peg.166 CDS 162260 163573 2 + 1314 Seryl-tRNA
synthetase CBSS- D23_1c0172 Neut_0263 (EC 6.1.1.11)
326442.4.peg.1852; <br>Glycine and Serine Utilization;
<br>tRNA aminoacylation, Ser fig|6666666.60966.peg.167 CDS
163620 164306 3 + 687 FIG00858527: -none- D23_1c0173 Neut_0264
hypothetical protein fig|6666666.60966.peg.168 CDS 165061 164351 -1
- 711 Phosphoglycerate Glycolysis and D23_1c0174 Neut_0265 mutase
(EC 5.4.2.1) Gluconeogenesis; <br>Phosphoglycerate mutase
protein family fig|6666666.60966.peg.169 CDS 166178 165111 -2 -
1068 InterPro IPR001225 -none- D23_1c0175 Neut_0266
fig|6666666.60966.peg.170 CDS 166643 166200 -2 - 444 FIG00858776:
-none- D23_1c0176 Neut_0267 hypothetical protein
fig|6666666.60966.peg.171 CDS 167465 166659 -2 - 807
CTP:Inositol-1- -none- D23_1c0177 Neut_0268 phosphate
cytidylyltransferase (2.7.7.--) fig|6666666.60966.peg.172 CDS
168669 167509 -3 - 1161 Cysteine desulfurase Alanine biosynthesis;
D23_1c0178 Neut_0269 (EC 2.8.1.7) <br>CBSS- 84588.1.peg.1247;
<br>mnm5U34 biosynthesis bacteria; <br>tRNA
modification Bacteria fig|6666666.60966.peg.174 CDS 169251 169631 3
+ 381 FIG048548: ATP -none- D23_1c0180 Neut_0270 synthase protein
I2 fig|6666666.60966.peg.175 CDS 169720 170472 1 + 753 ATP synthase
A chain -none- D23_1c0181 Neut_0271 (EC 3.6.3.14)
fig|6666666.60966.peg.176 CDS 170516 170788 2 + 273 ATP synthase C
chain -none- D23_1c0182 Neut_0272 (EC 3.6.3.14)
fig|6666666.60966.peg.177 CDS 170900 171301 2 + 402 ATP synthase B
chain -none- D23_1c0183 Neut_0273 (EC 3.6.3.14)
fig|6666666.60966.peg.178 CDS 171302 171838 2 + 537 ATP synthase
delta -none- D23_1c0184 Neut_0274 chain (EC 3.6.3.14)
fig|6666666.60966.peg.179 CDS 171851 173392 2 + 1542 ATP synthase
alpha -none- D23_1c0185 Neut_0275 chain (EC 3.6.3.14)
fig|6666666.60966.peg.180 CDS 173396 174280 2 + 885 ATP synthase
gamma -none- D23_1c0186 Neut_0276 chain (EC 3.6.3.14)
fig|6666666.60966.peg.181 CDS 174311 175693 2 + 1383 ATP synthase
beta chain -none- D23_1c0187 Neut_0277 (EC 3.6.3.14)
fig|6666666.60966.peg.182 CDS 175842 176141 3 + 300 ATP synthase
epsilon -none- D23_1c0188 Neut_0278 chain (EC 3.6.3.14)
fig|6666666.60966.peg.183 CDS 176389 177765 1 + 1377
N-acetylglucosamine-1- Peptidoglycan D23_1c0189 Neut_0279 phosphate
Biosynthesis; uridyltransferase (EC <br>Peptidoglycan
2.7.7.23)/ Biosynthesis; <br>Sialic Glucosamine-1- Acid
Metabolism; phosphate N- <br>Sialic Acid acetyltransferase
(EC Metabolism; 2.3.1.157) <br>Transcription repair cluster;
<br>Transcription repair cluster; <br>UDP-N-
acetylmuramate from Fructose-6-phosphate Biosynthesis;
<br>UDP- N-acetylmuramate from Fructose-6-phosphate
Biosynthesis fig|6666666.60966.peg.184 CDS 177805 179652 1 + 1848
Glucosamine-fructose- Sialic Acid Metabolism; D23_1c0190 Neut_0280
6-phosphate <br>UDP-N- aminotransferase acetylmuramate from
[isomerizing] (EC Fructose-6-phosphate 2.6.1.16) Biosynthesis
fig|6666666.60966.peg.185 CDS 179795 180520 2 + 726 FIG000859:
Riboflavin, FMN and FAD D23_1c0191 Neut_0281 hypothetical protein
metabolism in plants; YebC <br>RuvABC plus a hypothetical
fig|6666666.60966.peg.186 CDS 180523 181059 1 + 537 Crossover
junction RuvABC plus a D23_1c0192 Neut_0282 endodeoxyribonuclease
hypothetical RuvC (EC 3.1.22.4) fig|6666666.60966.peg.187 CDS
181056 181640 3 + 585 Holliday junction DNA RuvABC plus a
D23_1c0193 Neut_0283 helicase RuvA hypothetical
fig|6666666.60966.peg.188 CDS 181659 182699 3 + 1041 Holliday
junction DNA RuvABC plus a D23_1c0194 Neut_0284 helicase RuvB
hypothetical fig|6666666.60966.peg.189 CDS 182760 183173 3 + 414
4-hydroxybenzoyl-CoA Ton and Tol transport D23_1c0195 Neut_0285
thioesterase family systems active site fig|6666666.60966.peg.190
CDS 183166 183870 1 + 705 MotA/TolQ/ExbB Ton and Tol transport
D23_1c0196 Neut_0286 proton channel family systems
protein fig|6666666.60966.peg.191 CDS 183867 184283 3 + 417 Tol
biopolymer Ton and Tol transport D23_1c0197 Neut_0287 transport
system, TolR systems protein fig|6666666.60966.peg.192 CDS 184304
185200 2 + 897 TolA protein Ton and Tol transport D23_1c0198
Neut_0288 systems fig|6666666.60966.peg.193 CDS 185239 186510 1 +
1272 tolB protein precursor, Ton and Tol transport D23_1c0199
Neut_0289 periplasmic protein systems involved in the tonb-
independent uptake of group A colicins fig|6666666.60966.peg.194
CDS 186565 187086 1 + 522 18K peptidoglycan- Ton and Tol transport
D23_1c0200 Neut_0290 associated outer systems membrane lipoprotein;
Peptidoglycan- associated lipoprotein precursor; Outer membrane
protein P6; OmpA/MotB precursor fig|6666666.60966.peg.195 CDS
187086 187907 3 + 822 TPR repeat containing Ton and Tol transport
D23_1c0201 Neut_0291 exported protein; systems Putative periplasmic
protein contains a protein prenylyltransferase domain
fig|6666666.60966.peg.196 CDS 188060 188644 2 + 585 Queuosine
Biosynthesis Queuosine-Archaeosine D23_1c0202 Neut_0292 QueE
Radical SAM Biosynthesis; <br>tRNA modification Bacteria
fig|6666666.60966.peg.197 CDS 188666 189346 2 + 681 Queuosine
Biosynthesis Queuosine-Archaeosine D23_1c0203 Neut_0293 QueC ATPase
Biosynthesis; <br>tRNA modification Bacteria
fig|6666666.60966.peg.198 CDS 189700 189347 -1 - 354
Dihydroneopterin Folate Biosynthesis D23_1c0204 Neut_0294 aldolase
(EC 4.1.2.25) fig|6666666.60966.peg.199 CDS 189786 190388 3 + 603
Acyl- Glycerolipid and D23_1c0205 Neut_0295 phosphate:glycerol-3-
Glycerophospholipid phosphate O- Metabolism in Bacteria
acyltransferase PlsY fig|6666666.60966.peg.200 CDS 191422 190406 -1
- 1017 TsaD/Kae1/Qri7 Bacterial RNA- D23_1c0206 Neut_0296 protein,
required for metabolizing Zn- threonylcarbamoyladenosine dependent
hydrolases; t(6)A37 formation <br>Macromolecular in tRNA
synthesis operon; <br>YgjD and YeaZ fig|6666666.60966.peg.201
CDS 191698 191910 1 + 213 SSU ribosomal protein Macromolecular
D23_1c0207 Neut_0297 S21p synthesis operon
fig|6666666.60966.peg.202 CDS 191984 192391 2 + 408 Transamidase
GatB Macromolecular D23_1c0208 Neut_0298 domain protein synthesis
operon fig|6666666.60966.peg.203 CDS 192486 194279 3 + 1794 DNA
primase (EC 2.7.7.--) CBSS- D23_1c0209 Neut_0299 349161.4.peg.2417;
<br>Macromolecular synthesis operon fig|6666666.60966.peg.204
CDS 194461 196710 1 + 2250 RNA polymerase sigma CBSS- D23_1c0210
Neut_0300 factor RpoD 349161.4.peg.2417; <br>Flagellum;
<br>Macromolecular synthesis operon; <br>Transcription
initiation, bacterial sigma factors fig|6666666.60966.peg.206 CDS
197605 197180 -1 - 426 Mobile element protein -none- D23_1c0212
Neut_0357 fig|6666666.60966.peg.207 CDS 198088 198819 1 + 732
Mobile element protein -none- D23_1c0213 NA
fig|6666666.60966.peg.209 CDS 200235 199564 -3 - 672 transposase
and -none- D23_1c0214 Neut_2192 inactivated derivatives
fig|6666666.60966.peg.210 CDS 200398 200210 -1 - 189 hypothetical
protein -none- D23_1c0215 NA fig|6666666.60966.peg.211 CDS 200852
200995 2 + 144 Mobile element protein -none- D23_1c0216 Neut_0978
fig|6666666.60966.peg.212 CDS 201848 200970 -2 - 879 Mobile element
protein -none- D23_1c0217 Neut_1720 fig|6666666.60966.peg.213 CDS
202240 201947 -1 - 294 Mobile element protein -none- D23_1c0218
Neut_1719 fig|6666666.60966.peg.214 CDS 202367 203209 2 + 843
Mobile element protein -none- D23_1c0219 Neut_1524
fig|6666666.60966.peg.215 CDS 203592 203461 -3 - 132 Phage Rha
protein -none- D23_1c0220 NA fig|6666666.60966.peg.216 CDS 203906
203571 -2 - 336 Mobile element protein -none- D23_1c0221 Neut_2450
fig|6666666.60966.peg.218 CDS 204442 204113 -1 - 330 hypothetical
protein -none- D23_1c0222 Neut_2449 fig|6666666.60966.peg.219 CDS
205381 204746 -1 - 636 Cytochrome c4 Soluble cytochromes D23_1c0223
Neut_0305 and functionally related electron carriers
fig|6666666.60966.peg.220 CDS 205494 206096 3 + 603 FIG00859469:
-none- D23_1c0224 Neut_0306 hypothetical protein
fig|6666666.60966.peg.221 CDS 206204 207016 2 + 813 Methionine
CBSS- D23_1c0225 Neut_0307 aminopeptidase (EC 312309.3.peg.1965;
3.4.11.18) <br>Translation termination factors bacterial
fig|6666666.60966.peg.222 CDS 207076 207840 1 + 765 Ribonuclease PH
(EC Heat shock dnaK gene D23_1c0226 Neut_0308 2.7.7.56) cluster
extended; <br>tRNA processing fig|6666666.60966.peg.223 CDS
207825 208439 3 + 615 Xanthosine/inosine CBSS-630.2.peg.3360;
D23_1c0227 Neut_0309 triphosphate <br>Heat shock dnaK
pyrophosphatase; gene cluster extended HAM1-like protein
fig|6666666.60966.peg.224 CDS 208474 209709 1 + 1236 Radical SAM
family CBSS-630.2.peg.3360; D23_1c0228 Neut_0310 enzyme, similar to
<br>Heat shock dnaK coproporphyrinogen III gene cluster
extended; oxidase, oxygen- <br>Heme and Siroheme independent,
clustered Biosynthesis; with nucleoside- <br>Queuosine-
triphosphatase RdgB Archaeosine Biosynthesis
fig|6666666.60966.peg.225 CDS 209741 211540 2 + 1800 Multicopper
oxidase Copper homeostasis D23_1c0229 Neut_0311
fig|6666666.60966.peg.226 CDS 211537 212352 1 + 816 Copper
resistance Copper homeostasis D23_1c0230 Neut_0312 protein B
fig|6666666.60966.peg.227 CDS 213327 212398 -3 - 930 hypothetical
protein -none- D23_1c0231 Neut_0313 fig|6666666.60966.peg.228 CDS
213918 213340 -3 - 579 LemA PROTEIN -none- D23_1c0232 Neut_1392
fig|6666666.60966.peg.229 CDS 214368 214553 3 + 186 Mobile element
protein -none- D23_1c0233 Neut_2500 fig|6666666.60966.peg.230 CDS
214610 215206 2 + 597 Mobile element protein -none- D23_1c0234
Neut_1375 fig|6666666.60966.peg.231 CDS 215510 215623 2 + 114
hypothetical protein -none- D23_1c0235 NA fig|6666666.60966.peg.232
CDS 215668 215847 1 + 180 hypothetical protein -none- D23_1c0236
Neut_0314 fig|6666666.60966.peg.233 CDS 217943 216069 -2 - 1875
Glutathione-regulated Glutathione-regulated D23_1c0237 Neut_0315
potassium-efflux system potassium-efflux system ATP-binding protein
and associated functions; <br>Potassium homeostasis
fig|6666666.60966.peg.234 CDS 218233 219195 1 + 963 Mobile element
protein -none- D23_1c0238 Neut_1862 fig|6666666.60966.peg.235 CDS
219960 219271 -3 - 690 InterPro IPR001687 -none- D23_1c0239 NA
fig|6666666.60966.peg.236 CDS 220560 222266 3 + 1707
Glutathione-regulated Glutathione-regulated D23_1c0241 Neut_0318
potassium-efflux system potassium-efflux system protein KefB and
associated functions fig|6666666.60966.peg.237 CDS 222848 223903 2
+ 1056 SAM-dependent -none- D23_1c0242 Neut_0320 methyltransferase
SCO3452 (UbiE paralog) fig|6666666.60966.peg.238 CDS 223971 224243
3 + 273 Phosphate transport High affinity phosphate D23_1c0244
Neut_0321 system permease transporter and control protein PstA (TC
of PHO regulon; 3.A.1.7.1) <br>Phosphate metabolism
fig|6666666.60966.peg.239 CDS 225095 224421 -2 - 675 tRNA
(guanine46-N7-)- RNA methylation; D23_1c0245 Neut_0322
methyltransferase (EC <br>tRNA modification 2.1.1.33)
Bacteria fig|6666666.60966.peg.240 CDS 225934 225128 -1 - 807
Thiazole biosynthesis Thiamin biosynthesis D23_1c0246 Neut_0323
protein ThiG fig|6666666.60966.peg.241 CDS 226194 225994 -3 - 201
Sulfur carrier protein Thiamin biosynthesis D23_1c0247 Neut_0324
ThiS fig|6666666.60966.peg.242 CDS 226421 227008 2 + 588 FIG008443:
CBSS-208964.1.peg.1768 D23_1c0249 Neut_0325 hypothetical protein
fig|6666666.60966.peg.243 CDS 227005 228537 1 + 1533 FIG139976:
CBSS-208964.1.peg.1768 D23_1c0250 Neut_0326 hypothetical protein
fig|6666666.60966.peg.244 CDS 228587 229492 2 + 906 FIG002781:
Alpha-L- CBSS-208964.1.peg.1768 D23_1c0251 Neut_0327 glutamate
ligase family protein fig|6666666.60966.peg.245 CDS 231155 229677
-2 - 1479 Cardiolipin synthetase Cardiolipin synthesis; D23_1c0252
Neut_0328 (EC 2.7.8.--) <br>Glycerolipid and
Glycerophospholipid Metabolism in Bacteria
fig|6666666.60966.peg.246 CDS 231229 231411 1 + 183 hypothetical
protein -none- D23_1c0253 NA fig|6666666.60966.peg.248 CDS 232352
231813 -2 - 540 Urea channel Urel Urea decomposition D23_1c0255
Neut_0329 fig|6666666.60966.peg.249 CDS 232767 232585 -3 - 183
hypothetical protein -none- D23_1c0256 NA fig|6666666.60966.peg.251
CDS 233588 234748 2 + 1161 FIG00855934: -none- D23_1c0259 Neut_0331
hypothetical protein fig|6666666.60966.peg.252 CDS 235271 234831 -2
- 441 Mobile element protein -none- D23_1c0260 Neut_0332
fig|6666666.60966.peg.253 CDS 235792 235397 -1 - 396 NAD-dependent
Calvin-Benson cycle; D23_1c0261 Neut_0333 glyceraldehyde-3-
<br>Glycolysis and phosphate Gluconeogenesis; dehydrogenase
(EC <br>Pyridoxin (Vitamin 1.2.1.12) B6) Biosynthesis
fig|6666666.60966.peg.254 CDS 235832 236260 2 + 429 hypothetical
protein -none- D23_1c0261 Neut_0333 fig|6666666.60966.peg.255 CDS
237167 236592 -2 - 576 Flagellar basal-body P- Flagellum D23_1c0262
Neut_0334 ring formation protein FlgA fig|6666666.60966.peg.256 CDS
237299 237415 2 + 117 hypothetical protein -none- D23_1c0264 NA
fig|6666666.60966.peg.257 CDS 237436 237924 1 + 489 Flagellar
basal-body rod Flagellum; <br>Flagellum D23_1c0265 Neut_0335
protein FlgB in Campylobacter fig|6666666.60966.peg.258 CDS 237930
238334 3 + 405 Flagellar basal-body rod Flagellum;
<br>Flagellum D23_1c0266 Neut_0336 protein FlgC in
Campylobacter fig|6666666.60966.peg.259 CDS 238347 239021 3 + 675
Flagellar basal-body rod Flagellar motility; D23_1c0267 Neut_0337
modification protein <br>Flagellum FlgD
fig|6666666.60966.peg.260 CDS 239037 240296 3 + 1260 Flagellar hook
protein Flagellum D23_1c0268 Neut_0338 FlgE
fig|6666666.60966.peg.261 CDS 240337 241080 1 + 744 Flagellar
basal-body rod Flagellum D23_1c0269 Neut_0339 protein FlgF
fig|6666666.60966.peg.262 CDS 241119 241901 3 + 783 Flagellar
basal-body rod Flagellum D23_1c0270 Neut_0340 protein FlgG
fig|6666666.60966.peg.263 CDS 242034 242828 3 + 795 Flagellar
L-ring protein Flagellar motility; D23_1c0271 Neut_0341 FlgH
<br>Flagellum fig|6666666.60966.peg.264 CDS 242850 243977 3 +
1128 Flagellar P-ring protein Flagellum D23_1c0272 Neut_0342 FlgI
fig|6666666.60966.peg.265 CDS 243991 244998 1 + 1008 Flagellar
protein FlgJ Flagellum D23_1c0273 Neut_0343 [peptidoglycan
hydrolase] (EC 3.2.1.--) fig|6666666.60966.peg.266 CDS 245257
246660 1 + 1404 Flagellar hook- Flagellum D23_1c0274 Neut_0344
associated protein FlgK fig|6666666.60966.peg.267 CDS 246638 247588
2 + 951 Flagellar hook- Flagellum D23_1c0275 Neut_0345 associated
protein FlgL fig|6666666.60966.peg.268 CDS 247665 248210 3 + 546
FIG00859049: -none- D23_1c0276 Neut_0346 hypothetical protein
fig|6666666.60966.peg.269 CDS 249330 248200 -3 - 1131 FIG00859091:
-none- D23_1c0277 Neut_0347 hypothetical protein
fig|6666666.60966.peg.270 CDS 249439 249960 1 + 522 FIG00859511:
-none- D23_1c0278 Neut_0348 hypothetical protein
fig|6666666.60966.peg.271 CDS 249932 250513 2 + 582 GCN5-related N-
-none- D23_1c0279 Neut_0349 acetyltransferase
fig|6666666.60966.peg.272 CDS 250589 250861 2 + 273 FIG001341:
Probable Heat shock dnaK gene D23_1c0280 Neut_0350
Fe(2+)-trafficking cluster extended protein YggX
fig|6666666.60966.peg.273 CDS 250912 253038 1 + 2127 Polyphosphate
kinase High affinity phosphate D23_1c0281 Neut_0351 (EC 2.7.4.1)
transporter and control of PHO regulon; <br>Phosphate
metabolism; <br>Polyphosphate; <br>Purine conversions
fig|6666666.60966.peg.274 CDS 254786 253059 -2 - 1728 Sulfate
permease Cysteine Biosynthesis D23_1c0282 Neut_0352
fig|6666666.60966.peg.275 CDS 255133 254783 -1 - 351
Transcriptional -none- D23_1c0283 Neut_0353 regulator, ArsR family
fig|6666666.60966.peg.277 CDS 256153 255827 -1 - 327 hypothetical
protein -none- D23_1c0285 Neut_0355 fig|6666666.60966.peg.278 CDS
256608 257603 3 + 996 hypothetical protein -none- D23_1c0286
Neut_0356 fig|6666666.60966.peg.279 CDS 258986 257739 -2 - 1248
Mobile element protein -none- D23_1c0287 Neut_0357
fig|6666666.60966.peg.280 CDS 259004 259126 2 + 123 patatin family
protein -none- D23_1c0288 Neut_1317 fig|6666666.60966.peg.281 CDS
259254 259123 -3 - 132 cAMP-binding proteins- cAMP signaling in
D23_1c0289 NA catabolite gene bacteria activator and regulatory
subunit of cAMP- dependent protein kinases
fig|6666666.60966.peg.282 CDS 259543 260031 1 + 489 Cytochrome c'
-none- D23_1c0291 NA fig|6666666.60966.peg.283 CDS 260060 260947 2
+ 888 Putative diheme Soluble cytochromes D23_1c0292 Neut_1381
cytochrome c-553 and functionally related electron carriers
fig|6666666.60966.peg.285 CDS 261917 261708 -2 - 210 hypothetical
protein -none- D23_1c0294 Neut_0363 fig|6666666.60966.peg.288 CDS
262640 262440 -2 - 201 Mobile element protein -none- D23_1c0296
Neut_1696 fig|6666666.60966.peg.289 CDS 263106 264041 3 + 936
hypothetical protein -none- D23_1c0297 NA fig|6666666.60966.peg.290
CDS 264137 265633 2 + 1497 SII1503 protein -none- D23_1c0298 NA
fig|6666666.60966.peg.294 CDS 266897 266760 -2 - 138 hypothetical
protein -none- D23_1c0300 NA fig|6666666.60966.peg.295 CDS 267026
267370 2 + 345 COGs COG3339 -none- D23_1c0301 Neut_0371
fig|6666666.60966.peg.297 CDS 268862 267765 -2 - 1098 L-lactate
Lactate utilization; D23_1c0302 Neut_0372 dehydrogenase (EC
<br>Respiratory 1.1.2.3) dehydrogenases 1
fig|6666666.60966.peg.298 CDS 269655 268972 -3 - 684 Iron-uptake
factor PiuC -none- D23_1c0303 Neut_0373 fig|6666666.60966.peg.299
CDS 271893 269683 -3 - 2211 TonB-dependent Ton and Tol transport
D23_1c0304 Neut_0374 siderophore receptor systems
fig|6666666.60966.peg.301 CDS 272682 273740 3 + 1059 protein of
unknown -none- D23_1c0306 Neut_0377 function DUF81
fig|6666666.60966.peg.302 CDS 273758 274108 2 + 351 hypothetical
protein -none- D23_1c0307 NA fig|6666666.60966.peg.303 CDS 274775
274182 -2 - 594 InterPro IPR001226 -none- D23_1c0308 Neut_0379 COGs
COG0790 fig|6666666.60966.peg.304 CDS 274944 274792 -3 - 153
hypothetical protein -none- D23_1c0309 NA fig|6666666.60966.peg.305
CDS 276110 274986 -2 - 1125 dNTP Purine conversions; D23_1c0310
Neut_0380 triphosphohydrolase, <br>dNTP broad substrate
triphosphohydrolase specificity, subgroup 2 protein family
fig|6666666.60966.peg.306 CDS 277212 276103 -3 - 1110
3-dehydroquinate Chorismate Synthesis; D23_1c0311 Neut_0381
synthase (EC 4.2.3.4) <br>Common Pathway For Synthesis of
Aromatic Compounds (DAHP synthase to chorismate)
fig|6666666.60966.peg.308 CDS 277726 277896 1 + 171 hypothetical
protein -none- D23_1c0312 Neut_0382 fig|6666666.60966.peg.307 CDS
277692 277261 -3 - 432 Shikimate kinase I (EC Chorismate Synthesis;
D23_1c0312 Neut_0382 2.7.1.71) <br>Common Pathway For
Synthesis of Aromatic Compounds (DAHP synthase to chorismate)
fig|6666666.60966.peg.309 CDS 279343 277982 -1 - 1362 Putative
protease -none- D23_1c0313 Neut_0383 fig|6666666.60966.peg.310 CDS
279362 282934 2 + 3573 DNA polymerase III Phage replication
D23_1c0314 Neut_0384 alpha subunit (EC 2.7.7.7)
fig|6666666.60966.peg.311 CDS 283139 282948 -2 - 192 putative
-none- D23_1c0315 Neut_0385 transmembrane protein
fig|6666666.60966.peg.312 CDS 283290 284243 3 + 954 tRNA tRNA
modification D23_1c0316 Neut_0386 dimethylallyltransferase
Bacteria; <br>tRNA (EC 2.5.1.75) processing
fig|6666666.60966.peg.313 CDS 284258 284401 2 + 144 hypothetical
protein -none- D23_1c0317 NA fig|6666666.60966.peg.314 CDS 286041
284776 -3 - 1266 Two component, -none- D23_1c0320 Neut_0387 sigma54
specific, transcriptional regulator, Fis family
fig|6666666.60966.peg.315 CDS 286328 286191 -2 - 138 hypothetical
protein -none- D23_1c0321 NA fig|6666666.60966.peg.316 CDS 288462
286330 -3 - 2133 Nitrogen regulation Possible RNA D23_1c0322
Neut_0388 protein NtrY (EC 2.7.3.--) degradation cluster
fig|6666666.60966.peg.317 CDS 289077 288514 -3 - 564 Probable
proline rich -none- D23_1c0323 Neut_0389 signal peptide protein
fig|6666666.60966.peg.318 CDS 290401 289121 -1 - 1281 16S rRNA RNA
methylation D23_1c0324 Neut_0390 (cytosine(967)-C(5))-
methyltransferase (EC 2.1.1.176) ## SSU rRNA m5C967
fig|6666666.60966.peg.319 CDS 291388 290414 -1 - 975 Methionyl-tRNA
Translation initiation D23_1c0325 Neut_0391 formyltransferase (EC
factors bacterial 2.1.2.9) fig|6666666.60966.peg.320 CDS 291933
291427 -3 - 507 Peptide deformylase Bacterial RNA- D23_1c0326
Neut_0392 (EC 3.5.1.88) metabolizing Zn- dependent hydrolases;
<br>Translation termination factors bacterial
fig|6666666.60966.peg.321 CDS 292108 293136 1 + 1029
Uncharacterized protein -none- D23_1c0327 Neut_0393 with LysM
domain, COG1652 fig|6666666.60966.peg.322 CDS 293235 294356 3 +
1122 Rossmann fold -none- D23_1c0328 Neut_0394 nucleotide-binding
protein Smf possibly involved in DNA uptake
fig|6666666.60966.peg.323 CDS 294438 294896 3 + 459 Protein of
unknown -none- D23_1c0329 Neut_0395 function Smg
fig|6666666.60966.peg.324 CDS 295024 297522 1 + 2499 DNA
topoisomerase III, DNA topoisomerases, D23_1c0330 Neut_0396
Burkholderia type (EC Type I, ATP-independent 5.99.1.2)
fig|6666666.60966.peg.325 CDS 297826 297575 -1 - 252 FIG00858730:
-none- D23_1c0331 Neut_0397 hypothetical protein
fig|6666666.60966.peg.326 CDS 298176 299477 3 + 1302
5-Enolpyruvylshikimate- Chorismate Synthesis; D23_1c0333 Neut_0398
3-phosphate synthase <br>Common Pathway (EC 2.5.1.19) For
Synthesis of Aromatic Compounds (DAHP synthase to chorismate)
fig|6666666.60966.peg.327 CDS 299557 300228 1 + 672 Cytidylate
kinase (EC -none- D23_1c0335 Neut_0399 2.7.4.14)
fig|6666666.60966.peg.328 CDS 300339 302051 3 + 1713 SSU ribosomal
protein -none- D23_1c0336 Neut_0400 S1p fig|6666666.60966.peg.329
CDS 302061 302378 3 + 318 Integration host factor DNA structural
proteins, D23_1c0337 Neut_0401 beta subunit bacterial
fig|6666666.60966.peg.330 CDS 302493 302368 -3 - 126 hypothetical
protein -none- D23_1c0338 NA fig|6666666.60966.peg.33 1 CDS 302902
303597 1 + 696 Orotidine 5'- De Novo Pyrimidine D23_1c0339
Neut_0402 phosphate Synthesis; <br>Riboflavin decarboxylase
(EC synthesis cluster 4.1.1.23) fig|6666666.60966.peg.332 CDS
304632 303592 -3 - 1041 Squalene synthase (EC Hopanes D23_1c0340
Neut_0403 2.5.1.21) fig|6666666.60966.peg.333 CDS 305907 304654 -3
- 1254 Diaminopimelate Lysine Biosynthesis DAP D23_1c0341 Neut_0404
decarboxylase (EC Pathway, GJO scratch 4.1.1.20)
fig|6666666.60966.peg.334 CDS 306026 305904 -2 - 123 hypothetical
protein -none- D23_1c0342 NA fig|6666666.60966.peg.335 CDS 306654
306052 -3 - 603 Probable lipoprotein -none- D23_1c0343 Neut_0405
fig|6666666.60966.peg.336 CDS 307556 306651 -2 - 906 ABC-type
transport -none- D23_1c0344 Neut_0406 system involved in resistance
to organic solvents, periplasmic component
fig|6666666.60966.peg.337 CDS 308341 307583 -1 - 759 Inositol-1-
-none- D23_1c0345 Neut_0407 monophosphatase (EC 3.1.3.25)
fig|6666666.60966.peg.339 CDS 308500 309207 1 + 708 tRNA:Cm32/Um32
RNA methylation; D23_1c0346 Neut_0408 methyltransferase
<br>tRNA modification Bacteria fig|6666666.60966.peg.340 CDS
309905 309291 -2 - 615 Glutathione S- Glutathione: Non-redox
D23_1c0347 Neut_0409 transferase family reactions;
<br>Scaffold protein proteins for [4Fe-4S] cluster assembly
(MRP family) fig|6666666.60966.peg.341 CDS 310042 311418 1 + 1377
Adenylosuccinate lyase De Novo Purine D23_1c0348 Neut_0410 (EC
4.3.2.2) Biosynthesis; <br>Purine conversions
fig|6666666.60966.peg.342 CDS 311556 312146 3 + 591 Heat shock
protein GroEL GroES; <br>Heat D23_1c0349 Neut_0411 GrpE shock
dnaK gene cluster extended; <br>Protein chaperones
fig|6666666.60966.peg.343 CDS 312210 314153 3 + 1944 Chaperone
protein GroEL GroES; <br>Heat D23_1c0350 Neut_0412 DnaK shock
dnaK gene cluster extended; <br>Protein chaperones
fig|6666666.60966.peg.344 CDS 314344 315453 1 + 1110 Chaperone
protein DnaJ GroEL GroES; <br>Heat D23_1c0351 Neut_0413 shock
dnaK gene cluster extended; <br>Protein chaperones
fig|6666666.60966.peg.345 CDS 318894 315550 -3 - 3345 Potassium
efflux system Potassium homeostasis D23_1c0352 Neut_0414 KefA
protein/Small- conductance mechanosensitive channel
fig|6666666.60966.peg.346 CDS 319923 319357 -3 - 567
Transcriptional -none- D23_1c0353 Neut_0415
regulator, TetR family fig|6666666.60966.peg.347 CDS 321174 319990
-3 - 1185 InterPro IPR001327 -none- D23_1c0354 Neut_0416 COGs
COG2072 fig|6666666.60966.peg.348 CDS 321778 321236 -1 - 543
hypothetical protein -none- D23_1c0355 Neut_0417
fig|6666666.60966.peg.349 CDS 322196 322363 2 + 168 hypothetical
protein -none- D23_1c0356 NA fig|6666666.60966.peg.350 CDS 325140
322522 -3 - 2619 Membrane alanine Aminopeptidases (EC D23_1c0357
Neut_0418 aminopeptidase N (EC 3.4.11.--) 3.4.11.2)
fig|6666666.60966.peg.351 CDS 325139 325255 2 + 117 hypothetical
protein -none- D23_1c0358 NA fig|6666666.60966.peg.352 CDS 326547
325213 -3 - 1335 Peptide methionine Peptide methionine D23_1c0359
Neut_0419 sulfoxide reductase sulfoxide reductase; MsrA (EC
1.8.4.11)/ <br>Peptide methionine Thiol:disulfide sulfoxide
reductase; oxidoreductase <br>Peptide methionine associated
with MetSO sulfoxide reductase reductase/Peptide Methionine
sulfoxide reductase MsrB (EC 1.8.4.12) fig|6666666.60966.peg.354
CDS 326909 329791 2 + 2883 Diguanylate -none- D23_1c0360 Neut_0422
cyclase/phosphodiesterase domain 2 (EAL) fig|6666666.60966.peg.355
CDS 331130 329874 -2 - 1257 FIG00858721: -none- D23_1c0361
Neut_0423 hypothetical protein fig|6666666.60966.peg.356 CDS 331369
332730 1 + 1362 O-acetylhomoserine Methionine D23_1c0363 Neut_0424
sulfhydrylase (EC Biosynthesis; 2.5.1.49)/O- <br>Methionine
succinylhomoserine Biosynthesis sulfhydrylase (EC 2.5.1.48)
fig|6666666.60966.peg.357 CDS 334115 332718 -2 - 1398 NnrS protein
involved in Denitrification; D23_1c0364 Neut_0425 response to NO
<br>Nitrosative stress; <br>Oxidative stress
fig|6666666.60966.peg.358 CDS 334992 334066 -3 - 927 Serine
acetyltransferase Cysteine Biosynthesis; D23_1c0365 Neut_0426 (EC
2.3.1.30) <br>Methionine Biosynthesis
fig|6666666.60966.peg.360 CDS 335392 336399 1 + 1008 Glucokinase
(EC 2.7.1.2) Glycolysis and D23_1c0367 Neut_0427 Gluconeogenesis
fig|6666666.60966.peg.361 CDS 336414 337073 3 + 660 Probable -none-
D23_1c0368 Neut_0428 transmembrane protein
fig|6666666.60966.peg.362 CDS 337412 337101 -2 - 312 FIG00858769:
-none- D23_1c0369 Neut_0429 hypothetical protein
fig|6666666.60966.peg.363 CDS 338169 337483 -3 - 687 6- Pentose
phosphate D23_1c0370 Neut_0430 phosphogluconolactonase pathway (EC
3.1.1.31), eukaryotic type fig|6666666.60966.peg.364 CDS 338807
338151 -2 - 657 hydrolase, haloacid -none- D23_1c0371 Neut_0431
dehalogenase-like family fig|6666666.60966.peg.365 CDS 339746
338814 -2 - 933 NAD-dependent CBSS-296591.1.peg.2330 D23_1c0372
Neut_0432 epimerase/dehydratase fig|6666666.60966.peg.366 CDS
340674 339739 -3 - 936 D-3-phosphoglycerate Glycine and Serine
D23_1c0373 Neut_0433 dehydrogenase (EC Utilization; 1.1.1.95)
<br>Pyridoxin (Vitamin B6) Biosynthesis; <br>Serine
Biosynthesis fig|6666666.60966.peg.367 CDS 341432 340671 -2 - 762
2,4-dihydroxyhept-2- -none- D23_1c0374 Neut_0434 ene-1,7-dioic acid
aldolase (EC 4.1.2.--) fig|6666666.60966.peg.368 CDS 342202 341444
-1 - 759 3-deoxy-manno- KDO2-Lipid A D23_1c0375 Neut_0435
octulosonate biosynthesis cluster 2 cytidylyltransferase (EC
2.7.7.38) fig|6666666.60966.peg.370 CDS 342384 342509 3 + 126
hypothetical protein -none- D23_1c0376 NA fig|6666666.60966.peg.371
CDS 342506 343585 2 + 1080 Glycosyl transferase, -none- D23_1c0377
Neut_0436 group 2 family protein fig|6666666.60966.peg.372 CDS
343660 344931 1 + 1272 O-antigen ligase -none- D23_1c0378 Neut_0437
fig|6666666.60966.peg.373 CDS 344931 345620 3 + 690
O-methyltransferase -none- D23_1c0379 Neut_0438 family protein [C1]
fig|6666666.60966.peg.374 CDS 345673 345930 1 + 258 FIG00859064:
-none- D23_1c0380 Neut_0439 hypothetical protein
fig|6666666.60966.peg.375 CDS 345980 346498 2 + 519 Mlr4354 like
protein -none- D23_1c0381 Neut_0440 fig|6666666.60966.peg.376 CDS
346511 346858 2 + 348 Arsenate reductase (EC Anaerobic respiratory
D23_1c0382 Neut_0441 1.20.4.1) reductases; <br>Transcription
repair cluster fig|6666666.60966.peg.377 CDS 347305 346916 -1 - 390
LSU ribosomal protein -none- D23_1c0383 Neut_0442 L19p
fig|6666666.60966.peg.378 CDS 348122 347277 -2 - 846 tRNA
(Guanine37-N1)- RNA methylation; D23_1c0384 Neut_0443
methyltransferase (EC <br>Ribosome 2.1.1.31) biogenesis
bacterial; <br>tRNA modification Bacteria
fig|6666666.60966.peg.379 CDS 348636 348130 -3 - 507 16S rRNA
processing Ribosome biogenesis D23_1c0385 Neut_0444 protein RimM
bacterial fig|6666666.60966.peg.381 CDS 349157 350437 2 + 1281
Glycolate Glycolate, glyoxylate D23_1c0386 Neut_0446 dehydrogenase
(EC interconversions; 1.1.99.14), iron-sulfur
<br>Photorespiration subunit GlcF (oxidative C2 cycle)
fig|6666666.60966.peg.382 CDS 350492 351118 2 + 627 Uncharacterized
Ubiquinone Biosynthesis- D23_1c0387 Neut_0447 hydroxylase PA0655
gjo fig|6666666.60966.peg.383 CDS 351152 351712 2 + 561 UPF0301
protein YqgE -none- D23_1c0388 Neut_0448 fig|6666666.60966.peg.384
CDS 351705 352178 3 + 474 Putative Holliday -none- D23_1c0389
Neut_0449 junction resolvase (EC 3.1.--.--)
fig|6666666.60966.peg.385 CDS 352165 352668 1 + 504 Uracil De Novo
Pyrimidine D23_1c0390 Neut_0450 phosphoribosyltransferase
Synthesis; <br>De Novo (EC 2.4.2.9)/ Pyrimidine Synthesis;
Pyrimidine operon <br>pyrimidine regulatory protein PyrR
conversions fig|6666666.60966.peg.386 CDS 352856 353806 2 + 951
Aspartate De Novo Pyrimidine D23_1c0391 Neut_0451
carbamoyltransferase Synthesis (EC 2.1.3.2)
fig|6666666.60966.peg.387 CDS 353822 355093 2 + 1272 Dihydroorotase
(EC De Novo Pyrimidine D23_1c0392 Neut_0452 3.5.2.3) Synthesis;
<br>Zinc regulated enzymes fig|6666666.60966.peg.388 CDS
355217 357322 2 + 2106 Oligopeptidase A (EC Protein degradation
D23_1c0393 Neut_0453 3.4.24.70) fig|6666666.60966.peg.389 CDS
357558 358709 3 + 1152 Carbamoyl-phosphate De Novo Pyrimidine
D23_1c0394 Neut_0454 synthase small chain Synthesis; (EC 6.3.5.5)
<br>Macromolecular synthesis operon fig|6666666.60966.peg.390
CDS 358735 361932 1 + 3198 Carbamoyl-phosphate De Novo Pyrimidine
D23_1c0395 Neut_0455 synthase large chain (EC Synthesis; 6.3.5.5)
<br>Macromolecular synthesis operon fig|6666666.60966.peg.391
CDS 362117 362593 2 + 477 Transcription Transcription factors
D23_1c0396 Neut_0456 elongation factor GreA bacterial
fig|6666666.60966.peg.392 CDS 363579 362608 -3 - 972
ErfK/YbiS/YcfS/YnhG -none- D23_1c0397 Neut_0457 family protein
fig|6666666.60966.peg.393 CDS 364226 366052 2 + 1827
Long-chain-fatty-acid-- Biotin biosynthesis; D23_1c0398 Neut_0458
CoA ligase (EC 6.2.1.3) <br>Biotin synthesis cluster;
<br>Fatty acid metabolism cluster fig|6666666.60966.peg.394
CDS 366141 367064 3 + 924 FIG010773: NAD- -none- D23_1c0399
Neut_0459 dependent epimerase/dehydratase fig|6666666.60966.peg.395
CDS 367176 367430 3 + 255 phosphopantetheine- -none- D23_1c0400
Neut_0460 binding fig|6666666.60966.peg.396 CDS 367430 368617 2 +
1188 Aminotransferase class -none- D23_1c0401 Neut_0461 II, serine
palmitoyltransferase like (EC 2.3.1.50) fig|6666666.60966.peg.397
CDS 368669 369427 2 + 759 COG1496: -none- D23_1c0402 Neut_0462
Uncharacterized conserved protein fig|6666666.60966.peg.398 CDS
369615 370427 3 + 813 Zinc transporter, ZIP -none- D23_1c0403
Neut_0463 family fig|6666666.60966.peg.399 CDS 373049 370434 -2 -
2616 Dolichyl-phosphate -none- D23_1c0404 Neut_0464 beta-D-
mannosyltransferase (EC: 2.4.1.83) fig|6666666.60966.peg.400 CDS
374173 373157 -1 - 1017 FIG004453: protein CBSS- D23_1c0405
Neut_0465 YceG like 323097.3.peg.2594; <br>Cluster containing
Alanyl-tRNA synthetase; <br>tRNA modification Bacteria
fig|6666666.60966.peg.401 CDS 374277 374140 -3 - 138 hypothetical
protein -none- D23_1c0406 NA fig|6666666.60966.peg.402 CDS 375542
374301 -2 - 1242 3-oxoacyl-[acyl-carrier- Fatty Acid Biosynthesis
D23_1c0407 Neut_0466 protein] synthase, KASII FASII (EC 2.3.1.41)
fig|6666666.60966.peg.403 CDS 375822 375577 -3 - 246 Acyl carrier
protein Fatty Acid Biosynthesis D23_1c0408 Neut_0467 FASII;
<br>Glycerolipid and Glycerophospholipid Metabolism in
Bacteria fig|6666666.60966.peg.405 CDS 376731 375988 -3 - 744
3-oxoacyl-[acyl-carrier Fatty Acid Biosynthesis D23_1c0409
Neut_0468 protein] reductase (EC FASII 1.1.1.100)
fig|6666666.60966.peg.406 CDS 377726 376788 -2 - 939 Malonyl
CoA-acyl Fatty Acid Biosynthesis D23_1c0410 Neut_0469 carrier
protein FASII transacylase (EC 2.3.1.39) fig|6666666.60966.peg.407
CDS 378692 377730 -2 - 963 3-oxoacyl-[acyl-carrier- Fatty Acid
Biosynthesis D23_1c0411 Neut_0470 protein] synthase, FASII KASIII
(EC 2.3.1.41) fig|6666666.60966.peg.408 CDS 379722 378703 -3 - 1020
Phosphate:acyl-ACP Glycerolipid and D23_1c0412 Neut_0471
acyltransferase PlsX Glycerophospholipid Metabolism in Bacteria
fig|6666666.60966.peg.409 CDS 379982 379800 -2 - 183 LSU ribosomal
protein -none- D23_1c0414 Neut_0472 L32p fig|6666666.60966.peg.410
CDS 380510 380007 -2 - 504 COG1399 protein, -none- D23_1c0415
Neut_0473 clustered with ribosomal protein L32p
fig|6666666.60966.peg.411 CDS 380534 381175 2 + 642 FIG146278:
-none- D23_1c0416 Neut_0474 Maf/YceF/YhdE family protein
fig|6666666.60966.peg.412 CDS 381292 381684 1 + 393 FIG00858587:
-none- D23_1c0417 Neut_0475 hypothetical protein
fig|6666666.60966.peg.413 CDS 381793 383217 1 + 1425 Heavy metal
RND efflux Cobalt-zinc-cadmium D23_1c0418 Neut_0476 outer membrane
resistance protein, CzcC family fig|6666666.60966.peg.414 CDS
383214 384710 3 + 1497 Cobalt/zinc/cadmium Cobalt-zinc-cadmium
D23_1c0419 Neut_0477 efflux RND transporter, resistance membrane
fusion protein, CzcB family fig|6666666.60966.peg.415 CDS 384811
388020 1 + 3210 Cobalt-zinc-cadmium Cobalt-zinc-cadmium D23_1c0421
Neut_0478
resistance protein CzcA; resistance; <br>Cobalt- Cation
efflux system zinc-cadmium resistance protein CusA
fig|6666666.60966.peg.416 CDS 388294 388731 1 + 438 FIG00858457:
-none- D23_1c0423 Neut_0479 hypothetical protein
fig|6666666.60966.peg.417 CDS 388756 389043 1 + 288 FIG00858508:
-none- D23_1c0424 Neut_0480 hypothetical protein
fig|6666666.60966.peg.418 CDS 389040 389948 3 + 909 FIG00858931:
-none- D23_1c0425 Neut_0481 hypothetical protein
fig|6666666.60966.peg.419 CDS 389941 391068 1 + 1128 hypothetical
protein -none- D23_1c0426 Neut_0482 fig|6666666.60966.peg.420 CDS
392521 391079 -1 - 1443 Mg/Co/Ni transporter Magnesium transport
D23_1c0427 Neut_0483 MgtE/CBS domain fig|6666666.60966.peg.424 CDS
394723 393761 -1 - 963 Mobile element protein -none- D23_1c0430
Neut_1746 fig|6666666.60966.peg.425 CDS 394947 394834 -3 - 114
hypothetical protein -none- D23_1c0431 NA fig|6666666.60966.peg.426
CDS 394946 395251 2 + 306 hypothetical protein -none- D23_1c0432
Neut_0486 fig|6666666.60966.peg.427 CDS 395968 395309 -1 - 660
COG1272: Predicted -none- D23_1c0433 Neut_0487 membrane protein
hemolysin III homolog fig|6666666.60966.peg.428 CDS 396481 396179
-1 - 303 hypothetical protein -none- D23_1c0434 Neut_0488
fig|6666666.60966.peg.430 CDS 397189 396863 -1 - 327 hypothetical
protein -none- D23_1c0435 Neut_0490 fig|6666666.60966.peg.433 CDS
397653 398393 3 + 741 cAMP-binding proteins- cAMP signaling in
D23_1c0436 Neut_0491 catabolite gene bacteria activator and
regulatory subunit of cAMP- dependent protein kinases
fig|6666666.60966.peg.434 CDS 398690 398424 -2 - 267 Putative
lipoprotein -none- D23_1c0437 Neut_0492 fig|6666666.60966.peg.435
CDS 399146 398973 -2 - 174 hypothetical protein -none- D23_1c0438
NA fig|6666666.60966.peg.436 CDS 399498 399373 -3 - 126
hypothetical protein -none- D23_1c0439 NA fig|6666666.60966.peg.437
CDS 400841 399609 -2 - 1233 hypothetical protein -none- D23_1c0440
Neut_0494 fig|6666666.60966.peg.438 CDS 401592 400858 -3 - 735
Monofunctional Peptidoglycan D23_1c0441 Neut_0495 biosynthetic
Biosynthesis peptidoglycan transglycosylase (EC 2.4.2.--)
fig|6666666.60966.peg.439 CDS 402422 401589 -2 - 834 Shikimate 5-
Chorismate Synthesis; D23_1c0442 Neut_0496 dehydrogenase I alpha
<br>Cluster containing (EC 1.1.1.25) Alanyl-tRNA synthetase;
<br>Common Pathway For Synthesis of Aromatic Compounds (DAHP
synthase to chorismate) fig|6666666.60966.peg.440 CDS 403340 402456
-2 - 885 TonB protein -none- D23_1c0443 Neut_0497
fig|6666666.60966.peg.441 CDS 405237 403378 -3 - 1860
Exoribonuclease II (EC RNA processing and D23_1c0444 Neut_0498
3.1.13.1) degradation, bacterial fig|6666666.60966.peg.443 CDS
405594 406985 3 + 1392 Glutamyl-tRNA Heme and Siroheme D23_1c0445
Neut_0499 synthetase (EC 6.1.1.17) Biosynthesis; <br>tRNA
aminoacylation, Glu and Gln fig|6666666.60966.peg.444 CDS 407045
410752 2 + 3708 5- Methionine Biosynthesis D23_1c0446 Neut_0500
methyltetrahydrofolate-- homocysteine methyltransferase (EC
2.1.1.13) fig|6666666.60966.peg.445 CDS 410924 412267 2 + 1344
NADP-specific Arginine and Ornithine D23_1c0447 Neut_0501 glutamate
Degradation; dehydrogenase (EC <br>Glutamate 1.4.1.4)
dehydrogenases; <br>Glutamine, Glutamate, Aspartate and
Asparagine Biosynthesis; <br>Proline Synthesis
fig|6666666.60966.peg.446 CDS 412461 414368 3 + 1908 Soluble lytic
murein Murein Hydrolases D23_1c0449 Neut_0502 transglycosylase
precursor (EC 3.2.1.--) fig|6666666.60966.peg.447 CDS 414379 415617
1 + 1239 tRNA A cluster relating to D23_1c0450 Neut_0503
nucleotidyltransferase Tryptophanyl-tRNA (EC 2.7.7.21) (EC
synthetase; 2.7.7.25) <br>Polyadenylation bacterial;
<br>tRNA nucleotidyltransferase fig|6666666.60966.peg.448 CDS
417316 415592 -1 - 1725 Phospholipid- N-linked Glycosylation in
D23_1c0451 Neut_0504 lipopolysaccharide ABC Bacteria transporter
fig|6666666.60966.peg.449 CDS 418171 417335 -1 - 837
Diaminopimelate CBSS-84588.1.peg.1247; D23_1c0452 Neut_0505
epimerase (EC 5.1.1.7) <br>Lysine Biosynthesis DAP Pathway,
GJO scratch fig|6666666.60966.peg.450 CDS 418345 418193 -1 - 153
hypothetical protein -none- D23_1c0453 NA fig|6666666.60966.peg.451
CDS 418574 419011 2 + 438 Predicted secretion Predicted secretion
D23_1c0454 Neut_0506 system X protein GspG- system X like 3
fig|6666666.60966.peg.452 CDS 419030 420214 2 + 1185 Predicted
secretion Predicted secretion D23_1c0455 Neut_0507 system X protein
GspF- system X like fig|6666666.60966.peg.453 CDS 420211 421905 1 +
1695 Predicted secretion Predicted secretion D23_1c0456 Neut_0508
system X protein GspE- system X like fig|6666666.60966.peg.454 CDS
421910 422731 2 + 822 Predicted secretion Predicted secretion
D23_1c0457 Neut_0509 system X FIG084745: system X hypothetical
protein fig|6666666.60966.peg.455 CDS 422772 423260 3 + 489
Predicted secretion Predicted secretion D23_1c0458 Neut_0510 system
X system X transmembrane protein 1 fig|6666666.60966.peg.472 CDS
440367 440753 3 + 387 Mobile element protein -none- D23_1c0476
Neut_0884 fig|6666666.60966.peg.473 CDS 440716 441171 1 + 456
Mobile element protein -none- D23_1c0477 Neut_2502
fig|6666666.60966.peg.474 CDS 441829 441158 -1 - 672 Gluconate 2-
D-gluconate and D23_1c0478 NA dehydrogenase (EC ketogluconates
1.1.99.3), membrane- metabolism bound, gamma subunit
fig|6666666.60966.peg.475 CDS 444093 441973 -3 - 2121 diguanylate
-none- D23_1c0479 Neut_0525 cyclase/phosphodiesterase (GGDEF &
EAL domains) with PAS/PAC sensor(s) fig|6666666.60966.peg.476 CDS
444457 444311 -1 - 147 hypothetical protein -none- D23_1c0480 NA
fig|6666666.60966.peg.478 CDS 444629 445810 2 + 1182
NAD(FAD)-utilizing -none- D23_1c0481 Neut_0526 dehydrogenases
fig|6666666.60966.peg.479 CDS 446569 445952 -1 -- 618 Methionine
-none- D23_1c0482 Neut_0527 biosynthesis protein MetW
fig|6666666.60966.peg.480 CDS 447733 446600 -1 - 1134 Homoserine O-
Methionine Biosynthesis D23_1c0483 Neut_0528 acetyltransferase (EC
2.3.1.31) fig|6666666.60966.peg.481 CDS 449559 447832 -3 - 1728
Phosphoenolpyruvate- -none- D23_1c0484 Neut_0529 protein
phosphotransferase of PTS system (EC 2.7.3.9)
fig|6666666.60966.peg.482 CDS 449825 449556 -2 - 270 Phosphocarrier
protein, -none- D23_1c0485 Neut_0530 nitrogen regulation associated
fig|6666666.60966.peg.483 CDS 450219 449815 -3 - 405 Sugar
transport PTS -none- D23_1c0486 Neut_0531 system IIa component
fig|6666666.60966.peg.484 CDS 450568 451605 1 + 1038
Phosphatidylglycerophosphatase Glycerolipid and D23_1c0488
Neut_0532 B (EC 3.1.3.27) Glycerophospholipid Metabolism in
Bacteria fig|6666666.60966.peg.485 CDS 451971 451705 -3 - 267 HrgA
protein -none- D23_1c0489 Neut_2454 fig|6666666.60966.peg.486 CDS
452384 453631 2 + 1248 Mobile element protein -none- D23_1c0490
Neut_0357 fig|6666666.60966.peg.487 CDS 455203 454049 -1 - 1155
hypothetical protein -none- D23_1c0491 NA fig|6666666.60966.peg.488
CDS 455538 455371 -3 - 168 hypothetical protein -none- D23_1c0492
NA fig|6666666.60966.peg.489 CDS 455581 456603 1 + 1023 Lipolytic
enzyme, G-D-S-L -none- D23_1c0493 Neut_0534
fig|6666666.60966.peg.490 CDS 457214 456669 -2 - 546
N-acetylmuramoyl-L- Recycling of D23_1c0494 Neut_0535 alanine
amidase (EC Peptidoglycan Amino 3.5.1.28) AmpD Acids
fig|6666666.60966.peg.491 CDS 457304 457951 2 + 648 Thymidylate
kinase (EC pyrimidine conversions D23_1c0495 Neut_0536 2.7.4.9)
fig|6666666.60966.peg.492 CDS 461332 458087 -1 - 3246 Type I
restriction- Restriction-Modification D23_1c0496 Neut_0537
modification system, System; <br>Type I restriction subunit R
(EC Restriction-Modification 3.1.21.3) fig|6666666.60966.peg.493
CDS 462292 461345 -1 - 948 Putative DNA-binding
Restriction-Modification D23_1c0497 NA protein in cluster with
System Type I restriction- modification system
fig|6666666.60966.peg.494 CDS 462416 462285 -2 - 132 hypothetical
protein -none- D23_1c0498 NA fig|6666666.60966.peg.495 CDS 463405
462413 -1 - 993 hypothetical protein -none- D23_1c0499 NA
fig|6666666.60966.peg.496 CDS 464694 463405 -3 - 1290 Type I
restriction- Restriction-Modification D23_1c0500 Neut_0540
modification system, System; <br>Type I specificity subunit S
(EC Restriction-Modification 3.1.21.3) fig|6666666.60966.peg.497
CDS 466246 464684 -1 - 1563 Type I restriction-
Restriction-Modification D23_1c0501 Neut_0541 modification system,
System; <br>Type I DNA-methyltransferase
Restriction-Modification subunit M (EC 2.1.1.72)
fig|6666666.60966.peg.498 CDS 467880 466453 -3 - 1428 Na+/H+
antiporter -none- D23_1c0502 Neut_0542 NhaC
fig|6666666.60966.peg.499 CDS 468057 467896 -3 - 162 hypothetical
protein -none- D23_1c0503 NA fig|6666666.60966.peg.500 CDS 468126
469190 3 + 1065 DNA polymerase III -none- D23_1c0504 Neut_0543
delta prime subunit (EC 2.7.7.7) fig|6666666.60966.peg.501 CDS
469691 469194 -2 - 498 hypothetical protein -none- D23_1c0505
Neut_0544 fig|6666666.60966.peg.502 CDS 469703 469870 2 + 168
hypothetical protein -none- D23_1c0506 NA fig|6666666.60966.peg.503
CDS 470025 471155 3 + 1131 Magnesium and cobalt Magnesium transport
D23_1c0508 Neut_0545 transport protein CorA
fig|6666666.60966.peg.504 CDS 471202 471447 1 + 246 Mobile element
protein -none- D23_1c0509 Neut_0884 fig|6666666.60966.peg.505 CDS
471504 471617 3 + 114 hypothetical protein -none- D23_1c0510
Neut_0547 fig|6666666.60966.peg.506 CDS 471862 473013 1 + 1152
conserved hypothetical -none- D23_1c0511 Neut_0548 protein
fig|6666666.60966.peg.507 CDS 473412 473957 3 + 546 Uncharacterized
protein -none- D23_1c0512 Neut_0550 conserved in bacteria
fig|6666666.60966.peg.508 CDS 474111 474269 3 + 159 Mobile element
protein -none- D23_1c0513 NA fig|6666666.60966.peg.510 CDS 474450
474653 3 + 204 hypothetical protein -none- D23_1c0514 NA
fig|6666666.60966.peg.512 CDS 475553 476005 2 + 453 SSU ribosomal
protein Mycobacterium D23_1c0515 Neut_0554 S7p (S5e) virulence
operon involved in protein synthesis (SSU ribosomal proteins)
fig|6666666.60966.peg.513 CDS 476121 478166 3 + 2046
Translation
elongation Mycobacterium D23_1c0516 Neut_0555 factor G virulence
operon involved in protein synthesis (SSU ribosomal proteins);
<br>Translation elongation factor G family;
<br>Translation elongation factors bacterial;
<br>Universal GTPases fig|6666666.60966.peg.514 CDS 478196
479386 2 + 1191 Translation elongation Mycobacterium D23_1c0517
Neut_0556 factor Tu virulence operon involved in protein synthesis
(SSU ribosomal proteins); <br>Translation elongation factors
bacterial; <br>Universal GTPases fig|6666666.60966.peg.515
CDS 479569 479775 1 + 207 SSU ribosomal protein -none- D23_1c0518
Neut_0557 S10p (S20e) fig|6666666.60966.peg.516 CDS 479823 480476 3
+ 654 LSU ribosomal protein -none- D23_1c0519 Neut_0558 L3p (L3e)
fig|6666666.60966.peg.517 CDS 480494 481114 2 + 621 LSU ribosomal
protein -none- D23_1c0520 Neut_0559 L4p (L1e)
fig|6666666.60966.peg.518 CDS 481111 481446 1 + 336 LSU ribosomal
protein -none- D23_1c0521 Neut_0560 L23p (L23Ae)
fig|6666666.60966.peg.519 CDS 481446 482279 3 + 834 LSU ribosomal
protein -none- D23_1c0522 Neut_0561 L2p (L8e)
fig|6666666.60966.peg.520 CDS 482948 483595 2 + 648 SSU ribosomal
protein -none- D23_1c0523 Neut_0564 S3p (S3e)
fig|6666666.60966.peg.521 CDS 483680 484096 2 + 417 LSU ribosomal
protein -none- D23_1c0524 Neut_0565 L16p (L10e)
fig|6666666.60966.peg.524 CDS 485008 485331 1 + 324 LSU ribosomal
protein -none- D23_1c0525 Neut_0569 L24p (L26e)
fig|6666666.60966.peg.525 CDS 485458 485886 1 + 429 LSU ribosomal
protein -none- D23_1c0526 Neut_0570 L5p (L11e)
fig|6666666.60966.peg.526 CDS 486881 487222 2 + 342 LSU ribosomal
protein -none- D23_1c0527 Neut_0573 L6p (L9e)
fig|6666666.60966.peg.527 CDS 487678 488151 1 + 474 SSU ribosomal
protein -none- D23_1c0528 Neut_0575 S5p (S2e)
fig|6666666.60966.peg.528 CDS 488796 490118 3 + 1323 Preprotein
translocase -none- D23_1c0530 Neut_0578 secY subunit (TC 3.A.5.1.1)
fig|6666666.60966.peg.530 CDS 491337 491963 3 + 627 SSU ribosomal
protein -none- D23_1c0531 Neut_0582 S4p (S9e)
fig|6666666.60966.peg.531 CDS 492065 492997 2 + 933 DNA-directed
RNA RNA polymerase D23_1c0532 Neut_0583 polymerase alpha bacterial
subunit (EC 2.7.7.6) fig|6666666.60966.peg.532 CDS 494213 493998 -2
- 216 Putative oligoketide Possible RNA D23_1c0534 Neut_0586
cyclase/dehydratase or degradation cluster lipid transport protein
YfjG fig|6666666.60966.peg.533 CDS 494546 494995 2 + 450
tmRNA-binding protein Heat shock dnaK gene D23_1c0535 Neut_0587
SmpB cluster extended; <br>Translation termination factors
bacterial fig|6666666.60966.peg.534 CDS 495005 496075 2 + 1071 Heme
A synthase, Biogenesis of D23_1c0536 Neut_0588 cytochrome oxidase
cytochrome c oxidases biogenesis protein Cox15-CtaA
fig|6666666.60966.peg.535 CDS 496163 496582 2 + 420 Probable -none-
D23_1c0537 Neut_0589 transmembrane protein
fig|6666666.60966.peg.537 CDS 496945 498528 1 + 1584 DNA polymerase
III DNA processing cluster D23_1c0538 Neut_0590 subunits gamma and
tau (EC 2.7.7.7) fig|6666666.60966.peg.538 CDS 498545 498868 2 +
324 FIG000557: DNA processing cluster D23_1c0539 Neut_0591
hypothetical protein co- occurring with RecR
fig|6666666.60966.peg.539 CDS 498922 499740 1 + 819 Pseudouridine
synthase -none- D23_1c0540 Neut_0592 family protein
fig|6666666.60966.peg.540 CDS 500690 499770 -2 - 921
Protein-N(5)-glutamine -none- D23_1c0541 Neut_0593
methyltransferase PrmB, methylates LSU ribosomal protein L3p
fig|6666666.60966.peg.541 CDS 500738 501241 2 + 504 tRNA-specific
tRNA modification D23_1c0542 Neut_0594 adenosine-34 Bacteria;
<br>tRNA deaminase (EC 3.5.4.--) processing
fig|6666666.60966.peg.542 CDS 501238 501717 1 + 480 Conserved
domain -none- D23_1c0543 Neut_0595 protein
fig|6666666.60966.peg.543 CDS 501779 503389 2 + 1611 NAD-dependent
malic Pyruvate metabolism I: D23_1c0544 Neut_0596 enzyme (EC
1.1.1.38) anaplerotic reactions, PEP fig|6666666.60966.peg.544 CDS
504268 503438 -1 - 831 Phosphoserine Glycine and Serine D23_1c0545
Neut_0597 phosphatase (EC Utilization; <br>Serine 3.1.3.3)
Biosynthesis; <br>Serine Biosynthesis
fig|6666666.60966.peg.545 CDS 505831 504356 -1 - 1476 FIG00858790:
-none- D23_1c0546 Neut_0598 hypothetical protein
fig|6666666.60966.peg.547 CDS 506088 507581 3 + 1494 Cytosol
aminopeptidase Aminopeptidases (EC D23_1c0547 Neut_0599 PepA (EC
3.4.11.1) 3.4.11.--); <br>Dehydrogenase complexes
fig|6666666.60966.peg.548 CDS 507615 508043 3 + 429 DNA polymerase
III chi -none- D23_1c0548 Neut_0600 subunit (EC 2.7.7.7)
fig|6666666.60966.peg.549 CDS 508116 508517 3 + 402 FIG00859089:
-none- D23_1c0549 Neut_0601 hypothetical protein
fig|6666666.60966.peg.550 CDS 508581 511334 3 + 2754 Valyl-tRNA
synthetase tRNA aminoacylation, D23_1c0550 Neut_0602 (EC 6.1.1.9)
Val fig|6666666.60966.peg.551 CDS 511430 512500 2 + 1071
Uroporphyrinogen III Heme and Siroheme D23_1c0551 Neut_0603
decarboxylase (EC Biosynthesis 4.1.1.37) fig|6666666.60966.peg.552
CDS 513466 512660 -1 - 807 Maebl -none- D23_1c0552 Neut_0604
fig|6666666.60966.peg.553 CDS 514503 513616 -3 - 888 Succinyl-CoA
ligase TCA Cycle D23_1c0553 Neut_0605 [ADP-forming] alpha chain (EC
6.2.1.5) fig|6666666.60966.peg.554 CDS 515705 514533 -2 - 1173
Succinyl-CoA ligase TCA Cycle D23_1c0554 Neut_0606 [ADP-forming]
beta chain (EC 6.2.1.5) fig|6666666.60966.peg.555 CDS 516828 515878
-3 - 951 Malyl-CoA lyase (EC Photorespiration D23_1c0555 Neut_0607
4.1.3.24) (oxidative C2 cycle) fig|6666666.60966.peg.557 CDS 518554
517079 -1 - 1476 Glycogen synthase, Glycogen metabolism D23_1c0557
Neut_0608 ADP-glucose transglucosylase (EC 2.4.1.21)
fig|6666666.60966.peg.558 CDS 520242 518608 -3 - 1635
Glucose-6-phosphate Glycolysis and D23_1c0558 Neut_0609 isomerase
(EC 5.3.1.9) Gluconeogenesis fig|6666666.60966.peg.559 CDS 521449
520271 -1 - 1179 3-ketoacyl-CoA thiolase Acetyl-CoA fermentation
D23_1c0559 Neut_0610 (EC 2.3.1.16) @ Acetyl- to Butyrate;
<br>Biotin CoA acetyltransferase biosynthesis;
<br>Biotin (EC 2.3.1.9) synthesis cluster; <br>Butanol
Biosynthesis; <br>Butyrate metabolism cluster;
<br>Fatty acid metabolism cluster; <br>Isoprenoid
Biosynthesis; <br>Polyhydroxybutyrate metabolism;
<br>Polyhydroxybutyrate metabolism fig|6666666.60966.peg.560
CDS 522790 521459 -1 - 1332 ATP-dependent hsl Proteasome bacterial;
D23_1c0560 Neut_0611 protease ATP-binding <br>Proteolysis in
subunit HslU bacteria, ATP-dependent fig|6666666.60966.peg.561 CDS
523346 522825 -2 - 522 ATP-dependent Proteasome bacterial;
D23_1c0561 Neut_0612 protease HslV (EC <br>Proteolysis in
3.4.25.--) bacteria, ATP-dependent fig|6666666.60966.peg.563 CDS
523758 523555 -3 - 204 DNA-directed RNA RNA polymerase D23_1c0562
Neut_0613 polymerase omega bacterial subunit (EC 2.7.7.6)
fig|6666666.60966.peg.564 CDS 524414 523809 -2 - 606 Guanylate
kinase (EC CBSS- D23_1c0563 Neut_0614 2.7.4.8) 323097.3.peg.2594;
<br>Purine conversions fig|6666666.60966.peg.565 CDS 525166
524684 -1 - 483 Dihydroneopterin Folate Biosynthesis D23_1c0565
Neut_0615 triphosphate pyrophosphohydrolase type 2 (nudB)
fig|6666666.60966.peg.566 CDS 526961 525180 -2 - 1782 Aspartyl-tRNA
tRNA aminoacylation, D23_1c0566 Neut_0616 synthetase (EC 6.1.1.12)
Asp and Asn; <br>tRNA @ Aspartyl-tRNA(Asn) aminoacylation,
Asp and synthetase (EC 6.1.1.23) Asn fig|6666666.60966.peg.567 CDS
527054 527206 2 + 153 hypothetical protein -none- D23_1c0567 NA
fig|6666666.60966.peg.568 CDS 528907 527456 -1 - 1452
Mannose-1-phosphate Mannose Metabolism; D23_1c0569 Neut_0618
guanylyltransferase <br>Mannose (GDP) (EC 2.7.7.22)/
Metabolism Mannose-6-phosphate isomerase (EC 5.3.1.8)
fig|6666666.60966.peg.569 CDS 530083 528971 -1 - 1113 UDP-N- CMP-N-
D23_1c0570 Neut_0619 acetylglucosamine 2- acetylneuraminate
epimerase (EC 5.1.3.14) Biosynthesis; <br>Sialic Acid
Metabolism fig|6666666.60966.peg.570 CDS 530171 530284 2 + 114
hypothetical protein -none- D23_1c0571 NA fig|6666666.60966.peg.571
CDS 530407 530535 1 + 129 hypothetical protein -none- D23_1c0572 NA
fig|6666666.60966.peg.572 CDS 530637 531041 3 + 405 Truncated
hemoglobins -none- D23_1c0573 Neut_0620 fig|6666666.60966.peg.573
CDS 531034 532257 1 + 1224 NnrS protein involved in
Denitrification; D23_1c0574 Neut_0621 response to NO
<br>Nitrosative stress; <br>Oxidative stress
fig|6666666.60966.peg.574 CDS 532298 532738 2 + 441 putative
membrane -none- D23_1c0575 Neut_0622 protein
fig|6666666.60966.peg.575 CDS 532841 533326 2 + 486 FIG001943:
Broadly distributed D23_1c0576 Neut_0623 hypothetical protein
proteins not in YajQ subsystems fig|6666666.60966.peg.576 CDS
534972 533485 -3 - 1488 FIG00859034: -none- D23_1c0577 Neut_0624
hypothetical protein fig|6666666.60966.peg.577 CDS 535028 535240 2
+ 213 hypothetical protein -none- D23_1c0578 NA
fig|6666666.60966.peg.578 CDS 536092 535289 -1 - 804 FIG00858513:
-none- D23_1c0579 Neut_0626 hypothetical protein
fig|6666666.60966.peg.579 CDS 537497 536616 -2 - 882 hypothetical
protein -none- D23_1c0581 NA fig|6666666.60966.peg.580 CDS 538547
537726 -2 - 822 hypothetical protein -none- D23_1c0582 NA
fig|6666666.60966.peg.581 CDS 539856 538789 -3 - 1068 Conserved
domain -none- D23_1c0583 NA protein fig|6666666.60966.peg.582 CDS
540712 539849 -1 - 864 Conserved domain -none- D23_1c0584 NA
protein fig|6666666.60966.peg.583 CDS 541704 540841 -3 - 864
possible long-chain N- -none- D23_1c0585 Neut_0638
acyl amino acid synthase fig|6666666.60966.peg.584 CDS 541934
541812 -2 - 123 hypothetical protein -none- D23_1c0586 NA
fig|6666666.60966.peg.586 CDS 542270 542467 2 + 198 conserved
hypothetical -none- D23_1c0587 Neut_0639 protein
fig|6666666.60966.peg.587 CDS 542451 542618 3 + 168 hypothetical
protein -none- D23_1c0588 Neut_0640 fig|6666666.60966.peg.588 CDS
542602 542724 1 + 123 hypothetical protein -none- D23_1c0589
Neut_0641 fig|6666666.60966.peg.590 CDS 543111 544673 3 + 1563
Putative inner -none- D23_1c0590 Neut_0642 membrane protein
fig|6666666.60966.peg.591 CDS 544721 544834 2 + 114 hypothetical
protein -none- D23_1c0591 NA fig|6666666.60966.peg.592 CDS 545193
546098 3 + 906 Membrane-bound lytic CBSS-228410.1.peg.134;
D23_1c0592 Neut_0643 murein transglycosylase <br>CBSS- D
precursor (EC 3.2.1.--) 342610.3.peg.1536; <br>Murein
Hydrolases fig|6666666.60966.peg.593 CDS 546933 546274 -3 - 660
Endonuclease III (EC DNA Repair Base D23_1c0593 Neut_0644
4.2.99.18) Excision fig|6666666.60966.peg.594 CDS 547586 546930 -2
- 657 Electron transport -none- D23_1c0594 Neut_0645 complex
protein RnfB fig|6666666.60966.peg.595 CDS 548604 547576 -3 - 1029
Dihydroorotate De Novo Pyrimidine D23_1c0595 Neut_0646
dehydrogenase (EC Synthesis 1.3.3.1) fig|6666666.60966.peg.596 CDS
549246 548605 -3 - 642 Arginine-tRNA-protein Protein degradation
D23_1c0596 Neut_0647 transferase (EC 2.3.2.8)
fig|6666666.60966.peg.597 CDS 550041 549343 -3 - 699
Leucyl/phenylalanyl- Protein degradation D23_1c0597 Neut_0648
tRNA-protein transferase (EC 2.3.2.6) fig|6666666.60966.peg.598 CDS
550783 550328 -1 - 456 Mobile element protein -none- D23_1c0598
Neut_2502 fig|6666666.60966.peg.599 CDS 551132 550746 -2 - 387
Mobile element protein -none- D23_1c0599 Neut_0884
fig|6666666.60966.peg.600 CDS 551404 551517 1 + 114 hypothetical
protein -none- D23_1c0600 NA fig|6666666.60966.peg.601 CDS 551625
552500 3 + 876 FIG00859053: -none- D23_1c0601 Neut_0650
hypothetical protein fig|6666666.60966.peg.602 CDS 554066 552684 -2
- 1383 UDP-N- Peptidoglycan D23_1c0602 Neut_0651 acetylmuramate:L-
biosynthesis--gjo; alanyl-gamma-D- <br>Recycling of
glutamyl-meso- Peptidoglycan Amino diaminopimelate ligase Acids (EC
6.3.2.--) fig|6666666.60966.peg.603 CDS 554191 555363 1 + 1173 NADH
dehydrogenase Respiratory D23_1c0603 Neut_0652 (EC 1.6.99.3)
dehydrogenases 1; <br>Riboflavin synthesis cluster
fig|6666666.60966.peg.604 CDS 556325 555387 -2 - 939 Mutator mutT
protein Nudix proteins D23_1c0604 Neut_0653 (7,8-dihydro-8-
(nucleoside triphosphate oxoguanine- hydrolases); <br>Nudix
triphosphatase) (EC proteins (nucleoside 3.6.1.--)/Thiamin-
triphosphate hydrolases) phosphate pyrophosphorylase-like protein
fig|6666666.60966.peg.605 CDS 557210 556338 -2 - 873 putative
ATP/GTP- -none- D23_1c0605 Neut_0654 binding protein
fig|6666666.60966.peg.606 CDS 558441 557212 -3 - 1230 Glutamate N-
Arginine Biosynthesis-- D23_1c0607 Neut_0655 acetyltransferase (EC
gjo; <br>Arginine 2.3.1.35)/N- Biosynthesis--gjo;
acetylglutamate <br>Arginine synthase (EC 2.3.1.1)
Biosynthesis extended; <br>Arginine Biosynthesis extended
fig|6666666.60966.peg.607 CDS 558602 559015 2 + 414 FIG136845:
Rhodanese- Glutaredoxin 3 D23_1c0608 Neut_0656 related containing
cluster sulfurtransferase fig|6666666.60966.peg.608 CDS 559045
559302 1 + 258 Glutaredoxin 3 (Grx3) Glutaredoxin 3 D23_1c0609
Neut_0657 containing cluster; <br>Glutaredoxins;
<br>Glutathione: Redox cycle fig|6666666.60966.peg.609 CDS
559377 559862 3 + 486 Protein export Glutaredoxin 3 D23_1c0610
Neut_0658 cytoplasm chaperone containing cluster protein (SecB,
maintains protein to be exported in unfolded state)
fig|6666666.60966.peg.610 CDS 559866 560345 3 + 480 FIG00859406:
-none- D23_1c0611 Neut_0659 hypothetical protein
fig|6666666.60966.peg.611 CDS 560342 561331 2 + 990
Glycerol-3-phosphate Glutaredoxin 3 D23_1c0612 Neut_0660
dehydrogenase containing cluster; [NAD(P)+] (EC 1.1.1.94)
<br>Glycerol and Glycerol-3-phosphate Uptake and Utilization;
<br>Glycerolipid and Glycerophospholipid Metabolism in
Bacteria fig|6666666.60966.peg.612 CDS 561519 561791 3 + 273
DNA-binding protein DNA structural proteins, D23_1c0613 Neut_0661
HU-beta bacterial fig|6666666.60966.peg.614 CDS 562230 564023 3 +
1794 Peptidyl-prolyl cis-trans Peptidyl-prolyl cis-trans D23_1c0616
Neut_0662 isomerase PpiD (EC isomerase 5.2.1.8)
fig|6666666.60966.peg.615 CDS 564844 564050 -1 - 795
Enoyl-[acyl-carrier- Fatty Acid Biosynthesis D23_1c0617 Neut_0663
protein] reductase FASII [NADH] (EC 1.3.1.9)
fig|6666666.60966.peg.616 CDS 565168 564959 -1 - 210 hypothetical
protein -none- D23_1c0618 NA fig|6666666.60966.peg.617 CDS 565170
567587 3 + 2418 Transcription accessory CBSS-243265.1.peg.198;
D23_1c0619 Neut_0664 protein (S1 RNA-binding
<br>Transcription domain) factors bacterial
fig|6666666.60966.peg.618 CDS 567598 567975 1 + 378 hypothetical
protein -none- D23_1c0620 Neut_0682 fig|6666666.60966.peg.619 CDS
567977 568255 2 + 279 hypothetical protein -none- D23_1c0621
Neut_0682 fig|6666666.60966.peg.621 CDS 568500 568871 3 + 372
hypothetical protein -none- D23_1c0622 Neut_0683
fig|6666666.60966.peg.622 CDS 569150 568989 -2 - 162 hypothetical
protein -none- D23_1c0623 Neut_0684 fig|6666666.60966.peg.623 CDS
570485 569238 -2 - 1248 Mobile element protein -none- D23_1c0624
Neut_0357 fig|6666666.60966.peg.624 CDS 571236 570577 -3 - 660
N-hydroxyarylamine O- -none- D23_1c0626 Neut_0684 acetyltransferase
(EC 2.3.1.118) fig|6666666.60966.peg.625 CDS 572209 571295 -1 - 915
Permease of the Queuosine-Archaeosine D23_1c0627 Neut_0685
drug/metabolite Biosynthesis transporter (DMT) superfamily
fig|6666666.60966.peg.626 CDS 573622 572339 -1 - 1284 TRAP
dicarboxylate TRAP Transporter D23_1c0628 Neut_0686 transporter,
DctM unknown substrate 6 subunit, unknown substrate 6
fig|6666666.60966.peg.627 CDS 574259 573705 -2 - 555 TRAP
dicarboxylate TRAP Transporter D23_1c0629 Neut_0687 transporter,
DctQ unknown substrate 6 subunit, unknown substrate 6
fig|6666666.60966.peg.628 CDS 575698 574334 -1 - 1365 TldE protein,
part of Putative TldE-TldD D23_1c0630 Neut_0688 TldE/TldD
proteolytic proteolytic complex complex fig|6666666.60966.peg.629
CDS 575950 576474 1 + 525 FIG138315: Putative Putative TldE-TldD
D23_1c0632 Neut_0689 alpha helix protein proteolytic complex
fig|6666666.60966.peg.630 CDS 576475 576609 1 + 135 hypothetical
protein -none- D23_1c0633 NA fig|6666666.60966.peg.631 CDS 576740
577006 2 + 267 FIG00859002: -none- D23_1c0635 Neut_0690
hypothetical protein fig|6666666.60966.peg.632 CDS 577046 577804 2
+ 759 Exodeoxyribonuclease DNA repair, bacterial D23_1c0636
Neut_0691 III (EC 3.1.11.2) fig|6666666.60966.peg.633 CDS 577801
579195 1 + 1395 AmpG permease Recycling of D23_1c0637 Neut_0692
Peptidoglycan Amino Acids fig|6666666.60966.peg.636 CDS 580217
579867 -2 - 351 Cytochrome O Terminal cytochrome O D23_1c0638
Neut_0694 ubiquinol oxidase ubiquinol oxidase; subunit IV (EC
1.10.3.--) <br>Terminal cytochrome oxidases
fig|6666666.60966.peg.637 CDS 580885 580214 -1 - 672 Cytochrome O
Terminal cytochrome O D23_1c0639 Neut_0695 ubiquinol oxidase
ubiquinol oxidase; subunit III (EC 1.10.3.--) <br>Terminal
cytochrome oxidases fig|6666666.60966.peg.638 CDS 582993 580882 -3
- 2112 Cytochrome O Terminal cytochrome O D23_1c0640 Neut_0696
ubiquinol oxidase ubiquinol oxidase; subunit 1 (EC 1.10.3.--)
<br>Terminal cytochrome oxidases fig|6666666.60966.peg.639
CDS 583998 582997 -3 - 1002 Cytochrome O Terminal cytochrome O
D23_1c0641 Neut_0697 ubiquinol oxidase ubiquinol oxidase; subunit
II (EC 1.10.3.--) <br>Terminal cytochrome oxidases
fig|6666666.60966.peg.640 CDS 585484 584237 -1 - 1248 Mobile
element protein -none- D23_1c0642 Neut_0357
fig|6666666.60966.peg.641 CDS 585502 585633 1 + 132 patatin family
protein -none- D23_1c0643 Neut_1317 fig|6666666.60966.peg.642 CDS
585643 586530 1 + 888 UTP--glucose-1- -none- D23_1c0644 Neut_0698
phosphate uridylyltransferase (EC 2.7.7.9)
fig|6666666.60966.peg.643 CDS 586705 587817 1 + 1113 FIG00859666:
-none- D23_1c0645 Neut_0699 hypothetical protein
fig|6666666.60966.peg.644 CDS 587837 589201 2 + 1365
Succinate-semialdehyde -none- D23_1c0646 Neut_0700 dehydrogenase
[NAD] (EC 1.2.1.24); Succinate- semialdehyde dehydrogenase [NADP+]
(EC 1.2.1.16) fig|6666666.60966.peg.645 CDS 589224 590942 3 + 1719
InterPro IPR001440 -none- D23_1c0647 Neut_0701 COGs COG0457
fig|6666666.60966.peg.646 CDS 592871 591033 -2 - 1839
Long-chain-fatty-acid-- Biotin biosynthesis; D23_1c0648 Neut_0702
CoA ligase (EC 6.2.1.3) <br>Biotin synthesis cluster;
<br>Fatty acid metabolism cluster fig|6666666.60966.peg.647
CDS 595204 592868 -1 - 2337 Butyryl-CoA -none- D23_1c0649 Neut_0703
dehydrogenase (EC 1.3.99.2) fig|6666666.60966.peg.648 CDS 595489
595223 -1 - 267 hypothetical protein -none- D23_1c0650 Neut_0704
fig|6666666.60966.peg.649 CDS 596053 595673 -1 - 381 Putative
membrane -none- D23_1c0651 Neut_0705 protein
fig|6666666.60966.peg.650 CDS 596962 596099 -1 - 864 Pirin -none-
D23_1c0652 Neut_0706 fig|6666666.60966.peg.651 CDS 597098 598030 2
+ 933 Transcriptional -none- D23_1c0653 Neut_0707 regulator, LysR
family fig|6666666.60966.peg.652 CDS 598202 599338 2 + 1137
hypothetical protein -none- D23_1c0655 Neut_0708
fig|6666666.60966.peg.653 CDS 599418 599657 3 + 240 Flavodoxin
reductases Anaerobic respiratory D23_1c0656 Neut_0709
(ferredoxin-NADPH reductases reductases) family 1
fig|6666666.60966.peg.654 CDS 599689 600114 1 + 426 Flavodoxin
reductases Anaerobic respiratory D23_1c0657 Neut_0709
(ferredoxin-NADPH reductases reductases) family 1
fig|6666666.60966.peg.655 CDS 601243 600251 -1 - 993 Multicopper
oxidase Copper homeostasis D23_1c0658 Neut_0710
fig|6666666.60966.peg.656 CDS 602188 601454 -1 - 735 FIG00859807:
-none- D23_1c0659 Neut_0711 hypothetical protein
fig|6666666.60966.peg.657 CDS 602534 602346 -2 - 189 hypothetical
protein -none- D23_1c0660 Neut_0712
fig|6666666.60966.peg.658 CDS 602837 602700 -2 - 138 Putative
NAD(P)- -none- D23_1c0661 Neut_0990 dependent oxidoreductase EC-
YbbO fig|6666666.60966.peg.659 CDS 603148 602882 -1 - 267 ABC-type
multidrug CBSS-196164.1.peg.1690 D23_1c0662 Neut_0713 transport
system, permease component fig|6666666.60966.peg.660 CDS 603362
605239 2 + 1878 1,4-alpha-glucan -none- D23_1c0663 Neut_0714
branching enzyme (EC 2.4.1.18) fig|6666666.60966.peg.661 CDS 605497
605619 1 + 123 Glutathione peroxidase Glutathione: Redox cycle
D23_1c0664 Neut_0715 (EC 1.11.1.9) fig|6666666.60966.peg.662 CDS
607768 605882 -1 - 1887 TonB-dependent hemin, Ton and Tol transport
D23_1c0665 Neut_0716 ferrichrome receptor systems
fig|6666666.60966.peg.663 CDS 609583 607862 -1 - 1722 hypothetical
protein -none- D23_1c0666 Neut_0717 fig|6666666.60966.peg.664 CDS
610957 609656 -1 - 1302 Membrane protein -none- D23_1c0667
Neut_0718 involved in colicin uptake fig|6666666.60966.peg.665 CDS
611184 612413 3 + 1230 FIG00858430: -none- D23_1c0668 Neut_0719
hypothetical protein fig|6666666.60966.peg.666 CDS 612533 615022 2
+ 2490 TonB-dependent Ton and Tol transport D23_1c0669 Neut_0720
receptor systems fig|6666666.60966.peg.667 CDS 615143 615012 -2 -
132 hypothetical protein -none- D23_1c0670 NA
fig|6666666.60966.peg.668 CDS 615337 617457 1 + 2121 TonB-dependent
Ton and Tol transport D23_1c0672 Neut_0721 receptor systems
fig|6666666.60966.peg.669 CDS 617524 618762 1 + 1239 putative
signal peptide -none- D23_1c0673 Neut_0722 protein
fig|6666666.60966.peg.670 CDS 618762 619262 3 + 501 InterPro
IPR000063 -none- D23_1c0674 Neut_0723 COGs COG0526
fig|6666666.60966.peg.671 CDS 619459 621978 1 + 2520 Enoyl-CoA
hydratase Acetyl-CoA fermentation D23_1c0675 Neut_0724 (EC
4.2.1.17)/3,2- to Butyrate; <br>Acetyl- trans-enoyl-CoA CoA
fermentation to isomerase (EC 5.3.3.8)/ Butyrate; <br>Butanol
3-hydroxyacyl-CoA Biosynthesis; dehydrogenase (EC
<br<Butyrate 1.1.1.35) metabolism cluster; <br>Butyrate
metabolism cluster; <br>Fatty acid metabolism cluster;
<br>Fatty acid metabolism cluster;
<br>Polyhydroxybutyrate metabolism;
<br>Polyhydroxybutyrate metabolism fig|6666666.60966.peg.672
CDS 622043 623245 2 + 1203 3-ketoacyl-CoA thiolase Acetyl-CoA
fermentation D23_1c0676 Neut_0725 (EC 2.3.1.16) @ Acetyl- to
Butyrate; <br>Biotin CoA acetyltransferase biosynthesis;
<br>Biotin (EC 2.3.1.9) synthesis cluster; <br>Butanol
Biosynthesis; <br>Butyrate metabolism cluster;
<br>Fatty acid metabolism cluster; <br>Isoprenoid
Biosynthesis; <br>Polyhydroxybutyrate metabolism;
<br>Polyhydroxybutyrate metabolism fig|6666666.60966.peg.673
CDS 623639 623301 -2 - 339 FIG00859796: -none- D23_1c0677 Neut_0726
hypothetical protein fig|6666666.60966.peg.674 CDS 623711 623827 2
+ 117 hypothetical protein -none- D23_1c0678 NA
fig|6666666.60966.peg.675 CDS 624186 624479 3 + 294 Mobile element
protein -none- D23_1c0680 Neut_1719 fig|6666666.60966.peg.676 CDS
624578 625456 2 + 879 Mobile element protein -none- D23_1c0681
Neut_1720 fig|6666666.60966.peg.677 CDS 626009 625605 -2 - 405
hypothetical protein -none- D23_1c0682 NA fig|6666666.60966.peg.678
CDS 626270 628669 2 + 2400 Predicted hydrolase of -none- D23_1c0684
Neut_0728 the metallo-beta- lactamase superfamily, clustered with
KDO2- Lipid A biosynthesis genes fig|6666666.60966.peg.679 CDS
628866 629183 3 + 318 Flagellar transcriptional Flagellum
D23_1c0685 Neut_0729 activator FlhD fig|6666666.60966.peg.680 CDS
629210 629785 2 + 576 Flagellar transcriptional Flagellum
D23_1c0686 Neut_0730 activator FlhC fig|6666666.60966.peg.681 CDS
630020 631549 2 + 1530 Proposed peptidoglycan Peptidoglycan lipid
II D23_1c0687 Neut_0731 lipid II flippase MurJ flippase
fig|6666666.60966.peg.683 CDS 633437 632277 -2 - 1161 Outer
membrane Lipopolysaccharide D23_1c0688 Neut_0732 protein NlpB,
assembly lipoprotein component of the protein assembly complex
(forms a complex with YaeT, YfiO, and YfgL); Lipoprotein-34
precursor fig|6666666.60966.peg.684 CDS 634289 633447 -2 - 843
Dihydrodipicolinate -none- D23_1c0689 Neut_0733 synthase (EC
4.2.1.52) fig|6666666.60966.peg.685 CDS 637007 634416 -2 - 2592
ClpB protein Protein chaperones; D23_1c0690 Neut_0734
<br>Proteolysis in bacteria, ATP-dependent
fig|6666666.60966.peg.686 CDS 637484 637326 -2 - 159 hypothetical
protein -none- D23_1c0693 NA fig|6666666.60966.peg.687 CDS 638994
637501 -3 - 1494 Ferredoxin-dependent Ammonia assimilation;
D23_1c0694 Neut_0735 glutamate synthase (EC <br>Glutamine,
1.4.7.1) Glutamate, Aspartate and Asparagine Biosynthesis
fig|6666666.60966.peg.688 CDS 639034 639930 1 + 897 Quinolinate
Mycobacterium D23_1c0695 NA phosphoribosyltransferase virulence
operon [decarboxylating] possibly involved in (EC 2.4.2.19)
quinolinate biosynthesis; <br>NAD and NADP cofactor
biosynthesis global fig|6666666.60966.peg.689 CDS 641903 640635 -2
- 1269 Flagellar hook-length Flagellum D23_1c0696 Neut_0740 control
protein FliK fig|6666666.60966.peg.690 CDS 642413 641961 -2 - 453
Flagellar protein FliJ Flagellum D23_1c0697 Neut_0741
fig|6666666.60966.peg.691 CDS 643836 642430 -3 - 1407
Flagellum-specific ATP Flagellar motility; D23_1c0698 Neut_0742
synthase Flil <br>Flagellum fig|6666666.60966.peg.692 CDS
644577 643858 -3 - 720 Flagellar assembly Flagellum D23_1c0699
Neut_0743 protein FliH fig|6666666.60966.peg.693 CDS 645764 644769
-2 - 996 Flagellar motor switch Flagellum D23_1c0700 Neut_0744
protein FliG fig|6666666.60966.peg.694 CDS 647397 645754 -3 - 1644
Flagellar M-ring protein Flagellum D23_1C0701 Neut_0745 FliF
fig|6666666.60966.peg.695 CDS 647548 647402 -1 - 147 hypothetical
protein -none- D23_1c0702 NA fig|6666666.60966.peg.696 CDS 647628
648872 3 + 1245 Flagellar sensor Flagellum D23_1c0703 Neut_0746
histidine kinase FleS fig|6666666.60966.peg.697 CDS 648876 650189 3
+ 1314 InterPro -none- D23_1c0704 Neut_0747
IPR001789:IPR002078:IPR002197: IPR003593 COGs COG2204
fig|6666666.60966.peg.698 CDS 650217 650546 3 + 330 Flagellar
hook-basal Flagellum; <br>Flagellum D23_1c0705 Neut_0748 body
complex protein in Campylobacter FliE fig|6666666.60966.peg.699 CDS
650581 651390 1 + 810 FIG00858443: -none- D23_1c0706 Neut_0749
hypothetical protein fig|6666666.60966.peg.700 CDS 651752 651411 -2
- 342 Flagellar biosynthesis Flagellar motility; D23_1c0707
Neut_0750 protein FlhB <br>Flagellum
fig|6666666.60966.peg.701 CDS 652764 651739 -3 - 1026 FIG00726091:
-none- D23_1c0708 Neut_0751 hypothetical protein
fig|6666666.60966.peg.702 CDS 652766 652948 2 + 183 hypothetical
protein -none- D23_1c0709 NA fig|6666666.60966.peg.703 CDS 653125
653517 1 + 393 hypothetical protein -none- D23_1c0710 Neut_2449
fig|6666666.60966.peg.704 CDS 653664 653810 3 + 147 Mobile element
protein -none- D23_1c0711 Neut_1756 fig|6666666.60966.peg.705 CDS
654316 653858 -1 - 459 Cytochrome c family -none- D23_1c0712
Neut_0754 protein fig|6666666.60966.peg.706 CDS 654869 654345 -2 -
525 CopG protein Copper homeostasis D23_1c0713 Neut_0755
fig|6666666.60966.peg.707 CDS 655268 656209 2 + 942
tRNA(Cytosine32)-2- CBSS- D23_1c0714 Neut_0756 thiocytidine
synthetase 326442.4.peg.1852; <br>tRNA modification Bacteria
fig|6666666.60966.peg.708 CDS 657180 656236 -3 - 945 Lipoate
synthase Lipoic acid metabolism; D23_1c0715 Neut_0757
<br>Lipoic acid synthesis cluster; <br>Possible RNA
degradation cluster fig|6666666.60966.peg.709 CDS 657847 657170 -1
- 678 Octanoate-[acyl-carrier- Lipoic acid metabolism; D23_1c0716
Neut_0758 protein]-protein-N- <br>Lipoic acid synthesis
octanoyltransferase cluster fig|6666666.60966.peg.710 CDS 658198
657935 -1 - 264 Proposed lipoate Lipoicacid metabolism; D23_1c0717
Neut_0759 regulatory protein YbeD <br>Lipoic acid synthesis
cluster fig|6666666.60966.peg.711 CDS 659068 658208 -1 - 861
D-alanine Pyruvate Alanine Serine D23_1c0718 Neut_0760
aminotransferase (EC Interconversions 2.6.1.21)
fig|6666666.60966.peg.712 CDS 660251 659088 -2 - 1164
D-alanyl-D-alanine CBSS-84588.1.peg.1247; D23_1c0719 Neut_0761
carboxypeptidase (EC <br>Metallocarboxypeptidases 3.4.16.4)
(EC 3.4.17.--); <br>Murein Hydrolases;
<br>Peptidoglycan Biosynthesis fig|6666666.60966.peg.713 CDS
660353 660787 2 + 435 LSU ribosomal protein -none- D23_1c0720
Neut_0762 L13p (L13Ae) fig|6666666.60966.peg.714 CDS 660799 661191
1 + 393 SSU ribosomal protein -none- D23_1c0721 Neut_0763 S9p
(S16e) fig|6666666.60966.peg.715 CDS 661324 662352 1 + 1029
N-acetyl-gamma- Arginine Biosynthesis-- D23_1c0722 Neut_0764
glutamyl-phosphate gjo; <br>Arginine reductase (EC 1.2.1.38)
Biosynthesis extended fig|6666666.60966.peg.716 CDS 662454 663221 3
+ 768 putative integral -none- D23_1c0723 Neut_0765 membrane
protein fig|6666666.60966.peg.717 CDS 663202 663627 1 + 426
Integral membrane -none- D23_1c0724 Neut_0766 protein CcmA involved
in cell shape determination fig|6666666.60966.peg.718 CDS 665316
663655 -3 - 1662 DNA repair protein DNA repair, bacterial
D23_1c0725 Neut_0767 RecN fig|6666666.60966.peg.719 CDS 666357
665326 -3 - 1032 NAD kinase (EC NAD and NADP cofactor D23_1c0726
Neut_0768 2.7.1.23) biosynthesis global fig|6666666.60966.peg.720
CDS 666433 667449 1 + 1017 Heat-inducible GroEL GroES;
<br>Heat D23_1c0727 Neut_0769 transcription repressor shock
dnaK gene cluster HrcA extended fig|6666666.60966.peg.721 CDS
667469 668566 2 + 1098 Ferrochelatase, Heme and Siroheme D23_1c0728
Neut_0770 protoheme ferro-lyase Biosynthesis (EC 4.99.1.1)
fig|6666666.60966.peg.722 CDS 668678 669469 2 + 792 Zn-dependent
protease -none- D23_1c0729 Neut_0771
with chaperone function PA4632 fig|6666666.60966.peg.723 CDS 669589
670461 1 + 873 Phosphoribulokinase Calvin-Benson cycle D23_1c0730
Neut_0772 (EC 2.7.1.19) fig|6666666.60966.peg.724 CDS 670525 672771
1 + 2247 ATP-dependent DNA DNA repair, bacterial D23_1c0731
Neut_0773 helicase UvrD/PcrA UvrD and related helicases
fig|6666666.60966.peg.725 CDS 673569 672778 -3 - 792 Possible
-none- D23_1c0732 Neut_0774 transmembrane protein
fig|6666666.60966.peg.726 CDS 674610 673660 -3 - 951 Homoserine
kinase (EC CBSS- D23_1c0733 Neut_0775 2.7.1.39) 269482.1.peg.1294;
<br>Methionine Biosynthesis; <br>Threonine and
Homoserine Biosynthesis fig|6666666.60966.peg.727 CDS 674585 674716
2 + 132 hypothetical protein -none- D23_1c0734 NA
fig|6666666.60966.peg.728 CDS 675030 674704 -3 - 327 FIG00858562:
-none- D23_1c0735 Neut_0776 hypothetical protein
fig|6666666.60966.peg.729 CDS 675190 674996 -1 - 195 hypothetical
protein -none- D23_1c0736 NA fig|6666666.60966.peg.730 CDS 675866
675147 -2 - 720 FIG00859241: -none- D23_1c0737 Neut_0777
hypothetical protein fig|6666666.60966.peg.731 CDS 675882 678602 3
+ 2721 DNA polymerase I (EC DNA Repair Base D23_1c0738 Neut_0778
2.7.7.7) Excision fig|6666666.60966.peg.732 CDS 678725 679912 2 +
1188 Fatty acid desaturase -none- D23_1c0739 Neut_0779 (EC
1.14.19.1); Delta-9 fatty acid desaturase (EC 1.14.19.1)
fig|6666666.60966.peg.733 CDS 680149 679994 -1 - 156 LSU ribosomal
protein -none- D23_1c0740 Neut_0780 L33p @ LSU ribosomal protein
L33p, zinc- independent fig|6666666.60966.peg.734 CDS 680390 680190
-2 - 201 LSU ribosomal protein -none- D23_1c0741 Neut_0781 L28p
fig|6666666.60966.peg.735 CDS 681169 680495 -1 - 675 DNA repair
protein Bacterial cell division D23_1c0742 Neut_0782 RadC cluster;
<br>DNA repair, bacterial fig|6666666.60966.peg.736 CDS
681339 682508 3 + 1170 Phosphopantothenoylcysteine Coenzyme A
D23_1c0743 Neut_0783 decarboxylase Biosynthesis; (EC 4.1.1.36)/
<br>Coenzyme A Phosphopantothenoylcysteine Biosynthesis
synthetase (EC 6.3.2.5) fig|6666666.60966.peg.737 CDS 682518 682967
3 + 450 Deoxyuridine 5'- Housecleaning D23_1c0744 Neut_0784
triphosphate nucleoside triphosphate nucleotidohydrolase (EC
pyrophosphatases; 3.6.1.23) <br>Nudix proteins (nucleoside
triphosphate hydrolases) fig|6666666.60966.peg.738 CDS 682961
683386 2 + 426 exported protein -none- D23_1c0745 Neut_0785
fig|6666666.60966.peg.739 CDS 685816 683759 -1 - 2058
Pyrophosphate- Phosphate metabolism D23_1c0746 Neut_0786 energized
proton pump (EC 3.6.1.1) fig|6666666.60966.peg.740 CDS 687229
685970 -1 - 1260 6-phosphofructokinase Glycolysis and D23_1c0747
Neut_0787 (EC 2.7.1.11) Gluconeogenesis fig|6666666.60966.peg.741
CDS 687933 687400 -3 - 534 Adenylate kinase (EC Purine conversions
D23_1c0748 NA 2.7.4.3) fig|6666666.60966.peg.742 CDS 688328 689359
2 + 1032 RecA protein DNA repair, bacterial; D23_1c0749 Neut_0789
<br>DNA repair system including RecA, MutS and a hypothetical
protein; <br>RecA and RecX fig|6666666.60966.peg.743 CDS
689362 689802 1 + 441 Regulatory protein RecX DNA repair system
D23_1c0750 Neut_0790 including RecA, MutS and a hypothetical
protein; <br>RecA and RecX fig|6666666.60966.peg.744 CDS
689820 692411 3 + 2592 Alanyl-tRNA synthetase Cluster containing
D23_1c0751 Neut_0791 (EC 6.1.1.7) Alanyl-tRNA synthetase;
<br>tRNA aminoacylation, Ala fig|6666666.60966.peg.745 CDS
692450 693403 2 + 954 Thioredoxin reductase Thioredoxin-disulfide
D23_1c0752 Neut_0792 (EC 1.8.1.9) reductase; <br>pyrimidine
conversions fig|6666666.60966.peg.746 CDS 693409 6939991 1 + 591
Smr domain -none- D23_1c0753 Neut_0793 fig|6666666.60966.peg.747
CDS 694203 694349 3 + 147 Carbonic anhydrase (EC Zinc regulated
enzymes D23_1c0754 Neut_0794 4.2.1.1) fig|6666666.60966.peg.750 CDS
695056 695208 1 + 153 hypothetical protein -none- D23_1c0755
Neut_1255 fig|6666666.60966.peg.751 CDS 695216 695383 2 + 168
hypothetical protein -none- D23_1c0756 Neut_2449
fig|6666666.60966.peg.752 CDS 695522 695986 2 + 465 Mobile element
protein -none- D23_1c0758 Neut_1256 fig|6666666.60966.peg.753 CDS
696281 696072 -2 - 210 Chemotaxis regulator- Flagellar motility
D23_1c0759 Neut_0796 transmits chemoreceptor signals to flagelllar
motor components CheY fig|6666666.60966.peg.754 CDS 696491 696619 2
+ 129 hypothetical protein -none- D23_1c0760 Neut_0797
fig|6666666.60966.peg.755 CDS 696639 696812 3 + 174 Mobile element
protein -none- D23_1c0760 Neut_0797 fig|6666666.60966.peg.756 CDS
696806 696934 2 + 129 Mobile element protein -none- D23_1c0761 NA
fig|6666666.60966.peg.757 CDS 697179 698426 3 + 1248 Mobile element
protein -none- D23_1c0762 Neut_0357 fig|6666666.60966.peg.758 CDS
698760 700454 3 + 1695 NADH dehydrogenase, Respiratory Complex I
D23_1c0763 Neut_0799 subunit 5 fig|6666666.60966.peg.759 CDS 700473
701258 3 + 786 hypothetical protein -none- D23_1c0765 Neut_0800
fig|6666666.60966.peg.760 CDS 701243 704371 2 + 3129 Hypothetical
CO2 uptake, D23_1c0766 Neut_0801 transmembrane protein carboxysome;
coupled to NADH- <br>Respiratory ubiquinone Complex I
oxidoreductase chain 5 homolog fig|6666666.60966.peg.761 CDS 704368
704694 1 + 327 Nitrogen regulatory Ammonia assimilation D23_1c0767
Neut_0802 protein P-II fig|6666666.60966.peg.762 CDS 704850 705059
3 + 210 hypothetical protein -none- D23_1c0768 Neut_0800
fig|6666666.60966.peg.763 CDS 705044 708184 2 + 3141 Hypothetical
CO2 uptake, D23_1c0769 Neut_0801 transmembrane protein carboxysome;
coupled to NADH- <br>Respiratory ubiquinone Complex I
oxidoreductase chain 5 homolog fig|6666666.60966.peg.764 CDS 708181
708507 1 + 327 Nitrogen regulatory Ammonia assimilation D23_1c0770
Neut_0802 protein P-II fig|6666666.60966.peg.765 CDS 709429 708509
-1 - 921 RuBisCO operon CO2 uptake, D23_1c0771 Neut_0803
transcriptional carboxysome regulator CbbR
fig|6666666.60966.peg.766 CDS 709628 711049 2 + 1422 Ribulose
bisphosphate CO2 uptake, D23_1c0772 Neut_0804 carboxylase large
chain carboxysome; (EC 4.1.1.39) <br>Calvin-Benson cycle;
<br>Photorespiration (oxidative C2 cycle)
fig|6666666.60966.peg.767 CDS 711134 711460 2 + 327 Ribulose
bisphosphate CO2 uptake, D23_1c0773 Neut_0805 carboxylase small
chain carboxysome; (EC 4.1.1.39) <br>Calvin-Benson cycle;
<br>Photorespiration (oxidative C2 cycle)
fig|6666666.60966.peg.768 CDS 711860 711645 -2 - 216 hypothetical
protein -none- D23_1c0774 Neut_0806 fig|6666666.60966.peg.769 CDS
711868 714264 1 + 2397 carboxysome shell CO2 uptake, D23_1c0774
Neut_0806 protein CsoS2 carboxysome fig|6666666.60966.peg.770 CDS
714275 715804 2 + 1530 carboxysome shell CO2 uptake, D23_1c0775
Neut_0807 protein CsoS3 carboxysome fig|6666666.60966.peg.771 CDS
715825 716082 1 + 258 putative carboxysome CO2 uptake, D23_1c0776
Neut_0808 peptide A carboxysome fig|6666666.60966.peg.772 CDS
716082 716330 3 + 249 putative carboxysome CO2 uptake, D23_1c0777
Neut_0809 peptide B carboxysome fig|6666666.60966.peg.773 CDS
716439 716735 3 + 297 carboxysome shell CO2 uptake, D23_1c0778
Neut_0810 protein CsoS1 carboxysome fig|6666666.60966.peg.774 CDS
716777 717124 2 + 348 carboxysome shell CO2 uptake, D23_1c0779
Neut_0811 protein CsoS1 carboxysome fig|6666666.60966.peg.775 CDS
717145 717567 1 + 423 bacterioferritin possible -none- D23_1c0780
Neut_0812 associated with carboxysome fig|6666666.60966.peg.776 CDS
717576 717842 3 + 267 Possible pterin-4 alpha- CO2 uptake,
D23_1c0781 Neut_0813 carbinolamine carboxysome dehydratase-like
protein fig|6666666.60966.peg.777 CDS 717911 718483 2 + 573
Chromosome (plasmid) Bacterial Cell Division; D23_1c0782 Neut_0814
partitioning protein <br>Bacterial ParA Cytoskeleton;
<br>Cell Division Subsystem including YidCD; <br>RNA
modification and chromosome partitioning cluster
fig|6666666.60966.peg.778 CDS 718480 718674 1 + 195 hypothetical
protein -none- D23_1c0783 NA fig|6666666.60966.peg.779 CDS 718681
719631 1 + 951 Rubisco activation CO2 uptake, D23_1c0784 Neut_0815
protein CbbQ carboxysome fig|6666666.60966.peg.780 CDS 719654
722014 2 + 2361 Rubisco activation CO2 uptake, D23_1c0785 Neut_0816
protein CbbO carboxysome fig|6666666.60966.peg.781 CDS 722027
722659 2 + 633 FIG00852745: -none- D23_1c0786 Neut_0817
hypothetical protein fig|6666666.60966.peg.782 CDS 722704 723528 1
+ 825 FIG00853400: -none- D23_1c0787 Neut_0818 hypothetical protein
fig|6666666.60966.peg.783 CDS 723822 723676 -3 - 147 Mobile element
protein -none- D23_1c0788 NA fig|6666666.60966.peg.784 CDS 723900
724055 3 + 156 hypothetical protein -none- D23_1c0790 NA
fig|6666666.60966.peg.785 CDS 724125 724304 3 + 180 Rubisco
activation CO2 uptake, D23_1c0791 NA protein CbbO carboxysome
fig|6666666.60966.peg.786 CDS 724415 724621 2 + 207 Rubisco
activation CO2 uptake, D23_1c0792 Neut_0816 protein CbbO
carboxysome fig|6666666.60966.peg.787 CDS 724700 724975 2 + 276
Nitric oxide reductase Denitrification; D23_1c0793 Neut_0816
activation protein NorD <br>Denitrifying reductase gene
clusters fig|6666666.60966.peg.788 CDS 724985 725104 2 + 120
hypothetical protein -none- D23_1c0794 Neut_0816
fig|6666666.60966.peg.789 CDS 725079 725336 3 + 258 Nitric oxide
reductase Denitrification; D23_1c0794 Neut_0816 activation protein
NorD <br>Denitrifying reductase gene clusters
fig|6666666.60966.peg.790 CDS 725493 725657 3 + 165 hypothetical
protein -none- D23_1c0795 Neut_0821 fig|6666666.60966.peg.791 CDS
727182 725782 -3 - 1401 FIG00861154: -none- D23_1c0796 Neut_1550
hypothetical protein fig|6666666.60966.peg.792 CDS 727830 727411 -3
- 420 FIG00859219: -none- D23_1c0797 Neut_0823 hypothetical protein
fig|6666666.60966.peg.793 CDS 729449 728481 -2 - 969 Octaprenyl
diphosphate Isoprenoid Biosynthesis; D23_1c0800 Neut_0825 synthase
(EC 2.5.1.90)/ <br>Isoprenoid Dimethylallyltransferase
Biosynthesis;
(EC 2.5.1.1)/(2E,6E)- <br>Isoprenoid farnesyl diphosphate
Biosynthesis: synthase (EC 2.5.1.10)/ Interconversions;
Geranylgeranyl <br>Isoprenoinds for diphosphate synthase
Quinones; (EC 2.5.1.29) <br>Isoprenoinds for Quinones;
<br>Isoprenoinds for Quinones; <br>Isoprenoinds for
Quinones; <br>Polyprenyl Diphosphate Biosynthesis;
<br>Polyprenyl Diphosphate Biosynthesis; <br>Polyprenyl
Diphosphate Biosynthesis fig|6666666.60966.peg.795 CDS 729633
730886 3 + 1254 Glutamyl-tRNA A Gammaproteobacteria D23_1c0801
Neut_0826 reductase (EC 1.2.1.70) Cluster Relating to Translation;
<br>Heme and Siroheme Biosynthesis fig|6666666.60966.peg.796
CDS 730883 731962 2 + 1080 Peptide chain release A
Gammaproteobacteria D23_1c0802 Neut_0827 factor 1 Cluster Relating
to Translation; <br>CBSS- 216600.3.peg.802;
<br>Translation termination factors bacterial
fig|6666666.60966.peg.797 CDS 731959 732840 1 + 882
Protein-N(5)-glutamine A Gammaproteobacteria D23_1c0803 Neut_0828
methyltransferase Cluster Relating to PrmC, methylates Translation;
<br>CBSS- polypeptide chain 216600.3.peg.802; release factors
RF1 and <br>Translation RF2 termination factors bacterial
fig|6666666.60966.peg.798 CDS 732995 733303 2 + 309
Glutaredoxin-related Glutaredoxins D23_1c0805 Neut_0829 protein
fig|6666666.60966.peg.799 CDS 733743 733324 -3 - 420 Putative
membrane -none- D23_1c0806 Neut_0830 protein
fig|6666666.60966.peg.800 CDS 734018 734161 2 + 144 hypothetical
protein -none- D23_1c0807 NA fig|6666666.60966.peg.801 CDS 734194
734826 1 + 633 Glutathione S- Glutathione: Non-redox D23_1c0808
Neut_0831 transferase (EC reactions 2.5.1.18)
fig|6666666.60966.peg.802 CDS 735097 735381 1 + 285 conserved
hypothetical -none- D23_1c0809 Neut_0832 protein
fig|6666666.60966.peg.803 CDS 735730 736488 1 + 759 hypothetical
protein -none- D23_1c0810 Neut_0833 fig|6666666.60966.peg.804 CDS
737600 736485 -2 - 1116 COGs COG1502 -none- D23_1c0811 Neut_0834
fig|6666666.60966.peg.805 CDS 738943 737585 -1 - 1359 hypothetical
protein -none- D23_1c0812 Neut_0835 fig|6666666.60966.peg.806 CDS
739386 739240 -3 - 147 hypothetical protein -none- D23_1c0813 NA
fig|6666666.60966.peg.807 CDS 740790 739585 -3 - 1206 DnaJ domain
protein -none- D23_1c0814 Neut_0836 fig|6666666.60966.peg.809 CDS
742340 741159 -2 - 1182 Putative -none- D23_1c0815 Neut_0837
aminotransferase fig|6666666.60966.peg.810 CDS 744454 742337 -1 -
2118 Conserved domain -none- D23_1c0816 Neut_0838 protein
fig|6666666.60966.peg.811 CDS 744823 744647 -1 - 177 hypothetical
protein -none- D23_1c0817 NA fig|6666666.60966.peg.812 CDS 745953
745228 -3 - 726 hypothetical protein -none- D23_1c0818 Neut_0840
fig|6666666.60966.peg.814 CDS 748473 746350 -3 - 2124 InterPro
IPR000209 -none- D23_1c0820 Neut_0841 COGs COG1404
fig|6666666.60966.peg.815 CDS 748862 749245 2 + 384 ApaG protein
EC49-61 D23_1c0822 Neut_0842 fig|6666666.60966.peg.816 CDS 749258
749992 2 + 735 Tetrapyrrole methylase -none- D23_1c0823 Neut_0843
family protein fig|6666666.60966.peg.817 CDS 751297 750077 -1 -
1221 Proton/glutamate Glutamate and D23_1c0824 Neut_0844 symport
protein @ Aspartate uptake in Sodium/glutamate Bacteria symport
protein fig|6666666.60966.peg.818 CDS 752156 751611 -2 - 546
Cytochrome c-type Biogenesis of c-type D23_1c0825 Neut_0845
biogenesis protein ResA cytochromes fig|6666666.60966.peg.819 CDS
754247 752304 -2 - 1944 Cytochrome c-type Biogenesis of c-type
D23_1c0826 Neut_0846 biogenesis protein cytochromes; DsbD,
protein-disulfide <br>Periplasmic disulfide reductase (EC
1.8.1.8) interchange fig|6666666.60966.peg.820 CDS 754631 754260 -2
- 372 Periplasmic divalent Copper homeostasis: D23_1c0827 Neut_0847
cation tolerance protein copper tolerance CutA
fig|6666666.60966.peg.821 CDS 754715 754909 2 + 195 FIG00859483:
-none- D23_1c0828 Neut_0848 hypothetical protein
fig|6666666.60966.peg.822 CDS 754952 755695 2 + 744 FIG00859295:
-none- D23_1c0829 Neut_0849 hypothetical protein
fig|6666666.60966.peg.823 CDS 756608 755733 -2 - 876 Staphylococcus
-none- D23_1c0830 Neut_0850 nuclease (SNase) domain
fig|6666666.60966.peg.824 CDS 756650 757549 2 + 900 Methionine ABC
Methionine D23_1c0831 Neut_0851 transporter ATP-binding
Biosynthesis; protein <br>Methionine Degradation
fig|6666666.60966.peg.825 CDS 757674 758384 3 + 711 Uncharacterized
ABC Lipopolysaccharide D23_1c0832 Neut_0852 transporter, permease
assembly component YrbE fig|6666666.60966.peg.826 CDS 758396 758863
2 + 468 Uncharacterized ABC Lipopolysaccharide D23_1c0833 Neut_0853
transporter, periplasmic assembly component YrbD
fig|6666666.60966.peg.827 CDS 758879 759496 2 + 618 Uncharacterized
ABC Lipopolysaccharide D23_1c0834 Neut_0854 transporter, auxiliary
assembly component YrbC fig|6666666.60966.peg.828 CDS 759503 759817
2 + 315 STAS domain -none- D23_1c0835 Neut_0855
fig|6666666.60966.peg.829 CDS 759879 760793 3 + 915 ABC-type
multidrug CBSS-196164.1.peg.1690 D23_1c0836 Neut_0856 transport
system, ATPase component fig|6666666.60966.peg.830 CDS 760790
761545 2 + 756 ABC-type multidrug CBSS-196164.1.peg.1690 D23_1c0837
Neut_0857 transport system, permease component
fig|6666666.60966.peg.831 CDS 761590 761844 1 + 255 YrbA protein
Broadly distributed D23_1c0838 Neut_0858 proteins not in subsystems
fig|6666666.60966.peg.832 CDS 763192 761900 -1 - 1293
Dihydrolipoamide Dehydrogenase D23_1c0839 Neut_0859
succinyltransferase complexes; <br>TCA component (E2) of 2-
Cycle oxoglutarate dehydrogenase complex (EC 2.3.1.61)
fig|6666666.60966.peg.833 CDS 766072 763214 -1 - 2859
2-oxoglutarate Dehydrogenase D23_1c0840 Neut_0860 dehydrogenase E1
complexes; <br>TCA component (EC 1.2.4.2) Cycle
fig|6666666.60966.peg.834 CDS 767529 766234 -3 - 1296 Citrate
synthase (si) (EC TCA Cycle D23_1c0841 Neut_0861 2.3.3.1)
fig|6666666.60966.peg.835 CDS 767808 767575 -3 - 234 YgfY COG2938
-none- D23_1c0842 Neut_0862 fig|6666666.60966.peg.836 CDS 768500
767805 -2 - 696 Succinate 5-FCL-like protein; D23_1c0843 Neut_0863
dehydrogenase iron- <br>Succinate sulfur protein (EC
dehydrogenase; 1.3.99.1) <br>TCA Cycle
fig|6666666.60966.peg.837 CDS 770059 768629 -1 - 1431 Threonine
synthase (EC Threonine and D23_1c0844 Neut_0864 4.2.3.1) Homoserine
Biosynthesis fig|6666666.60966.peg.839 CDS 771500 770184 -2 - 1317
Homoserine Methionine D23_1c0845 Neut_0865 dehydrogenase (EC
Biosynthesis; 1.1.1.3) <br>Threonine and Homoserine
Biosynthesis fig|6666666.60966.peg.840 CDS 772833 771607 -3 - 1227
Aspartate CBSS-216591.1.peg.168; D23_1c0846 Neut_0866
aminotransferase (EC <br>Glutamine, 2.6.1.1) Glutamate,
Aspartate and Asparagine Biosynthesis; <br>Threonine and
Homoserine Biosynthesis fig|6666666.60966.peg.841 CDS 773025 773147
3 + 123 hypothetical protein -none- D23_1c0847 NA
fig|6666666.60966.peg.842 CDS 773125 773508 1 + 384 Membrane
protein -none- D23_1c0848 Neut_0867 fig|6666666.60966.peg.843 CDS
773605 775980 1 + 2376 Phosphoenolpyruvate A Hypothetical that
D23_1c0849 Neut_0868 synthase (EC 2.7.9.2) Clusters with PEP
Synthase; <br>Glycolysis and Gluconeogenesis;
<br>Pyruvate metabolism I: anaplerotic reactions, PEP
fig|6666666.60966.peg.844 CDS 775985 776812 2 + 828 FIG137360: A
Hypothetical that D23_1c0850 Neut_0869 hypothetical protein
Clusters with PEP Synthase fig|6666666.60966.peg.845 CDS 777372
776854 -3 - 519 NLP/P60 -none- D23_1c0851 Neut_0870
fig|6666666.60966.peg.846 CDS 779204 777507 -2 - 1698
Glutaminyl-tRNA tRNA aminoacylation, D23_1c0852 Neut_0871
synthetase (EC 6.1.1.18) Glu and Gln fig|6666666.60966.peg.847 CDS
779394 779245 -3 - 150 hypothetical protein -none- D23_1c0853 NA
fig|6666666.60966.peg.848 CDS 779393 780991 2 + 1599 Lysyl-tRNA
synthetase tRNA aminoacylation, D23_1c0854 Neut_0872 (class II) (EC
6.1.1.6) Lys fig|6666666.60966.peg.849 CDS 781093 781749 1 + 657
FIG00858849: -none- D23_1c0855 Neut_0873 hypothetical protein
fig|6666666.60966.peg.850 CDS 781999 782385 1 + 387 hypothetical
protein -none- D23_1c0856 NA fig|6666666.60966.peg.851 CDS 782415
782747 3 + 333 Mobile element protein -none- D23_1c0857 NA
fig|6666666.60966.peg.852 CDS 782952 783485 3 + 534 hypothetical
protein -none- D23_1c0858 Neut_0875 fig|6666666.60966.peg.853 CDS
783597 783767 3 + 171 hypothetical protein -none- D23_1c0859 NA
fig|6666666.60966.peg.854 CDS 784671 784048 -3 - 624 Trp repressor
binding -none- D23_1c0860 Neut_0876 protein
fig|6666666.60966.peg.855 CDS 785041 784757 -1 - 285 Mobile element
protein -none- D23_1c0861 NA fig|6666666.60966.peg.857 CDS 787300
785558 -1 - 1743 Beta-glucosidase (EC -none- D23_1c0862 Neut_0879
3.2.1.21) fig|6666666.60966.peg.858 CDS 788430 787327 -3 - 1104
Mobile element protein -none- D23_1c0863 Neut_1278
fig|6666666.60966.peg.859 CDS 789557 789045 -2 - 513 Mobile element
protein -none- D23_1c0864 Neut_1624 fig|6666666.60966.peg.860 CDS
789894 789589 -3 - 306 Mobile element protein -none- D23_1c0865
Neut_1371 fig|6666666.60966.peg.861 CDS 790136 789951 -2 - 186
Mobile element protein -none- D23_1c0866 Neut_2500
fig|6666666.60966.peg.863 CDS 792236 790869 -2 - 1368 ATP-dependent
RNA ATP-dependent RNA D23_1c0869 Neut_0889 helicase RhlE helicases,
bacterial fig|6666666.60966.peg.865 CDS 794169 792502 -3 - 1668
ATPase components of -none- D23_1c0871 Neut_0890 ABC transporters
with duplicated ATPase domains fig|6666666.60966.peg.867 CDS 794389
794568 1 + 180 hypothetical protein -none- D23_1c0872 NA
fig|6666666.60966.peg.868 CDS 795019 795636 1 + 618 FIG123464: Cell
wall related cluster D23_1c0873 Neut_0891 Polysaccharide export
protein
fig|6666666.60966.peg.869 CDS 795679 797223 1 + 1545
Lipopolysaccharide Cell wall related cluster D23_1c0874 Neut_0892
biosynthesis chain length determinant protein
fig|6666666.60966.peg.870 CDS 797305 798243 1 + 939
Protein-tyrosine kinase Cell wall related cluster D23_1c0875
Neut_0893 (EC 2.7.1.112) fig|6666666.60966.peg.871 CDS 798243
799823 3 + 1581 Glycine-rich cell wall Cell wall related cluster
D23_1c0876 Neut_0894 structural protein precursor
fig|6666666.60966.peg.872 CDS 799837 800670 1 + 834 FIG022606: AAA
ATPase Cell wall related cluster D23_1c0877 Neut_0895
fig|6666666.60966.peg.873 CDS 800676 801515 3 + 840 FIG004655: Cell
wall related cluster D23_1c0878 Neut_0896 Polysaccharide
deacetylase fig|6666666.60966.peg.875 CDS 801827 802591 2 + 765
FIG070318: Cell wall related cluster D23_1c0879 Neut_0897
hypothetical protein fig|6666666.60966.peg.876 CDS 802597 803808 1
+ 1212 FIG137776: Cell wall related cluster D23_1c0880 Neut_0898
Glycosyltransferase fig|6666666.60966.peg.877 CDS 803877 805457 3 +
1581 Eight transmembrane Cell wall related cluster; D23_1c0881
Neut_0899 protein EpsH/EpsI <br>Cell wall related protein
cluster fig|6666666.60966.peg.878 CDS 805493 806635 2 + 1143
FIG040338: Glycosyl Cell wall related cluster D23_1c0882 Neut_0900
transferase fig|6666666.60966.peg.879 CDS 806677 808611 1 + 1935
Asparagine synthetase Cell wall related cluster; D23_1c0884
Neut_0901 [glutamine-hydrolyzing] <br>Glutamine, (EC 6.3.5.4)
AsnH Glutamate, Aspartate and Asparagine Biosynthesis
fig|6666666.60966.peg.880 CDS 808662 809654 3 + 993 FIG00859061:
-none- D23_1c0885 Neut_0902 hypothetical protein
fig|6666666.60966.peg.881 CDS 809654 810592 2 + 939 FIG00859041:
-none- D23_1c0886 Neut_0903 hypothetical protein
fig|6666666.60966.peg.882 CDS 810623 811849 2 + 1227 hypothetical
protein -none- D23_1c0887 Neut_0903 fig|6666666.60966.peg.883 CDS
812814 811852 -3 - 963 Mobile element protein -none- D23_1c0888
Neut_1746 fig|6666666.60966.peg.884 CDS 813957 813094 -3 - 864
Mobile element protein -none- D23_1c0889 Neut_2192
fig|6666666.60966.peg.885 CDS 814250 813954 -2 - 297 hypothetical
protein -none- D23_1c0890 Neut_2193 fig|6666666.60966.peg.887 CDS
814624 815706 1 + 1083 glycosyltransferase -none- D23_1c0891 NA
fig|6666666.60966.peg.888 CDS 817016 816339 -2 - 678 hypothetical
protein -none- D23_1c0892 NA fig|6666666.60966.peg.889 CDS 818253
817114 -3 - 1140 hypothetical protein -none- D23_1c0893 Neut_0906
fig|6666666.60966.peg.890 CDS 819313 818282 -1 - 1032 hypothetical
protein -none- D23_1c0894 Neut_2116 fig|6666666.60966.peg.891 CDS
820446 819313 -3 - 1134 hypothetical protein -none- D23_1c0895
Neut_0905 fig|6666666.60966.peg.892 CDS 821935 820481 -1 - 1455
hypothetical protein -none- D23_1c0896 Neut_0909
fig|6666666.60966.peg.893 CDS 823840 822074 -1 - 1767 Asparagine
synthetase Cyanophycin D23_1c0897 Neut_0910 [glutamine-hydrolyzing]
Metabolism; (EC 6.3.5.4) <br>Glutamate and Aspartate uptake
in Bacteria; <br>Glutamine, Glutamate, Aspartate and
Asparagine Biosynthesis fig|6666666.60966.peg.895 CDS 824361 825170
3 + 810 hypothetical protein -none- D23_1c0898 Neut_0911
fig|6666666.60966.peg.896 CDS 825186 826454 3 + 1269 hypothetical
protein -none- D23_1c0899 Neut_0912 fig|6666666.60966.peg.897 CDS
827356 826457 -1 - 900 hypothetical protein -none- D23_1c0900
Neut_0913 fig|6666666.60966.peg.898 CDS 827907 827404 -3 - 504 Low
molecular weight LMPTP YfkJ cluster; D23_1c0901 Neut_0914 protein
tyrosine <br>Protein deglycation phosphatase (EC 3.1.3.48)
fig|6666666.60966.peg.899 CDS 828032 829777 2 + 1746 ABC
transporter, fused -none- D23_1c0902 Neut_0915 permease and ATPase
domains fig|6666666.60966.peg.900 CDS 830559 829798 -3 - 762 Sulfur
carrier protein Thiamin biosynthesis D23_1c0903 Neut_0916
adenylyltransferase ThiF fig|6666666.60966.peg.901 CDS 832018
830588 -1 - 1431 Carboxyl-terminal Phosphoglycerate D23_1c0904
Neut_0917 protease (EC mutase protein family 3.4.21.102)
fig|6666666.60966.peg.902 CDS 833380 832100 -1 - 1281 Lipoprotein
NlpD Stationary phase repair D23_1c0905 Neut_0918 cluster
fig|6666666.60966.peg.903 CDS 834129 833380 -3 - 750
Phosphoglycerate Glycolysis and D23_1c0906 Neut_0919 mutase (EC
5.4.2.1) Gluconeogenesis; <br>Phosphoglycerate mutase protein
family fig|6666666.60966.peg.904 CDS 834328 835086 1 + 759
Triosephosphate CBSS- D23_1c0907 Neut_0920 isomerase (EC 5.3.1.1)
331978.3.peg.2915; <br>Calvin-Benson cycle;
<br>Glycolysis and Gluconeogenesis fig|6666666.60966.peg.905
CDS 835105 835470 1 + 366 Preprotein translocase
CBSS-331978.3.peg.2915 D23_1c0908 Neut_0921 subunit SecG (TC
3.A.5.1.1) fig|6666666.60966.peg.906 CDS 835677 836045 3 + 369 NADH
ubiquinone NADH ubiquinone D23_1c0910 Neut_0922 oxidoreductase
chain A oxidoreductase; (EC 1.6.5.3) <br>Respiratory Complex
I fig|6666666.60966.peg.907 CDS 836049 836525 3 + 477
NADH-ubiquinone NADH ubiquinone D23_1c0911 Neut_0923 oxidoreductase
chain B oxidoreductase; (EC 1.6.5.3) <br>Respiratory Complex
I fig|6666666.60966.peg.908 CDS 836535 837155 3 + 621
NADH-ubiquinone NADH ubiquinone D23_1c0912 Neut_0924 oxidoreductase
chain C oxidoreductase; (EC 1.6.5.3) <br>Respiratory Complex
I fig|6666666.60966.peg.909 CDS 837213 838466 3 + 1254
NADH-ubiquinone NADH ubiquinone D23_1c0913 Neut_0925 oxidoreductase
chain D oxidoreductase; (EC 1.6.5.3) <br>Respiratory Complex
I fig|6666666.60966.peg.910 CDS 838475 838951 2 + 477
NADH-ubiquinone NADH ubiquinone D23_1c0914 Neut_0926 oxidoreductase
chain E oxidoreductase; (EC 1.6.5.3) <br>Respiratory Complex
I fig|6666666.60966.peg.911 CDS 838948 840225 1 + 1278
NADH-ubiquinone NADH ubiquinone D23_1c0915 Neut_0927 oxidoreductase
chain F oxidoreductase; (EC 1.6.5.3) <br>Respiratory Complex
I fig|6666666.60966.peg.912 CDS 840287 842692 2 + 2406
NADH-ubiquinone NADH ubiquinone D23_1c0917 Neut_0928 oxidoreductase
chain G oxidoreductase; (EC 1.6.5.3) <br>Respiratory Complex
I fig|6666666.60966.peg.913 CDS 842717 843814 2 + 1098
NADH-ubiquinone NADH ubiquinone D23_1c0918 Neut_0929 oxidoreductase
chain H oxidoreductase; (EC 1.6.5.3) <br>Respiratory Complex
I fig|6666666.60966.peg.914 CDS 843832 844320 1 + 489
NADH-ubiquinone NADH ubiquinone D23_1c0919 Neut_0930 oxidoreductase
chain I oxidoreductase; (EC 1.6.5.3) <br>Respiratory Complex
I fig|6666666.60966.peg.915 CDS 844339 844944 1 + 606
NADH-ubiquinone NADH ubiquinone D23_1c0920 Neut_0931 oxidoreductase
chain J oxidoreductase; (EC 1.6.5.3) <br>Respiratory Complex
I fig|6666666.60966.peg.916 CDS 845000 845305 2 + 306
NADH-ubiquinone NADH ubiquinone D23_1c0921 Neut_0932 oxidoreductase
chain K oxidoreductase; (EC 1.6.5.3) <br>Respiratory Complex
I fig|6666666.60966.peg.917 CDS 845366 847312 2 + 1947
NADH-ubiquinone NADH ubiquinone D23_1c0922 Neut_0933 oxidoreductase
chain L oxidoreductase; (EC 1.6.5.3) <br>Respiratory Complex
I fig|6666666.60966.peg.918 CDS 847401 848882 3 + 1482
NADH-ubiquinone NADH ubiquinone D23_1c0923 Neut_0934 oxidoreductase
chain M oxidoreductase; (EC 1.6.5.3) <br>Respiratory Complex
I fig|6666666.60966.peg.919 CDS 848945 850390 2 + 1446
NADH-ubiquinone NADH ubiquinone D23_1c0924 Neut_0935 oxidoreductase
chain N oxidoreductase; (EC 1.6.5.3) <br>Respiratory Complex
I fig|6666666.60966.peg.920 CDS 851362 850412 -1 - 951 L-sorbosone
-none- D23_1c0925 Neut_0936 dehydrogenase fig|6666666.60966.peg.921
CDS 851619 853541 3 + 1923 Chaperone protein Protein chaperones
D23_1c0926 Neut_0937 HtpG fig|6666666.60966.peg.922 CDS 853878
854918 3 + 1041 WD40 domain protein -none- D23_1c0927 Neut_0938
beta Propeller fig|6666666.60966.peg.924 CDS 855176 855598 2 + 423
Mobile element protein -none- D23_1c0929 Neut_0939
fig|6666666.60966.peg.925 CDS 855805 858447 1 + 2643
Hopanoid-associated Hopanes D23_1c0930 Neut_0940 RND transporter,
HpnN fig|6666666.60966.peg.926 CDS 859079 858483 -2 - 597 DedA
protein Colicin V and Bacteriocin D23_1c0931 Neut_0941 Production
Cluster; <br>DedA family of inner membrane proteins;
<br>Uptake of selenate and selenite fig|6666666.60966.peg.928
CDS 861652 859424 -1 - 2229 Probable -none- D23_1c0933 Neut_0942
transmembrane protein fig|6666666.60966.peg.929 CDS 861629 861754 2
+ 126 hypothetical protein -none- D23_1c0934 NA
fig|6666666.60966.peg.930 CDS 861857 861720 -2 - 138 hypothetical
protein -none- D23_1c0935 NA fig|6666666.60966.peg.931 CDS 861928
862341 1 + 414 Protoporphyrinogen IX Heme and Siroheme D23_1c0936
Neut_0943 oxidase, novel form, Biosynthesis HemJ (EC 1.3.--.--)
fig|6666666.60966.peg.932 CDS 862893 862363 -3 - 531 Peptide
deformylase Bacterial RNA- D23_1c0937 Neut_0944 (EC 3.5.1.88)
metabolizing Zn- dependent hydrolases; <br>Translation
termination factors bacterial fig|6666666.60966.peg.933 CDS 863632
862886 -1 - 747 5'- -none- D23_1c0938 Neut_0945 methylthioadenosine
phosphorylase (EC 2.4.2.28) fig|6666666.60966.peg.934 CDS 865800
863752 -3 - 2049 DNA ligase (EC 6.5.1.2) DNA Repair Base D23_1c0939
Neut_0946 Excision fig|6666666.60966.peg.935 CDS 865959 866654 3 +
696 hypothetical protein -none- D23_1c0940 Neut_0947
fig|6666666.60966.peg.936 CDS 867392 867021 -2 - 372 Flagellar
biosynthesis Flagellum D23_1c0941 Neut_0948 protein FliT
fig|6666666.60966.peg.937 CDS 867859 867389 -1 - 471 Flagellar
biosynthesis Flagellum D23_1c0942 Neut_0949 protein FliS
fig|6666666.60966.peg.938 CDS 869359 867917 -1 - 1443 Flagellar
hook- Flagellum D23_1c0943 Neut_0950 associated protein FliD
fig|6666666.60966.peg.939 CDS 870186 869716 -3 - 471 hypothetical
protein -none- D23_1c0944 Neut_0951 fig|6666666.60966.peg.940 CDS
870616 870891 1 + 276 hypothetical protein -none- D23_1c0945
Neut_0952 fig|6666666.60966.peg.941 CDS 871905 870955 -3 - 951
Glutathione synthetase Glutathione: D23_1c0946 Neut_0953 (EC
6.3.2.3) Biosynthesis and gamma-glutamyl cycle; <br>Heat
shock dnaK gene cluster extended
fig|6666666.60966.peg.942 CDS 873212 871902 -2 - 1311
Glutamate--cysteine Glutathione: D23_1c0947 Neut_0954 ligase (EC
6.3.2.2), Biosynthesis and divergent, of Alpha- and gamma-glutamyl
cycle Beta-proteobacteria type fig|6666666.60966.peg.944 CDS 873411
873722 3 + 312 LSU ribosomal protein CBSS-176279.3.peg.868
D23_1c0949 Neut_0955 L21p fig|6666666.60966.peg.945 CDS 873734
873991 2 + 258 LSU ribosomal protein CBSS-176279.3.peg.868
D23_1c0950 Neut_0956 L27p fig|6666666.60966.peg.946 CDS 873991
874104 1 + 114 hypothetical protein -none- D23_1c0951 NA
fig|6666666.60966.peg.947 CDS 874121 875152 2 + 1032 GTP-binding
protein CBSS-176279.3.peg.868; D23_1c0952 Neut_0957 Obg
<br>Universal GTPases fig|6666666.60966.peg.948 CDS 875158
876279 1 + 1122 Glutamate 5-kinase (EC Proline Synthesis;
D23_1c0953 Neut_0958 2.7.2.11)/RNA-binding <br>Proline
Synthesis C-terminal domain PUA fig|6666666.60966.peg.949 CDS
876330 877331 3 + 1002 InterPro IPR000379 -none- D23_1c0954
Neut_0959 COGs COG0429 fig|6666666.60966.peg.950 CDS 877428 878744
3 + 1317 Phosphate regulon High affinity phosphate D23_1c0955
Neut_0960 sensor protein PhoR transporter and control (SphS) (EC
2.7.13.3) of PHO regulon; <br>PhoR-PhoB two- component
regulatory system; <br>Phosphate metabolism
fig|6666666.60966.peg.951 CDS 879101 879343 2 + 243 RNA-binding
protein Hfl operon; D23_1c0957 Neut_0961 Hfq
<br>Polyadenylation bacterial; <br>Possible RNA
degradation cluster fig|6666666.60966.peg.952 CDS 879345 880478 3 +
1134 GTP-binding protein Hfl operon; <br>Possible D23_1c0958
Neut_0962 HflX RNA degradation cluster; <br>Universal GTPases
fig|6666666.60966.peg.953 CDS 880535 881725 2 + 1191 HflK protein
Hfl operon; <br>Scaffold D23_1c0959 Neut_0963 proteins for
[4Fe--4S] cluster assembly (MRP family) fig|6666666.60966.peg.954
CDS 881725 882603 1 + 879 HflC protein Hfl operon;
<br>Scaffold D23_1c0960 Neut_0964 proteins for [4Fe--4S]
cluster assembly (MRP family) fig|6666666.60966.peg.955 CDS 882732
882917 3 + 186 Putative inner Hfl operon D23_1c0961 Neut_0965
membrane protein YjeT (clustered with HflC)
fig|6666666.60966.peg.956 CDS 882992 884164 2 + 1173 ATP Histidine
Biosynthesis D23_1c0962 Neut_0966 phosphoribosyltransferase
regulatory subunit (EC 2.4.2.17) fig|6666666.60966.peg.957 CDS
884298 885596 3 + 1299 Adenylosuccinate Purine conversions
D23_1c0963 Neut_0967 synthetase (EC 6.3.4.4)
fig|6666666.60966.peg.958 CDS 885982 885665 -1 - 318 FIG00858510:
-none- D23_1c0964 Neut_0968 hypothetical protein
fig|6666666.60966.peg.959 CDS 886361 886164 -2 - 198 FIG00859475:
-none- D23_1c0966 Neut_0969 hypothetical protein
fig|6666666.60966.peg.961 CDS 889010 886635 -2 - 2376 ATP-dependent
Proteasome bacterial; D23_1c0967 Neut_0970 protease La (EC
<br>Proteolysis in 3.4.21.53) Type I bacteria, ATP-dependent
fig|6666666.60966.peg.962 CDS 889609 889160 -1 - 450 CBS domain
protein -none- D23_1c0968 Neut_0971 fig|6666666.60966.peg.963 CDS
890160 889657 -3 - 504 hypothetical protein -none- D23_1c0969
Neut_0972 fig|6666666.60966.peg.964 CDS 890193 890345 3 + 153
hypothetical protein -none- D23_1c0970 NA fig|6666666.60966.peg.965
CDS 890326 890442 1 + 117 hypothetical protein -none- D23_1c0971 NA
fig|6666666.60966.peg.966 CDS 890503 891663 1 + 1161
ABC-transporter -none- D23_1c0972 Neut_0973 permease protein
fig|6666666.60966.peg.967 CDS 891663 892352 3 + 690 ABC
transporter, ATP- -none- D23_1c0973 Neut_0974 binding protein
fig|6666666.60966.peg.968 CDS 892533 893492 3 + 960 Membrane
protein -none- D23_1c0974 Neut_0975 fig|6666666.60966.peg.969 CDS
895517 893706 -2 - 1812 Sodium/hydrogen -none- D23_1c0976 Neut_0976
exchanger family protein fig|6666666.60966.peg.970 CDS 895888
896574 1 + 687 FIG00859851: -none- D23_1c0978 Neut_0977
hypothetical protein fig|6666666.60966.peg.971 CDS 897991 897029 -1
- 963 Mobile element protein -none- D23_1c0979 Neut_0978
fig|6666666.60966.peg.972 CDS 899539 898112 -1 - 1428 Pyruvate
kinase (EC Glycerate metabolism; D23_1c0980 Neut_0979 2.7.1.40)
<br>Glycolysis and Gluconeogenesis; <br>Pyruvate
metabolism I: anaplerotic reactions, PEP fig|6666666.60966.peg.973
CDS 899838 899563 -3 - 276 hypothetical protein -none- D23_1c0981
Neut_0980 fig|6666666.60966.peg.974 CDS 900234 900398 3 + 165
hypothetical protein -none- D23_1c0982 NA fig|6666666.60966.peg.975
CDS 903871 900686 -1 - 3186 TonB-dependent Ton and Tol transport
D23_1c0983 Neut_1076 receptor systems fig|6666666.60966.peg.976 CDS
904856 903873 -2 - 984 hypothetical protein -none- D23_1c0984
Neut_1077 fig|6666666.60966.peg.977 CDS 906168 904861 -3 - 1308
putative helicase -none- D23_1c0985 Neut_1078
fig|6666666.60966.peg.978 CDS 908497 906392 -1 - 2106 sucrose
synthase -none- D23_1c0988 Neut_1079 fig|6666666.60966.peg.979 CDS
910925 908787 -2 - 2139 Sucrose phosphate -none- D23_1c0989
Neut_1080 synthase fig|6666666.60966.peg.980 CDS 911865 910936 -3 -
930 Fructokinase (EC -none- D23_1c0990 Neut_1081 2.7.1.4)
fig|6666666.60966.peg.981 CDS 914147 912060 -2 - 2088 Excinuclease
ABC DNA repair, UvrABC D23_1c0991 Neut_1082 subunit B system
fig|6666666.60966.peg.982 CDS 914226 915419 3 + 1194 Aspartate
CBSS-216591.1.peg.168; D23_1c0992 Neut_1083 aminotransferase (EC
<br>Glutamine, 2.6.1.1) Glutamate, Aspartate and Asparagine
Biosynthesis; <br>Threonine and Homoserine Biosynthesis
fig|6666666.60966.peg.983 CDS 915551 915688 2 + 138 hypothetical
protein -none- D23_1c0993 NA fig|6666666.60966.peg.984 CDS 915891
916277 3 + 387 Mobile element protein -none- D23_1c0994 Neut_0884
fig|6666666.60966.peg.985 CDS 916240 916695 1 + 456 Mobile element
protein -none- D23_1c0995 Neut_2502 fig|6666666.60966.peg.986 CDS
916764 917726 3 + 963 Mobile element protein -none- D23_1c0996
Neut_1862 fig|6666666.60966.peg.987 CDS 918535 918419 -1 - 117
hypothetical protein -none- D23_1c0997 NA fig|6666666.60966.peg.988
CDS 919358 918504 -2 - 855 DNA-directed RNA RNA polymerase
D23_1c0998 NA polymerase alpha bacterial subunit (EC 2.7.7.6)
fig|6666666.60966.peg.989 CDS 919525 919409 -1 - 117 hypothetical
protein -none- D23_1c0999 Neut_1085 fig|6666666.60966.peg.990 CDS
919587 919787 3 + 201 Glutathione synthetase Glutathione:
D23_1c0999 Neut_1085 (EC 6.3.2.3) Biosynthesis and gamma-glutamyl
cycle; <br>Heat shock dnaK gene cluster extended
fig|6666666.60966.peg.991 CDS 919919 920287 2 + 369 FIG00858546:
-none- D23_1c1000 Neut_1086 hypothetical protein
fig|6666666.60966.peg.992 CDS 920496 921119 3 + 624 bacteriocin
resistance -none- D23_1c1001 Neut_1087 protein, putative
fig|6666666.60966.peg.993 CDS 921168 921644 3 + 477 FIG00859915:
-none- D23_1c1002 Neut_1088 hypothetical protein
fig|6666666.60966.peg.994 CDS 921659 923050 2 + 1392 FIG00858837:
-none- D23_1c1003 Neut_1089 hypothetical protein
fig|6666666.60966.peg.995 CDS 923533 923105 -1 - 429 Zn-dependent
-none- D23_1c1004 Neut_1090 hydrolases, including glyoxylases
fig|6666666.60966.peg.996 CDS 923845 924936 1 + 1092
Diaminohydroxyphosphoribosylaminopyrimidine Riboflavin, FMN and FAD
D23_1c1005 Neut_1091 deaminase (EC metabolism; 3.5.4.26)/5-amino-6-
<br>Riboflavin, FMN and (5- FAD metabolism;
phosphoribosylamino)uracil <br>Riboflavin, FMN and reductase
(EC FAD metabolism in 1.1.1.193) plants; <br>Riboflavin, FMN
and FAD metabolism in plants; <br>Riboflavin synthesis
cluster; <br>Riboflavin synthesis cluster
fig|6666666.60966.peg.997 CDS 925042 926262 1 + 1221 Glycosyl
transferase, -none- D23_1c1006 Neut_1092 group 1
fig|6666666.60966.peg.998 CDS 926363 927685 2 + 1323 UDP-glucose
-none- D23_1c1007 Neut_1093 dehydrogenase (EC 1.1.1.22)
fig|6666666.60966.peg.999 CDS 928127 928318 2 + 192 hypothetical
protein -none- D23_1c1009 Neut_1095 fig|6666666.60966.peg.1000 CDS
928500 928315 -3 - 186 hypothetical protein -none- D23_1c1010 NA
fig|6666666.60966.peg.1002 CDS 929085 930362 3 + 1278 InterPro
IPR001296 -none- D23_1c1011 Neut_1096 COGs COG0438
fig|6666666.60966.peg.1003 CDS 930467 931729 2 + 1263 Coenzyme F390
-none- D23_1c1012 Neut_1097 synthetase fig|6666666.60966.peg.1004
CDS 932351 931731 -2 - 621 exopolysaccharide -none- D23_1c1013
Neut_1098 synthesis protein ExoD- related protein
fig|6666666.60966.peg.1005 CDS 932631 933110 3 + 480 FIG00859304:
-none- D23_1c1014 Neut_1099 hypothetical protein
fig|6666666.60966.peg.1006 CDS 933200 934357 2 + 1158 FIG010505:
-none- D23_1c1015 Neut_1100 hypothetical protein
fig|6666666.60966.peg.1007 CDS 934409 935224 2 + 816 FIG00858774:
-none- D23_1c1016 Neut_1101 hypothetical protein
fig|6666666.60966.peg.1008 CDS 935243 936316 2 + 1074 Probable
-none- D23_1c1017 Neut_1102 transmembrane protein
fig|6666666.60966.peg.1009 CDS 936361 937383 1 + 1023 FIG000906:
Predicted -none- D23_1c1018 Neut_1103 Permease
fig|6666666.60966.peg.1010 CDS 937391 938608 2 + 1218 CDP-alcohol
-none- D23_1c1019 Neut_1104 phosphatidyltransferase
fig|6666666.60966.peg.1011 CDS 938637 939593 3 + 957 FIG00480695:
-none- D23_1c1020 Neut_1105 hypothetical protein
fig|6666666.60966.peg.1012 CDS 939607 940575 1 + 969 FIG00859274:
-none- D23_1c1021 Neut_1106 hypothetical protein
fig|6666666.60966.peg.1013 CDS 940636 941283 1 + 648 FIG00859276:
-none- D23_1c1022 Neut_1107 hypothetical protein
fig|6666666.60966.peg.1014 CDS 941749 941294 -1 - 456
Zn-ribbon-containing, DNA replication cluster 1 D23_1c1023
Neut_1108 possibly RNA-binding protein and truncated derivatives
fig|6666666.60966.peg.1016 CDS 942037 942186 1 + 150 hypothetical
protein -none- D23_1c1024 NA fig|6666666.60966.peg.1017 CDS 942242
944971 2 + 2730 Protein export -none- D23_1c1025 Neut_1109
cytoplasm protein SecA ATPase RNA helicase (TC 3.A.5.1.1)
fig|6666666.60966.peg.1018 CDS 945151 945756 1 + 606
Ubiquinol-cytochrome C Ubiquinone D23_1c1026 Neut_1110
reductase iron-sulfur Menaquinone- subunit (EC 1.10.2.2) cytochrome
c reductase complexes fig|6666666.60966.peg.1019 CDS 945758 947005
2 + 1248 Ubiquinol--cytochrome Ubiquinone D23_1c1027 Neut_1111 c
reductase, Menaquinone- cytochrome B subunit cytochrome c reductase
(EC 1.10.2.2) complexes fig|6666666.60966.peg.1020 CDS 947002
947706 1 + 705 ubiquinol cytochrome C Ubiquinone D23_1c1028
Neut_1112 oxidoreductase, Menaquinone- cytochrome C1 subunit
cytochrome c reductase complexes fig|6666666.60966.peg.1021 CDS
947758 948357 1 + 600 Stringent starvation Carbon Starvation
D23_1c1029 Neut_1113 protein A fig|6666666.60966.peg.1023 CDS
949015 949215 1 + 201 hypothetical protein -none- D23_1c1031
Neut_2449 fig|6666666.60966.peg.1024 CDS 949203 949682 3 + 480
Mobile element protein -none- D23_1c1032 Neut_2417
fig|6666666.60966.peg.1025 CDS 950361 950651 3 + 291 Mobile element
protein -none- D23_1c1034 Neut_2190 fig|6666666.60966.peg.1026 CDS
951943 950696 -1 - 1248 Mobile element protein -none- D23_1c1035
Neut_0357 fig|6666666.60966.peg.1027 CDS 952378 952208 -1 - 171
hypothetical protein -none- D23_1c1036 NA
fig|6666666.60966.peg.1028 CDS 953114 952689 -2 - 426 C4-type zinc
finger Zinc regulated enzymes D23_1c1037 Neut_1117 protein,
DksA/TraR family fig|6666666.60966.peg.1029 CDS 955194 953479 -3 -
1716 Adenylate cyclase (EC cAMP signaling in D23_1c1038 Neut_1118
4.6.1.1) bacteria fig|6666666.60966.peg.1030 CDS 956008 955157 -1 -
852 HD domain -none- D23_1c1039 Neut_1119
fig|6666666.60966.peg.1032 CDS 956563 957111 1 + 549 InterPro
IPR000345 -none- D23_1c1042 Neut_1126 fig|6666666.60966.peg.1033
CDS 958663 957200 -1 - 1464 3-polyprenyl-4- Ubiquinone D23_1c1043
Neut_1127 hydroxybenzoate Biosynthesis; carboxy-lyase (EC
<br>Ubiquinone 4.1.1.--) Biosynthesis-gjo
fig|6666666.60966.peg.1034 CDS 959616 958756 -3 - 861
4-hydroxybenzoate Ubiquinone D23_1c1045 Neut_1128
polyprenyltransferase Biosynthesis; (EC 2.5.1.39)
<br>Ubiquinone Biosynthesis-gjo fig|6666666.60966.peg.1035
CDS 960159 959695 -3 - 465 Chorismate--pyruvate Ubiquinone
D23_1c1046 Neut_1129 lyase (EC 4.1.3.40) Biosynthesis;
<br>Ubiquinone Biosynthesis-gjo fig|6666666.60966.peg.1036
CDS 960706 960299 -1 - 408 twitching motility -none- D23_1c1047
Neut_1130 protein PilG fig|6666666.60966.peg.1037 CDS 962283 960874
-3 - 1410 Potassium uptake Hyperosmotic potassium D23_1c1048
Neut_1131 protein TrkH uptake; <br>Potassium homeostasis;
<br>Potassium homeostasis fig|6666666.60966.peg.1038 CDS
963803 962355 -2 - 1449 Trk system potassium Bacterial RNA-
D23_1c1049 Neut_1132 uptake protein TrkA metabolizing Zn- dependent
hydrolases; <br>Hyperosmotic potassium uptake;
<br>Possible RNA degradation cluster; <br>Potassium
homeostasis; <br>Potassium homeostasis
fig|6666666.60966.peg.1039 CDS 965344 964070 -1 - 1275 FIG00858490:
-none- D23_1c1050 Neut_1133 hypothetical protein
fig|6666666.60966.peg.1040 CDS 965355 965495 3 + 141 hypothetical
protein -none- D23_1c1051 NA fig|6666666.60966.peg.1041 CDS 965968
965477 -1 - 492 Starvation lipoprotein Carbon Starvation D23_1c1052
Neut_1134 Slp paralog fig|6666666.60966.peg.1042 CDS 966371 967021
2 + 651 Septum site- Bacterial Cell Division; D23_1c1054 Neut_1135
determining protein <br>Bacterial MinC Cytoskeleton;
<br>Bacterial cell division cluster; <br>Septum site-
determining cluster Min fig|6666666.60966.peg.1043 CDS 967047
967856 3 + 810 Septum site- Bacterial Cell Division; D23_1c1055
Neut_1136 determining protein <br>Bacterial MinD
Cytoskeleton; <br>Bacterial cell division cluster;
<br>Septum site- determining cluster Min
fig|6666666.60966.peg.1044 CDS 967856 968152 2 + 297 Cell division
topological Bacterial Cell Division; D23_1c1056 Neut_1137
specificity factor MinE <br>Bacterial Cytoskeleton;
<br>Bacterial cell division cluster; <br>Septum site-
determining cluster Min fig|6666666.60966.peg.1045 CDS 968284
968895 1 + 612 Outer membrane A Gammaproteobacteria D23_1c1057
Neut_1138 lipoprotein LolB Cluster Relating to Translation;
<br>Lipopolysaccharide assembly; <br>Lipoprotein
sorting system fig|6666666.60966.peg.1046 CDS 968920 969756 1 + 837
4-diphosphocytidyl-2-C- A Gammaproteobacteria D23_1c1058 Neut_1139
methyl-D-erythritol Cluster Relating to kinase (EC 2.7.1.148)
Translation; <br>Isoprenoid Biosynthesis;
<br>Nonmevalonate Branch of Isoprenoid Biosynthesis
fig|6666666.60966.peg.1047 CDS 969932 970882 2 + 951
Ribose-phosphate A Gammaproteobacteria D23_1c1060 Neut_1140
pyrophosphokinase (EC Cluster Relating to 2.7.6.1) Translation;
<br>De Novo Purine Biosynthesis; <br>Pentose phosphate
pathway; <br>Transcription repair cluster
fig|6666666.60966.peg.1048 CDS 970936 971544 1 + 609 LSU ribosomal
protein Transcription repair D23_1c1061 Neut_1141 L25p cluster
fig|6666666.60966.peg.1049 CDS 971667 972236 3 + 570 Peptidyl-tRNA
Sporulation-associated D23_1c1062 Neut_1142 hydrolase (EC 3.1.1.29)
proteins with broader functions; <br>Transcription repair
cluster; <br>Translation termination factors bacterial
fig|6666666.60966.peg.1050 CDS 972291 973382 3 + 1092 GTP-binding
and nucleic Universal GTPases D23_1c1063 Neut_1143 acid-binding
protein YchF fig|6666666.60966.peg.1051 CDS 973589 973461 -2 - 129
hypothetical protein -none- D23_1c1064 NA
fig|6666666.60966.peg.1052 CDS 973891 975303 1 + 1413
3-isopropylmalate Branched-Chain Amino D23_1c1066 Neut_1144
dehydratase large Acid Biosynthesis; subunit (EC 4.2.1.33)
<br>Leucine Biosynthesis fig|6666666.60966.peg.1053 CDS
975336 975464 3 + 129 FIG00858504: -none- D23_1c1067 Neut_1145
hypothetical protein fig|6666666.60966.peg.1054 CDS 975470 976108 2
+ 639 3-isopropylmalate Branched-Chain Amino D23_1c1068 Neut_1146
dehydratase small Acid Biosynthesis; subunit (EC 4.2.1.33)
<br>Leucine Biosynthesis fig|6666666.60966.peg.1055 CDS
976133 977203 2 + 1071 3-isopropylmalate Branched-Chain Amino
D23_1c1069 Neut_1147 dehydrogenase (EC Acid Biosynthesis; 1.1.1.85)
<br>Leucine Biosynthesis fig|6666666.60966.peg.1056 CDS
977333 978457 2 + 1125 Aspartate- Lysine Biosynthesis DAP
D23_1c1070 Neut_1148 semialdehyde Pathway, GJO scratch;
dehydrogenase (EC <br>Threonine and 1.2.1.11) Homoserine
Biosynthesis fig|6666666.60966.peg.1057 CDS 978574 980970 1 + 2397
hypothetical protein -none- D23_1c1071 Neut_1149
fig|6666666.60966.peg.1058 CDS 981084 981917 3 + 834 tRNA
pseudouridine Colicin V and Bacteriocin D23_1c1072 Neut_1150
synthase A (EC 4.2.1.70) Production Cluster; <br>RNA
pseudouridine syntheses; <br>tRNA modification Bacteria;
<br>tRNA processing fig|6666666.60966.peg.1059 CDS 981929
982555 2 + 627 Phosphoribosylanthranilate Auxin biosynthesis;
D23_1c1073 Neut_1151 isomerase (EC <br>Chorismate: 5.3.1.24)
Intermediate for synthesis of Tryptophan, PAPA antibiotics, PABA,
3-hydroxyanthranilate and more.; <br>Tryptophan synthesis
fig|6666666.60966.peg.1060 CDS 982542 983741 3 + 1200 Tryptophan
synthase Auxin biosynthesis; D23_1c1074 Neut_1152 beta chain (EC
4.2.1.20) <br>Chorismate: Intermediate for synthesis of
Tryptophan, PAPA antibiotics, PABA, 3-hydroxyanthranilate and
more.; <br>Tryptophan synthesis fig|6666666.60966.peg.1061
CDS 983794 984618 1 + 825 Tryptophan synthase Auxin biosynthesis;
D23_1c1075 Neut_1153 alpha chain (EC <br>Chorismate:
4.2.1.20) Intermediate for synthesis of Tryptophan, PAPA
antibiotics, PABA, 3-hydroxyanthranilate and more.;
<br>Tryptophan synthesis fig|6666666.60966.peg.1062 CDS
984623 985513 2 + 891 Acetyl-coenzyme A Colicin V and Bacteriocin
D23_1c1076 Neut_1154 carboxyl transferase Production Cluster; beta
chain (EC 6.4.1.2) <br>Fatty Acid Biosynthesis FASII
fig|6666666.60966.peg.1063 CDS 985642 986925 1 + 1284 Dihydrofolate
synthase Colicin V and Bacteriocin D23_1c1077 Neut_1155 (EC
6.3.2.12)/ Production Cluster; Folylpolyglutamate <br>Colicin
V and synthase (EC 6.3.2.17) Bacteriocin Production Cluster;
<br>Folate Biosynthesis; <br>Folate Biosynthesis
fig|6666666.60966.peg.1064 CDS 986945 987616 2 + 672 DedD protein
Colicin V and Bacteriocin D23_1c1078 Neut_1156 Production Cluster
fig|6666666.60966.peg.1065 CDS 987613 988107 1 + 495 Colicin V
production Colicin V and Bacteriocin D23_1c1079 Neut_1157 protein
Production Cluster fig|6666666.60966.peg.1066 CDS 988214 989731 2 +
1518 Amidophosphoribosyltransferase Colicin V and Bacteriocin
D23_1c1080 Neut_1158 (EC 2.4.2.14) Production Cluster; <br>De
Novo Purine Biosynthesis fig|6666666.60966.peg.1067 CDS 989748
990923 3 + 1176 O-acetylhomoserine Methionine D23_1c1081 Neut_1159
sulfhydrylase (EC Biosynthesis; 2.5.1.49)/O- <br>Methionine
succinylhomoserine Biosynthesis sulfhydrylase (EC 2.5.1.48)
fig|6666666.60966.peg.1068 CDS 991043 992554 2 + 1512 Threonine
dehydratase Branched-Chain Amino D23_1c1082 Neut_1160 biosynthetic
(EC Acid Biosynthesis 4.3.1.19) fig|6666666.60966.peg.1069 CDS
992670 992536 -3 - 135 hypothetical protein -none- D23_1c1083 NA
fig|6666666.60966.peg.1070 CDS 993016 994950 1 + 1935 twitching
motility
-none- D23_1c1084 Neut_1161 protein PilJ fig|6666666.60966.peg.1071
CDS 995179 995054 -1 - 126 hypothetical protein -none- D23_1c1085
Neut_1162 fig|6666666.60966.peg.1072 CDS 995174 1000177 2 + 5004
Signal transduction Flagellar motility D23_1c1085 Neut_1162
histidine kinase CheA (EC 2.7.3.--) fig|6666666.60966.peg.1073 CDS
1000248 1002095 3 + 1848 ParB-like nuclease -none- D23_1c1086
Neut_1163 domain fig|6666666.60966.peg.1074 CDS 1003717 1002203 -1
- 1515 Ubiquinone Ubiquinone D23_1c1087 Neut_1164 biosynthesis
Biosynthesis; monooxygenase UbiB <br>Ubiquinone
Biosynthesis-gjo fig|6666666.60966.peg.1075 CDS 1004439 1003807 -3
- 633 Protein YigP (COG3165) Ubiquinone D23_1c1088 Neut_1165
clustered with Biosynthesis; ubiquinone biosynthetic
<br>Ubiquinone genes Biosynthesis-gjo
fig|6666666.60966.peg.1076 CDS 1004959 1004528 -1 - 432
FIG00858586: -none- D23_1c1089 Neut_1166 hypothetical protein
fig|6666666.60966.peg.1077 CDS 1005165 1004962 -3 - 204
hypothetical protein -none- D23_1c1090 NA
fig|6666666.60966.peg.1078 CDS 1005185 1007323 2 + 2139 Signal
transduction Flagellar motility D23_1c1091 Neut_1167 histidine
kinase CheA (EC 2.7.3.--) fig|6666666.60966.peg.1079 CDS 1007395
1007916 1 + 522 Positive regulator of -none- D23_1c1092 Neut_1168
CheA protein activity (CheW) fig|6666666.60966.peg.1080 CDS 1008003
1010258 3 + 2256 Methyl-accepting -none- D23_1c1093 Neut_1169
chemotaxis protein I (serine chemoreceptor protein)
fig|6666666.60966.peg.1082 CDS 1010399 1012744 2 + 2346
Methyl-accepting -none- D23_1c1094 Neut_1170 chemotaxis protein I
(serine chemoreceptor protein) fig|6666666.60966.peg.1083 CDS
1012932 1013807 3 + 876 Chemotaxis protein -none- D23_1c1095
Neut_1171 methyltransferase CheR (EC 2.1.1.80)
fig|6666666.60966.peg.1084 CDS 1013887 1014471 1 + 585 Chemotaxis
protein -none- D23_1c1096 Neut_1172 CheD fig|6666666.60966.peg.1085
CDS 1014502 1015569 1 + 1068 Chemotaxis response -none- D23_1c1097
Neut_1173 regulator protein- glutamate methylesterase CheB (EC
3.1.1.61) fig|6666666.60966.peg.1087 CDS 1017858 1016338 -3 - 1521
Ferredoxin reductase Anaerobic respiratory D23_1c1099 Neut_1175
reductases fig|6666666.60966.peg.1088 CDS 1018141 1019145 1 + 1005
Fructose-1,6- Calvin-Benson cycle; D23_1c1100 Neut_1176
bisphosphatase, type I <br>Glycolysis and (EC 3.1.3.11)
Gluconeogenesis fig|6666666.60966.peg.1089 CDS 1020142 1019183 -1 -
960 Glutathione S- Glutathione: Non-redox D23_1c1101 Neut_1177
transferase, omega (EC reactions 2.5.1.18)
fig|6666666.60966.peg.1090 CDS 1020604 1020146 -1 - 459 Membrane
protein, -none- D23_1c1102 Neut_1178 distant similarity to
thiosulphate:quinone oxidoreductase DoxD fig|6666666.60966.peg.1091
CDS 1020710 1020862 2 + 153 hypothetical protein -none- D23_1c1103
NA fig|6666666.60966.peg.1092 CDS 1022088 1021138 -3 - 951 COGs
COG0726 -none- D23_1c1104 Neut_1179 fig|6666666.60966.peg.1093 CDS
1022664 1022212 -3 - 453 Phosphohistidine -none- D23_1c1105
Neut_1180 phosphatase SixA fig|6666666.60966.peg.1094 CDS 1023442
1022753 -1 - 690 COGs COG1814 -none- D23_1c1106 Neut_1181
fig|6666666.60966.peg.1095 CDS 1024149 1023445 -3 - 705 probable
-none- D23_1c1107 Neut_1182 carboxylesterase
fig|6666666.60966.peg.1096 CDS 1024228 1025334 1 + 1107 InterPro
IPR002931 -none- D23_1c1108 Neut_1183 COGs COG1305
fig|6666666.60966.peg.1097 CDS 1027262 1025541 -2 - 1722 Sulfite
reductase Cysteine Biosynthesis; D23_1c1109 Neut_1184 [NADPH]
hemoprotein <br>Inorganic Sulfur beta-component (EC
Assimilation 1.8.1.2) fig|6666666.60966.peg.1098 CDS 1029106
1027271 -1 - 1836 Sulfite reductase Cysteine Biosynthesis;
D23_1c1110 Neut_1185 [NADPH] flavoprotein <br>Inorganic
Sulfur alpha-component (EC Assimilation 1.8.1.2)
fig|6666666.60966.peg.1100 CDS 1030580 1029651 -2 - 930 Cys regulon
Cysteine Biosynthesis; D23_1c1111 Neut_1186 transcriptional
activator <br>LysR-family proteins CysB in Escherichia coli
fig|6666666.60966.peg.1101 CDS 1030815 1031513 3 + 699
Phosphoadenylyl- Cysteine Biosynthesis; D23_1c1112 Neut_1187
sulfate reductase <br>Inorganic Sulfur [thioredoxin] (EC
Assimilation; 1.8.4.8)/Adenylyl- <br>Inorganic Sulfur sulfate
reductase Assimilation [thioredoxin] (EC 1.8.4.10)
fig|6666666.60966.peg.1102 CDS 1031599 1032447 1 + 849 Sulfate
Cysteine Biosynthesis; D23_1c1113 Neut_1188 adenylyltransferase
<br>Inorganic Sulfur subunit 2 (EC 2.7.7.4) Assimilation
fig|6666666.60966.peg.1103 CDS 1032508 1033791 1 + 1284 Sulfate
Cysteine Biosynthesis; D23_1c1114 Neut_1189 adenylyltransferase
<br>Inorganic Sulfur subunit 1 (EC 2.7.7.4) Assimilation
fig|6666666.60966.peg.1105 CDS 1033967 1037446 2 + 3480 Glutamate
synthase Ammonia assimilation; D23_1c1115 Neut_1190 [NADPH] small
chain <br>Glutamine, (EC 1.4.1.13) Glutamate, Aspartate and
Asparagine Biosynthesis fig|6666666.60966.peg.1106 CDS 1037596
1038723 1 + 1128 NAD(P) Phosphate metabolism D23_1c1116 Neut_1191
transhydrogenase alpha subunit (EC 1.6.1.2)
fig|6666666.60966.peg.1107 CDS 1038778 1039086 1 + 309 NAD(P)
Phosphate metabolism D23_1c1117 Neut_1192 transhydrogenase alpha
subunit (EC 1.6.1.2) fig|6666666.60966.peg.1108 CDS 1039087 1040466
1 + 1380 NAD(P) Phosphate metabolism D23_1c1118 Neut_1193
transhydrogenase subunit beta (EC 1.6.1.2)
fig|6666666.60966.peg.1109 CDS 1041147 1040488 -3 - 660
FIG00858826: -none- D23_1c1119 Neut_1194 hypothetical protein
fig|6666666.60966.peg.1110 CDS 1042046 1041582 -2 - 465
Bacterioferritin -none- D23_1c1120 Neut_1195
fig|6666666.60966.peg.1112 CDS 1043119 1043253 1 + 135 hypothetical
protein -none- D23_1c1121 NA fig|6666666.60966.peg.1113 CDS 1043368
1043511 1 + 144 hypothetical protein -none- D23_1c1122 NA
fig|6666666.60966.peg.1115 CDS 1043900 1043736 -2 - 165
hypothetical protein -none- D23_1c1123 NA
fig|6666666.60966.peg.1116 CDS 1043900 1044847 2 + 948 2,3- -none-
D23_1c1124 Neut_1198 bisphosphoglycerate- independent
phosphoglycerate mutase fig|6666666.60966.peg.1117 CDS 1044958
1045530 1 + 573 InterPro -none- D23_1c1125 Neut_1199
IPR000014:IPR001633 COGs COG2200 fig|6666666.60966.peg.1118 CDS
1045566 1045859 3 + 294 Mobile element protein -none- D23_1c1126
Neut_1719 fig|6666666.60966.peg.1119 CDS 1045958 1046836 2 + 879
Mobile element protein -none- D23_1c1127 Neut_1720
fig|6666666.60966.peg.1120 CDS 1046891 1047784 2 + 894 InterPro
-none- D23_1c1128 Neut_1199 IPR000014:IPR001633 COGs COG2200
fig|6666666.60966.peg.1121 CDS 1048688 1047801 -2 - 888
Phosphoribosylaminoimidazole- De Novo Purine D23_1c1129 Neut_1200
succinocarboxamide Biosynthesis synthase (EC 6.3.2.6)
fig|6666666.60966.peg.1122 CDS 1049856 1048726 -3 - 1131
Phosphoribosylaminoimidazole De Novo Purine D23_1c1130 Neut_1201
carboxylase Biosynthesis ATPase subunit (EC 4.1.1.21)
fig|6666666.60966.peg.1123 CDS 1050317 1049847 -2 - 471
Phosphoribosylaminoimidazole De Novo Purine D23_1c1131 Neut_1202
carboxylase Biosynthesis catalytic subunit (EC 4.1.1.21)
fig|6666666.60966.peg.1124 CDS 1050521 1050955 2 + 435 Biopolymer
transport Ton and Tol transport D23_1c1133 Neut_1203 protein
ExbD/TolR systems fig|6666666.60966.peg.1125 CDS 1050942 1051664 3
+ 723 Superoxide dismutase Oxidative stress; D23_1c1134 Neut_1204
[Fe] (EC 1.15.1.1) <br>Protection from Reactive Oxygen
Species fig|6666666.60966.peg.1126 CDS 1051674 1052324 3 + 651 ATP
Histidine Biosynthesis; D23_1c1135 Neut_1205
phosphoribosyltransferase <br>Riboflavin synthesis (EC
2.4.2.17) cluster fig|6666666.60966.peg.1127 CDS 1052409 1053644 3
+ 1236 Histidinol Histidine Biosynthesis D23_1c1136 Neut_1206
dehydrogenase (EC 1.1.1.23) fig|6666666.60966.peg.1128 CDS 1053708
1054883 3 + 1176 2-octaprenyl-6- CBSS-87626.3.peg.3639; D23_1c1137
Neut_1207 methoxyphenol <br>Ubiquinone hydroxylase (EC
Biosynthesis; 1.14.13.--) <br>Ubiquinone Biosynthesis-gjo
fig|6666666.60966.peg.1129 CDS 1055047 1056060 1 + 1014 tRNA
dihydrouridine Possible RNA D23_1c1138 Neut_1208 synthase B (EC
1.--.--.--) degradation cluster; <br>tRNA modification
Bacteria fig|6666666.60966.peg.1130 CDS 1056057 1056299 3 + 243
DNA-binding protein Fis DNA structural proteins, D23_1c1139
Neut_1209 bacterial fig|6666666.60966.peg.1131 CDS 1056309 1057871
3 + 1563 IMP cyclohydrolase (EC 5-FCL-like protein; D23_1c1140
Neut_1210 3.5.4.10)/ <br>De Novo Purine
Phosphoribosylaminoimidazolecarboxamide Biosynthesis; <br>De
formyltransferase (EC Novo Purine 2.1.2.3) Biosynthesis
fig|6666666.60966.peg.1132 CDS 1057947 1059233 3 + 1287
Phosphoribosylamine- De Novo Purine D23_1c1141 Neut_1211 glycine
ligase (EC Biosynthesis 6.3.4.13) fig|6666666.60966.peg.1133 CDS
1059226 1060497 1 + 1272 FIG00858582: -none- D23_1c1142 Neut_1213
hypothetical protein fig|6666666.60966.peg.1134 CDS 1061025 1060582
-3 - 444 TPR repeat precursor -none- D23_1c1143 Neut_1214
fig|6666666.60966.peg.1135 CDS 1061496 1061041 -3 - 456 Mobile
element protein -none- D23_1c1144 Neut_2502
fig|6666666.60966.peg.1136 CDS 1061839 1061459 -1 - 381 Mobile
element protein -none- D23_1c1145 Neut_0884
fig|6666666.60966.peg.1137 CDS 1062885 1061836 -3 - 1050 TPR repeat
precursor -none- D23_1c1146 Neut_0701 fig|6666666.60966.peg.1138
CDS 1064906 1062960 -2 - 1947 DinG family ATP- DNA repair,
bacterial D23_1c1148 Neut_1215 dependent helicase DinG and
relatives YoaA fig|6666666.60966.peg.1139 CDS 1065051 1064932 -3 -
120 hypothetical protein -none- D23_1c1149 NA
fig|6666666.60966.peg.1140 CDS 1065126 1067303 3 + 2178 Outer
membrane EC49-61; <br>ECSIG4- D23_1c1150 Neut_1216 protein
Imp, required SIG7; for envelope biogenesis/
<br>Lipopolysaccharide Organic solvent assembly tolerance
protein precursor fig|6666666.60966.peg.1141 CDS 1067300 1068643 2
+ 1344 Survival protein SurA EC49-61; <br>ECSIG4- D23_1c1151
Neut_1217 precursor (Peptidyl- SIG7; prolyl cis-trans
<br>Lipopolysaccharide isomerase SurA) (EC assembly;
<br>Peptidyl- 5.2.1.8) prolyl cis-trans isomerase;
<br>Periplasmic Stress Response fig|6666666.60966.peg.1142
CDS 1068713 1069750 2 + 1038 4-hydroxythreonine-4- EC49-61;
<br>ECSIG4- D23_1c1152 Neut_1218 phosphate SIG7;
<br>Pyridoxin dehydrogenase (EC (Vitamin B6) 1.1.1.262)
Biosynthesis fig|6666666.60966.peg.1143 CDS 1069754 1070524 2 + 771
SSU rRNA EC49-61; <br>ECSIG4- D23_1c1153 Neut_1219
(adenine(1518)- SIG7; <br>RNA N(6)/adenine(1519)-
methylation; N(6))- <br>Ribosome dimethyltransferase (EC
biogenesis bacterial 2.1.1.182) ## SSU rRNA m6,m6-A1518-1519
fig|6666666.60966.peg.1144 CDS 1071020 1070517 -2 - 504
Methylated-DNA-- DNA repair, bacterial D23_1c1154 Neut_1220
protein-cysteine methyltransferase (EC 2.1.1.63)
fig|6666666.60966.peg.1145 CDS 1071346 1071080 -1 - 267 ADA
regulatory protein/ DNA repair, bacterial; D23_1c1155 Neut_1221
Methylated-DNA-- <br>DNA repair, protein-cysteine bacterial
methyltransferase (EC 2.1.1.63) fig|6666666.60966.peg.1146 CDS
1072448 1071324 -2 - 1125 ADA regulatory protein/ DNA repair,
bacterial; D23_1c1156 Neut_1221 Methylated-DNA-- <br>DNA
repair, protein-cysteine bacterial methyltransferase (EC 2.1.1.63)
fig|6666666.60966.peg.1149 CDS 1073291 1073809 2 + 519
Helix-turn-helix motif -none- D23_1c1157 Neut_1223
fig|6666666.60966.peg.1150 CDS 1075783 1074353 -1 - 1431 Siroheme
synthase/ Heme and Siroheme D23_1c1159 Neut_1002 Precorrin-2
oxidase (EC Biosynthesis; <br>Heme 1.3.1.76)/ and Siroheme
Sirohydrochlorin Biosynthesis; <br>Heme ferrochelatase (EC
and Siroheme 4.99.1.4)/ Biosynthesis Uroporphyrinogen-III
methyltransferase (EC 2.1.1.107) fig|6666666.60966.peg.1151 CDS
1076939 1075926 -2 - 1014 Phosphate ABC High affinity phosphate
D23_1c1160 Neut_1001 transporter, periplasmic transporter and
control phosphate-binding of PHO regulon; protein PstS (TC
<br>PhoR-PhoB two- 3.A.1.7.1) component regulatory system;
<br>Phosphate metabolism fig|6666666.60966.peg.1152 CDS
1078435 1077059 -1 - 1377 Phosphoglucosamine Sialic Acid
Metabolism; D23_1c1161 Neut_1000 mutase (EC 5.4.2.10)
<br>UDP-N- acetylmuramate from Fructose-6-phosphate
Biosynthesis fig|6666666.60966.peg.1153 CDS 1079505 1078603 -3 -
903 Dihydropteroate Folate Biosynthesis D23_1c1162 Neut_0999
synthase (EC 2.5.1.15) fig|6666666.60966.peg.1154 CDS 1081457
1079529 -2 - 1929 Cell division protein Bacterial Cell Division
D23_1c1163 Neut_0998 FtsH (EC 3.4.24.--) fig|6666666.60966.peg.1155
CDS 1082161 1081541 -1 - 621 Cell division protein FtsJ/ Bacterial
Cell Division; D23_1c1164 Neut_0997 Ribosomal RNA large
<br>RNA methylation subunit methyltransferase E (EC 2.1.1.--)
## LSU rRNA Um2552 fig|6666666.60966.peg.1156 CDS 1082195 1082575 2
+ 381 FIG004454: RNA -none- D23_1c1165 Neut_0996 binding protein
fig|6666666.60966.peg.1157 CDS 1082674 1083084 1 + 411 CBS domain
-none- D23_1c1166 Neut_0995 fig|6666666.60966.peg.1158 CDS 1083081
1083464 3 + 384 tRNA A cluster relating to D23_1c1167 Neut_0994
nucleotidyltransferase, Tryptophanyl-tRNA A-adding (EC 2.7.7.25)
synthetase; <br>Polyadenylation bacterial; <br>tRNA
nucleotidyltransferase fig|6666666.60966.peg.1159 CDS 1084218
1083646 -3 - 573 DNA-3-methyladenine DNA Repair Base D23_1c1168
Neut_0993 glycosylase II (EC Excision 3.2.2.21)
fig|6666666.60966.peg.1160 CDS 1084717 1084241 -1 - 477 Glutathione
peroxidase Glutathione: Redox cycle D23_1c1169 Neut_0992 (EC
1.11.1.9) fig|6666666.60966.peg.1161 CDS 1084748 1085341 2 + 594
Carbonic anhydrase, Zinc regulated enzymes D23_1c1170 Neut_0991
gamma class (EC 4.2.1.1) fig|6666666.60966.peg.1162 CDS 1085402
1086241 2 + 840 Putative NAD(P)- -none- D23_1c1171 Neut_0990
dependent oxidoreductase EC- YbbO fig|6666666.60966.peg.1163 CDS
1086401 1087885 2 + 1485 alpha amylase, catalytic -none- D23_1c1172
Neut_0989 region fig|6666666.60966.peg.1164 CDS 1090985 1087899 -2
- 3087 RND multidrug efflux Multidrug Resistance D23_1c1173
Neut_0988 transporter; Acriflavin Efflux Pumps resistance protein
fig|6666666.60966.peg.1165 CDS 1092079 1090982 -1 - 1098 Membrane
fusion Multidrug Resistance D23_1c1174 Neut_0987 protein of RND
family Efflux Pumps multidrug efflux pump
fig|6666666.60966.peg.1168 CDS 1092982 1092851 -1 - 132
hypothetical protein -none- D23_1c1175 NA
fig|6666666.60966.peg.1169 CDS 1094042 1093413 -2 - 630
Nicotinamidase family NAD and NADP cofactor D23_1c1176 NA protein
YcaC biosynthesis global fig|6666666.60966.peg.1170 CDS 1094408
1094223 -2 - 186 Mobile element protein -none- D23_1c1178 Neut_1984
fig|6666666.60966.peg.1171 CDS 1094750 1094514 -2 - 237 Mobile
element protein -none- D23_1c1179 Neut_1353
fig|6666666.60966.peg.1172 CDS 1095334 1094984 -1 - 351
hypothetical protein -none- D23_1c1180 NA
fig|6666666.60966.peg.1173 CDS 1095854 1095486 -2 - 369 Mobile
element protein -none- D23_1c1181 Neut_2502
fig|6666666.60966.peg.1175 CDS 1096049 1095933 -2 - 117 Mobile
element protein -none- D23_1c1182 Neut_0884
fig|6666666.60966.peg.1176 CDS 1096623 1096288 -3 - 336 putative
(AJ245540) -none- D23_1c1183 Neut_1054 NrfJ [Wolinella
succinogenes] fig|6666666.60966.peg.1177 CDS 1098408 1096669 -3 -
1740 FIG00859793: -none- D23_1c1184 Neut_1053 hypothetical protein
fig|6666666.60966.peg.1178 CDS 1098651 1100255 3 + 1605 Multicopper
oxidase Copper homeostasis D23_1c1185 Neut_1052
fig|6666666.60966.peg.1179 CDS 1101152 1100349 -2 - 804 Inositol-1-
-none- D23_1c1186 Neut_1051 monophosphatase (EC 3.1.3.25)
fig|6666666.60966.peg.1180 CDS 1101712 1101155 -1 - 558 Alkyl
hydroperoxide -none- D23_1c1187 Neut_1050 reductase and/or thiol-
specific antioxidant family (AhpC/TSA) protein
fig|6666666.60966.peg.1181 CDS 1101810 1102571 3 + 762 Ribosomal
RNA small Heat shock dnaK gene D23_1c1188 Neut_1049 subunit cluster
extended; methyltransferase E (EC <br>RNA methylation
2.1.1.--) fig|6666666.60966.peg.1182 CDS 1102595 1103929 2 + 1335
N-acetylglutamate Arginine Biosynthesis-- D23_1c1189 Neut_1048
synthase (EC 2.3.1.1) gjo; <br>Arginine Biosynthesis extended
fig|6666666.60966.peg.1183 CDS 1104924 1104208 -3 - 717 FIG002842:
-none- D23_1c1190 Neut_1046 hypothetical protein
fig|6666666.60966.peg.1184 CDS 1105647 1105036 -3 - 612
Dephospho-CoA kinase Coenzyme A D23_1c1191 Neut_1045 (EC 2.7.1.24)
Biosynthesis fig|6666666.60966.peg.1185 CDS 1106511 1105651 -3 -
861 Leader peptidase -none- D23_1c1192 Neut_1044 (Prepilin
peptidase) (EC 3.4.23.43)/N- methyltransferase (EC 2.1.1.--)
fig|6666666.60966.peg.1186 CDS 1107775 1106555 -1 - 1221 Type IV
fimbrial -none- D23_1c1193 Neut_1043 assembly protein PilC
fig|6666666.60966.peg.1187 CDS 1108692 1107835 -3 - 858 Nucleoside-
CBSS-296591.1.peg.2330 D23_1c1194 Neut_1042 diphosphate-sugar
epimerases fig|6666666.60966.peg.1189 CDS 1108961 1109818 2 + 858
2-polyprenylphenol -none- D23_1c1195 Neut_1041 hydroxylase and
related flavodoxin oxidoreductases/CDP- 6-deoxy-delta-3,4-
glucoseen reductase- like fig|6666666.60966.peg.1190 CDS 1111006
1109825 -1 - 1182 Homolog of E. coli -none- D23_1c1196 Neut_1040
HemY protein fig|6666666.60966.peg.1191 CDS 1112031 1111003 -3 -
1029 Uroporphyrinogen-III Heme and Siroheme D23_1c1197 Neut_1039
methyltransferase (EC Biosynthesis 2.1.1.107)
fig|6666666.60966.peg.1192 CDS 1112828 1112046 -2 - 783
Uroporphyrinogen-III Heme and Siroheme D23_1c1198 Neut_1038
synthase (EC 4.2.1.75) Biosynthesis fig|6666666.60966.peg.1193 CDS
1113852 1112848 -3 - 1005 Porphobilinogen Heme and Siroheme
D23_1c1199 Neut_1037 deaminase (EC 2.5.1.61) Biosynthesis
fig|6666666.60966.peg.1194 CDS 1113898 1116699 1 + 2802
Phosphoenolpyruvate Pyruvate metabolism I: D23_1c1200 Neut_1036
carboxylase (EC anaplerotic reactions, 4.1.1.31) PEP
fig|6666666.60966.peg.1195 CDS 1116922 1118904 1 + 1983
FIG00858706: -none- D23_1c1201 Neut_1035 hypothetical protein
fig|6666666.60966.peg.1196 CDS 1120329 1118899 -3 - 1431 probable
integral -none- D23_1c1202 Neut_1034 membrane protein NMA1898
fig|6666666.60966.peg.1197 CDS 1121723 1120329 -2 - 1395
FIG00859415: -none- D23_1c1203 Neut_1033 hypothetical protein
fig|6666666.60966.peg.1198 CDS 1121909 1121763 -2 - 147
hypothetical protein -none- D23_1c1204 NA
fig|6666666.60966.peg.1199 CDS 1121985 1122698 3 + 714 COGs COG0518
-none- D23_1c1205 Neut_1032 fig|6666666.60966.peg.1200 CDS 1123590
1122748 -3 - 843 RNA polymerase sigma Heat shock Cell division
D23_1c1206 Neut_1031 factor RpoH Proteases and a Methyltransferase;
<br>Heat shock dnaK gene cluster extended;
<br>Transcription initiation, bacterial sigma factors
fig|6666666.60966.peg.1201 CDS 1124005 1124823 1 + 819 Cytochrome c
family -none- D23_1c1207 NA protein fig|6666666.60966.peg.1203 CDS
1125802 1127289 1 + 1488 FIG00858881: -none- D23_1c1209 Neut_1029
hypothetical protein fig|6666666.60966.peg.1204 CDS 1127318 1128325
2 + 1008 Sulfate-binding protein Inorganic Sulfur D23_1c1210
Neut_1028 Sbp Assimilation fig|6666666.60966.peg.1205 CDS 1128452
1128580 2 + 129 hypothetical protein -none- D23_1c1211 NA
fig|6666666.60966.peg.1206 CDS 1128661 1129494 1 + 834 Sulfate
transport Cysteine Biosynthesis; D23_1c1212 Neut_1026 system
permease <br>Inorganic Sulfur protein CysT Assimilation
fig|6666666.60966.peg.1207 CDS 1129502 1130371 2 + 870 Sulfate
transport Cysteine Biosynthesis; D23_1c1213 Neut_1025 system
permease <br>Inorganic Sulfur protein CysW Assimilation
fig|6666666.60966.peg.1208 CDS 1130383 1131471 1 + 1089 Sulfate and
thiosulfate Cysteine Biosynthesis; D23_1c1214 Neut_1024 import
ATP-binding <br>Inorganic Sulfur protein CysA (EC
Assimilation; 3.6.3.25) <br>Uptake of selenate and selenite
fig|6666666.60966.peg.1209 CDS 1131827 1131510 -2 - 318 possible
lipase -none- D23_1c1215 Neut_1023 fig|6666666.60966.peg.1210 CDS
1133403 1131859 -3 - 1545 Aminopeptidase PepA- -none- D23_1c1216
Neut_1022 related protein fig|6666666.60966.peg.1211 CDS 1133455
1134249 1 + 795 Thymidylate
synthase Folate Biosynthesis; D23_1c1217 Neut_1021 (EC 2.1.1.45)
<br>pyrimidine conversions fig|6666666.60966.peg.1212 CDS
1134246 1134776 3 + 531 Dihydrofolate reductase 5-FCL-like protein;
D23_1c1218 Neut_1020 (EC 1.5.1.3) <br>EC49-61;
<br>Folate Biosynthesis fig|6666666.60966.peg.1213 CDS
1136053 1134809 -1 - 1245 Response regulator -none- D23_1c1219
Neut_1019 fig|6666666.60966.peg.1215 CDS 1136321 1136785 2 + 465
Mobile element protein -none- D23_1c1220 Neut_0357
fig|6666666.60966.peg.1216 CDS 1136808 1137512 3 + 705 Mobile
element protein -none- D23_1c1221 Neut_1318
fig|6666666.60966.peg.1217 CDS 1137576 1138703 3 + 1128 Catalase
(EC 1.11.1.6) Oxidative stress; D23_1c1222 NA
<br>Photorespiration (oxidative C2cycle);
<br>Protection from Reactive Oxygen Species
fig|6666666.60966.peg.1218 CDS 1139453 1138773 -2 - 681 Mobile
element protein -none- D23_1c1223 Neut_1318
fig|6666666.60966.peg.1219 CDS 1139703 1139837 3 + 135 Mobile
element protein -none- D23_1c1224 Neut_2500
fig|6666666.60966.peg.1220 CDS 1139894 1140238 2 + 345 Mobile
element protein -none- D23_1c1225 Neut_1375
fig|6666666.60966.peg.1221 CDS 1141157 1140195 -2 - 963 Mobile
element protein -none- D23_1c1226 Neut_1278
fig|6666666.60966.peg.1222 CDS 1141250 1141762 2 + 513 Mobile
element protein -none- D23_1c1227 Neut_1624
fig|6666666.60966.peg.1223 CDS 1142310 1141846 -3 - 465 Mobile
element protein -none- D23_1c1228 Neut_0357
fig|6666666.60966.peg.1224 CDS 1142882 1142409 -2 - 474 Mobile
element protein -none- D23_1c1229 Neut_0883
fig|6666666.60966.peg.1225 CDS 1144087 1143419 -1 - 669
hypothetical protein -none- D23_1c1230 NA
fig|6666666.60966.peg.1226 CDS 1144329 1144078 -3 - 252 ABC-type
antimicrobial -none- D23_1c1231 NA peptide transport system,
permease component fig|6666666.60966.peg.1227 CDS 1144623 1145231 3
+ 609 Transcriptional -none- D23_1c1232 Neut_1011 regulator, TetR
family fig|6666666.60966.peg.1228 CDS 1145317 1146351 1 + 1035
Predicted membrane ATP-dependent efflux D23_1c1233 Neut_1010 fusion
protein (MFP) pump transporter Ybh component of efflux pump,
membrane anchor protein YbhG fig|6666666.60966.peg.1229 CDS 1146341
1148125 2 + 1785 ABC transporter ATP-dependent efflux D23_1c1234
Neut_1009 multidrug efflux pump, pump transporter Ybh fused
ATP-binding domains fig|6666666.60966.peg.1230 CDS 1148122 1149270
1 + 1149 ABC transport system, ATP-dependent efflux D23_1c1235
Neut_1008 permease component pump transporter Ybh YbhS
fig|6666666.60966.peg.1231 CDS 1149276 1150400 3 + 1125 ABC
transport system, ATP-dependent efflux D23_1c1236 Neut_1007
permease component pump transporter Ybh YbhR
fig|6666666.60966.peg.1232 CDS 1150415 1150546 2 + 132 hypothetical
protein -none- D23_1c1237 NA fig|6666666.60966.peg.1233 CDS 1150719
1150507 -3 - 213 hypothetical protein -none- D23_1c1238 NA
fig|6666666.60966.peg.1234 CDS 1150690 1150875 1 + 186 hypothetical
protein -none- D23_1c1239 Neut_1006 fig|6666666.60966.peg.1235 CDS
1150882 1151043 1 + 162 hypothetical protein -none- D23_1c1240 NA
fig|6666666.60966.peg.1236 CDS 1151054 1151923 2 + 870 hypothetical
protein -none- D23_1c1241 Neut_1006 fig|6666666.60966.peg.1237 CDS
1151916 1152278 3 + 363 hypothetical protein -none- D23_1c1242 NA
fig|6666666.60966.peg.1239 CDS 1152362 1152703 2 + 342 hypothetical
protein -none- D23_1c1243 Neut_1005 fig|6666666.60966.peg.1240 CDS
1153760 1152756 -2 - 1005 Mobile element protein -none- D23_1c1244
Neut_1862 fig|6666666.60966.peg.1241 CDS 1153821 1154177 3 + 357
Putative transport -none- D23_1c1245 Neut_1004 system permease
protein fig|6666666.60966.peg.1242 CDS 1154289 1154441 3 + 153
FIG00626672: -none- D23_1c1246 Neut_1003 hypothetical protein
fig|6666666.60966.peg.1243 CDS 1154607 1154476 -3 - 132
hypothetical protein -none- D23_1c1247 Neut_1226
fig|6666666.60966.peg.1244 CDS 1156287 1154728 -3 - 1560 amino acid
transporter -none- D23_1c1248 Neut_1227 fig|6666666.60966.peg.1245
CDS 1157495 1156611 -2 - 885 DNA recombination- DNA repair,
bacterial D23_1c1250 Neut_1228 dependent growth factor C
fig|6666666.60966.peg.1246 CDS 1158541 1157738 -1 - 804 Probable
component of Lipopolysaccharide D23_1c1252 Neut_1229 the
lipoprotein assembly assembly complex (forms a complex with YaeT,
YfgL, and NlpB) fig|6666666.60966.peg.1247 CDS 1158543 1159571 3 +
1029 Ribosomal large subunit RNA pseudouridine D23_1c1253 Neut_1230
pseudouridine synthase syntheses; D (EC 4.2.1.70)
<br>Ribosome biogenesis bacterial fig|6666666.60966.peg.1248
CDS 1159795 1161201 1 + 1407 Glutamine synthetase Ammonia
assimilation; D23_1c1254 Neut_1231 type I (EC 6.3.1.2)
<br>Glutamine, Glutamate, Aspartate and Asparagine
Biosynthesis; <br>Glutamine synthetases;
<br>Peptidoglycan Biosynthesis fig|6666666.60966.peg.1249 CDS
1161356 1161826 2 + 471 FIG00858905: -none- D23_1c1256 Neut_1232
hypothetical protein fig|6666666.60966.peg.1250 CDS 1161926 1161813
-2 - 114 hypothetical protein -none- D23_1c1257 NA
fig|6666666.60966.peg.1251 CDS 1162096 1162263 1 + 168 hypothetical
protein -none- D23_1c1258 NA fig|6666666.60966.peg.1252 CDS 1162260
1162415 3 + 156 hypothetical protein -none- D23_1c1259 NA
fig|6666666.60966.peg.1253 CDS 1162412 1163191 2 + 780 Putative
sulfate Inorganic Sulfur D23_1c1260 Neut_1235 permease Assimilation
fig|6666666.60966.peg.1254 CDS 1163827 1163267 -1 - 561 Iron-sulfur
cluster -none- D23_1c1261 Neut_1236 assembly scaffold protein
IscU/NifU-like for SUF system, SufE3 fig|6666666.60966.peg.1255 CDS
1164319 1163837 -1 - 483 Putative iron-sulfur -none- D23_1c1262
Neut_1237 cluster assembly scaffold protein for SUF system, SufE2
fig|6666666.60966.peg.1256 CDS 1165584 1164316 -3 - 1269 Cysteine
desulfurase Alanine biosynthesis; D23_1c1263 Neut_1238 (EC
2.8.1.7), SufS <br>mnm5U34 subfamily biosynthesis bacteria;
<br>tRNA modification Bacteria fig|6666666.60966.peg.1257 CDS
1166895 1165588 -3 - 1308 Iron-sulfur cluster CBSS- D23_1c1264
Neut_1239 assembly protein SufD 196164.1.peg.1690; <br>tRNA
modification Bacteria fig|6666666.60966.peg.1258 CDS 1167683
1166892 -2 - 792 Iron-sulfur cluster CBSS- D23_1c1265 Neut_1240
assembly ATPase 196164.1.peg.1690; protein SufC <br>tRNA
modification Bacteria fig|6666666.60966.peg.1259 CDS 1169116
1167680 -1 - 1437 Iron-sulfur cluster CBSS- D23_1c1266 Neut_1241
assembly protein SufB 196164.1.peg.1690; <br>tRNA
modification Bacteria fig|6666666.60966.peg.1260 CDS 1169465
1169136 -2 - 330 Iron binding protein Alanine biosynthesis;
D23_1c1267 Neut_1242 IscA for iron-sulfur <br>tRNA
modification cluster assembly Bacteria fig|6666666.60966.peg.1261
CDS 1169958 1169491 -3 - 468 Iron-sulfur cluster Alanine
biosynthesis; D23_1c1268 Neut_1243 regulator IscR <br>Rrf2
family transcriptional regulators fig|6666666.60966.peg.1262 CDS
1170306 1171838 3 + 1533 2-isopropylmalate Branched-Chain Amino
D23_1c1270 Neut_1244 synthase (EC 2.3.3.13) Acid Biosynthesis;
<br>Leucine Biosynthesis fig|6666666.60966.peg.1263 CDS
1171964 1172467 2 + 504 Cytochrome c-type Biogenesis of c-type
D23_1c1271 Neut_1245 biogenesis protein ResA cytochromes
fig|6666666.60966.peg.1264 CDS 1173081 1172488 -3 - 594 FIG016425:
Soluble lytic -none- D23_1c1272 Neut_1246 murein transglycosylase
and related regulatory proteins (some contain LysM/invasin domains)
fig|6666666.60966.peg.1265 CDS 1174775 1173069 -2 - 1707
Prolyl-tRNA synthetase tRNA aminoacylation, D23_1c1273 Neut_1247
(EC 6.1.1.15), bacterial Pro type fig|6666666.60966.peg.1266 CDS
1175004 1175567 3 + 564 Adenosine (5')- CBSS- D23_1c1274 Neut_1248
pentaphospho- 364106.7.peg.3204; (5'')- <br>Nudix proteins
adenosine (nucleoside triphosphate pyrophosphohydrolase
hydrolases); (EC 3.6.1.--) <br>Phosphoglycerate mutase
protein family fig|6666666.60966.peg.1267 CDS 1175673 1176677 3 +
1005 Cytochrome c551 Protection from Reactive D23_1c1275 Neut_1249
peroxidase (EC 1.11.1.5) Oxygen Species fig|6666666.60966.peg.1269
CDS 1176892 1178190 1 + 1299 Sensor histidine kinase Global
Two-component D23_1c1276 Neut_1250 PrrB (RegB) (EC 2.7.3.--)
Regulator PrrBA in Proteobacteria fig|6666666.60966.peg.1270 CDS
1178205 1178750 3 + 546 Dna binding response Global Two-component
D23_1c1277 Neut_1251 regulator PrrA (RegA) Regulator PrrBA in
Proteobacteria fig|6666666.60966.peg.1271 CDS 1181021 1178853 -2 -
2169 Ferrichrome-iron -none- D23_1c1278 Neut_1252 receptor
fig|6666666.60966.peg.1272 CDS 1181355 1181558 3 + 204 hypothetical
protein -none- D23_1c1279 NA fig|6666666.60966.peg.1273 CDS 1181609
1181776 2 + 168 hypothetical protein -none- D23_1c1280 NA
fig|6666666.60966.peg.1274 CDS 1181748 1181981 3 + 234 Mobile
element protein -none- D23_1c1281 NA fig|6666666.60966.peg.1275 CDS
1182136 1181990 -1 - 147 hypothetical protein -none- D23_1c1282 NA
fig|6666666.60966.peg.1277 CDS 1182799 1182386 -1 - 414
hypothetical protein -none- D23_1c1283 Neut_1254
fig|6666666.60966.peg.1278 CDS 1182892 1183920 1 + 1029 Mobile
element protein -none- D23_1c1284 Neut_1746
fig|6666666.60966.peg.1280 CDS 1185348 1184569 -3 - 780
CDP-diacylglycerol-- Glycerolipid and D23_1c1285 Neut_1258 serine
O- Glycerophospholipid phosphatidyltransferase Metabolism in
Bacteria (EC 2.7.8.8) fig|6666666.60966.peg.1281 CDS 1186028
1185378 -2 - 651 Phosphatidylserine Glycerolipid and D23_1c1286
Neut_1259 decarboxylase (EC Glycerophospholipid 4.1.1.65)
Metabolism in Bacteria fig|6666666.60966.peg.1282 CDS 1187049
1186033 -3 - 1017 Ketol-acid Branched-Chain Amino D23_1c1287
Neut_1260 reductoisomerase (EC Acid Biosynthesis; 1.1.1.86)
<br>Coenzyme A Biosynthesis fig|6666666.60966.peg.1283 CDS
1187629 1187138 -1 - 492 Acetolactate synthase Acetolactate
synthase D23_1c1288 Neut_1261 small subunit (EC subunits;
<br>Branched- 2.2.1.6) Chain Amino Acid Biosynthesis
fig|6666666.60966.peg.1284 CDS 1189337 1187634 -2 - 1704
Acetolactate synthase Acetolactate synthase D23_1c1289 Neut_1262
large subunit (EC subunits; <br>Branched- 2.2.1.6) Chain
Amino Acid Biosynthesis fig|6666666.60966.peg.1285 CDS 1189440
1189327 -3 - 114 hypothetical protein -none- D23_1c1290 NA
fig|6666666.60966.peg.1287 CDS 1191111 1189663 -3 - 1449 TldD
protein, part of CBSS-316057.3.peg.563; D23_1c1292 Neut_1263
TldE/TldD proteolytic <br>CBSS- complex 354.1.peg.2917;
<br>Putative TldE-TldD proteolytic complex
fig|6666666.60966.peg.1288 CDS 1192101 1191238 -3 - 864
FIG003879:
Predicted CBSS-354.1.peg.2917 D23_1c1293 Neut_1264 amidohydrolase/
Aliphatic amidase AmiE (EC 3.5.1.4) fig|6666666.60966.peg.1289 CDS
1196193 1192303 -3 - 3891 FIG005080: Possible CBSS-354.1.peg.2917
D23_1c1294 Neut_1265 exported protein fig|6666666.60966.peg.1290
CDS 1196421 1199210 3 + 2790 Glutamate-ammonia- Ammonia
assimilation; D23_1c1295 Neut_1266 ligase <br>CBSS-
adenylyltransferase (EC 316057.3.peg.3521 2.7.7.42)
fig|6666666.60966.peg.1291 CDS 1200720 1200058 -3 - 663
FIG00859512: -none- D23_1c1300 Neut_1268 hypothetical protein
fig|6666666.60966.peg.1292 CDS 1200901 1200761 -1 - 141
hypothetical protein -none- D23_1c1301 NA
fig|6666666.60966.peg.1293 CDS 1200921 1202306 3 + 1386
Argininosuccinate lyase Arginine Biosynthesis-- D23_1c1302
Neut_1269 (EC 4.3.2.1) gjo; <br>Arginine Biosynthesis
extended fig|6666666.60966.peg.1294 CDS 1202336 1203241 2 + 906
Ribulosamine/erythrulosamine Protein deglycation D23_1c1303
Neut_1270 3-kinase potentially involved in protein deglycation
fig|6666666.60966.peg.1295 CDS 1203386 1204876 2 + 1491
FIG00807778: -none- D23_1c1304 Neut_1271 hypothetical protein
fig|6666666.60966.peg.1297 CDS 1205984 1205553 -2 - 432
hypothetical protein -none- D23_1c1305 Neut_1272
fig|6666666.60966.peg.1298 CDS 1206313 1205987 -1 - 327
hypothetical protein -none- D23_1c1306 Neut_1273
fig|6666666.60966.peg.1299 CDS 1206643 1206329 -1 - 315 CrcB
protein -none- D23_1c1307 Neut_1274 fig|6666666.60966.peg.1300 CDS
1206663 1206902 3 + 240 hypothetical protein -none- D23_1c1308 NA
fig|6666666.60966.peg.1301 CDS 1207586 1206945 -2 - 642 Chemotaxis
response- -none- D23_1c1309 Neut_1275 phosphatase CheZ
fig|6666666.60966.peg.1302 CDS 1208030 1207635 -2 - 396 Chemotaxis
regulator- Flagellar motility D23_1c1310 Neut_1276 transmits
chemoreceptor signals to flagelllar motor components CheY
fig|6666666.60966.peg.1303 CDS 1209139 1208375 -1 - 765 Mobile
element protein -none- D23_1c1311 NA fig|6666666.60966.peg.1305 CDS
1210466 1210134 -2 - 333 hypothetical protein -none- D23_1c1313 NA
fig|6666666.60966.peg.1306 CDS 1210482 1210661 3 + 180 hypothetical
protein -none- D23_1c1314 Neut_1280 fig|6666666.60966.peg.1307 CDS
1212693 1210768 -3 - 1926 Cytochrome c, class I -none- D23_1c1315
Neut_1281 fig|6666666.60966.peg.1308 CDS 1213523 1213044 -2 - 480
FIG00858481: -none- D23_1c1317 Neut_1282 hypothetical protein
fig|6666666.60966.peg.1309 CDS 1213544 1214608 2 + 1065
Folate-dependent -none- D23_1c1318 Neut_1283 protein for Fe/S
cluster synthesis/repair in oxidative stress
fig|6666666.60966.peg.1310 CDS 1215290 1214631 -2 - 660 FOG:
Ankyrin repeat -none- D23_1c1319 Neut_1284
fig|6666666.60966.peg.1311 CDS 1215984 1215292 -3 - 693 Putative
YcfH D23_1c1320 Neut_1285 deoxyribonuclease YcfH
fig|6666666.60966.peg.1313 CDS 1216517 1216125 -2 - 393 Queuosine
biosynthesis Queuosine-Archaeosine D23_1c1321 Neut_1286 QueD,
PTPS-I Biosynthesis; <br>Zinc regulated enzymes;
<br>tRNA modification Bacteria fig|6666666.60966.peg.1315 CDS
1216624 1217484 1 + 861 Radical SAM domain -none- D23_1c1322
Neut_1287 protein fig|6666666.60966.peg.1316 CDS 1217801 1217514 -2
- 288 FIG00858571: -none- D23_1c1323 Neut_1288 hypothetical protein
fig|6666666.60966.peg.1318 CDS 1219170 1218214 -3 - 957
Cobalt-zinc-cadmium Cobalt-zinc-cadmium D23_1c1325 Neut_1289
resistance protein CzcD resistance fig|6666666.60966.peg.1319 CDS
1221684 1219195 -3 - 2490 Lead, cadmium, zinc Copper Transport
D23_1c1326 Neut_1290 and mercury System; <br>Copper
transporting ATPase (EC homeostasis 3.6.3.3) (EC 3.6.3.5);
Copper-translocating P- type ATPase (EC 3.6.3.4)
fig|6666666.60966.peg.1320 CDS 1223842 1221797 -1 - 2046
1,4-alpha-glucan Glycogen metabolism D23_1c1327 Neut_1291
(glycogen) branching enzyme, GH-13-type (EC 2.4.1.18)
fig|6666666.60966.peg.1321 CDS 1223815 1224054 1 + 240 hypothetical
protein -none- D23_1c1328 NA fig|6666666.60966.peg.1322 CDS 1224141
1225418 3 + 1278 Glucose-1-phosphate Glycogen metabolism D23_1c1329
Neut_1292 adenylyltransferase (EC 2.7.7.27)
fig|6666666.60966.peg.1323 CDS 1225484 1227202 2 + 1719
Amylopullulanase (EC -none- D23_1c1330 Neut_1293 3.2.1.1)/(EC
3.2.1.41) fig|6666666.60966.peg.1324 CDS 1227268 1229292 1 + 2025
Alpha-amylase (EC -none- D23_1c1331 Neut_1294 3.2.1.1)
fig|6666666.60966.peg.1325 CDS 1229324 1232014 2 + 2691
hypothetical protein -none- D23_1c1332 Neut_1295
fig|6666666.60966.peg.1326 CDS 1232973 1232236 -3 - 738 Uracil-DNA
glycosylase, Uracil-DNA glycosylase D23_1c1334 Neut_1296 family 4
fig|6666666.60966.peg.1327 CDS 1233520 1233032 -1 - 489
Ribosomal-protein- Bacterial RNA- D23_1c1335 Neut_1297 S18p-alanine
metabolizing Zn- acetyltransferase (EC dependent hydrolases;
2.3.1.--) <br>Ribosome biogenesis bacterial
fig|6666666.60966.peg.1328 CDS 1234194 1233523 -3 - 672 Inactive
homolog of -none- D23_1c1336 Neut_1298 metal-dependent proteases,
putative molecular chaperone fig|6666666.60966.peg.1329 CDS 1234742
1234209 -2 - 534 2'-5' RNA RNA processing orphans D23_1c1337
Neut_1299 ligase fig|6666666.60966.peg.1330 CDS 1235245 1234742 -1
- 504 2-C-methyl-D-erythritol Isoprenoid Biosynthesis; D23_1c1338
Neut_1300 2,4-cyclodiphosphate <br>Nonmevalonate synthase (EC
4.6.1.12) Branch of Isoprenoid Biosynthesis; <br>Possible RNA
degradation cluster; <br>Stationary phase repair cluster
fig|6666666.60966.peg.1331 CDS 1235544 1235356 -3 - 189
hypothetical protein -none- D23_1c1339 Neut_0314
fig|6666666.60966.peg.1332 CDS 1235706 1235566 -3 - 141
hypothetical protein -none- D23_1c1340 Neut_0314
fig|6666666.60966.peg.1335 CDS 1236565 1236008 -1 - 558 Translation
elongation Translation elongation D23_1c1341 Neut_1302 factor P
factors bacterial fig|6666666.60966.peg.1336 CDS 1237794 1236640 -3
- 1155 hypothetical protein -none- D23_1c1342 Neut_1303
fig|6666666.60966.peg.1337 CDS 1237927 1238928 1 + 1002 D-lactate
Fermentations: Lactate D23_1c1343 Neut_1304 dehydrogenase (EC
1.1.1.28) fig|6666666.60966.peg.1338 CDS 1240296 1239037 -3 - 1260
putative membrane -none- D23_1c1344 Neut_1315 protein
fig|6666666.60966.peg.1339 CDS 1241400 1240354 -3 - 1047 Peptide
chain release Programmed frameshift; D23_1c1345 Neut_1316 factor 2;
programmed <br>Programmed frameshift-containing frameshift;
<br>Translation termination factors bacterial
fig|6666666.60966.peg.1340 CDS 1243378 1241576 -1 - 1803 patatin
family protein -none- D23_1c1346 Neut_1317
fig|6666666.60966.peg.1341 CDS 1244736 1243531 -3 - 1206 Catalase
(EC 1.11.1.6) Oxidative stress; D23_1c1348 NA
<br>Photorespiration (oxidative C2 cycle);
<br>Protection from Reactive Oxygen Species
fig|6666666.60966.peg.1342 CDS 1246268 1244739 -2 - 1530 Peroxidase
(EC 1.11.1.7) Oxidative stress; D23_1c1349 NA <br>Protection
from Reactive Oxygen Species fig|6666666.60966.peg.1343 CDS 1247585
1246281 -2 - 1305 Peroxidase (EC 1.11.1.7) Oxidative stress;
D23_1c1350 NA <br>Protection from Reactive Oxygen Species
fig|6666666.60966.peg.1344 CDS 1248078 1247623 -3 - 456
hypothetical protein -none- D23_1c1351 NA
fig|6666666.60966.peg.1345 CDS 1248448 1251117 1 + 2670
FIG00860108: -none- D23_1c1352 Neut_0141 hypothetical protein
fig|6666666.60966.peg.1346 CDS 1251218 1253155 2 + 1938 Choline
dehydrogenase -none- D23_1c1353 NA (EC 1.1.99.1)
fig|6666666.60966.peg.1347 CDS 1256051 1253184 -2 - 2868 Peroxidase
(EC 1.11.1.8) -none- D23_1c1354 NA fig|6666666.60966.peg.1348 CDS
1257505 1256081 -1 - 1425 Hemagglutinin -none- D23_1c1355 NA
fig|6666666.60966.peg.1349 CDS 1258257 1257547 -3 - 711
hypothetical protein -none- D23_1c1356 NA
fig|6666666.60966.peg.1350 CDS 1259233 1258262 -1 - 972
hypothetical protein -none- D23_1c1357 NA
fig|6666666.60966.peg.1351 CDS 1261078 1259246 -1 - 1833
hypothetical protein -none- D23_1c1358 NA
fig|6666666.60966.peg.1352 CDS 1262776 1261109 -1 - 1668
Arachidonate 15- -none- D23_1c1359 NA lipoxygenase (EC 1.13.11.33)
fig|6666666.60966.peg.1353 CDS 1264449 1262845 -3 - 1605 putative
-none- D23_1c1360 NA cyclooxygenase-2 fig|6666666.60966.peg.1354
CDS 1266134 1264638 -2 - 1497 hypothetical protein -none-
D23_1c1361 NA fig|6666666.60966.peg.1355 CDS 1266382 1266167 -1 -
216 hypothetical protein -none- D23_1c1362 NA
fig|6666666.60966.peg.1356 CDS 1266704 1266444 -2 - 261
hypothetical protein -none- D23_1c1363 NA
fig|6666666.60966.peg.1357 CDS 1267804 1266983 -1 - 822 Kazal-type
serine -none- D23_1c1364 NA protease inhibitor domain
fig|6666666.60966.peg.1358 CDS 1268650 1267970 -1 - 681 Kazal-type
serine -none- D23_1c1365 NA protease inhibitor domain
fig|6666666.60966.peg.1359 CDS 1268913 1268800 -3 - 114
hypothetical protein -none- D23_1c1366 NA
fig|6666666.60966.peg.1360 CDS 1269830 1269126 -2 - 705 Mobile
element protein -none- D23_1c1367 Neut_1318
fig|6666666.60966.peg.1361 CDS 1270083 1269853 -3 - 231 Mobile
element protein -none- D23_1c1368 Neut_1318
fig|6666666.60966.peg.1362 CDS 1270317 1270111 -3 - 207 Mobile
element protein -none- D23_1c1369 Neut_2405
fig|6666666.60966.peg.1363 CDS 1271332 1270409 -1 - 924 alpha/beta
hydrolase -none- D23_1c1370 NA fold fig|6666666.60966.peg.1364 CDS
1271721 1271329 -3 - 393 hypothetical protein -none- D23_1c1371 NA
fig|6666666.60966.peg.1365 CDS 1272160 1273251 1 + 1092 Putrescine
transport Polyamine Metabolism D23_1c1372 Neut_1328 ATP-binding
protein PotA (TC 3.A.1.11.1) fig|6666666.60966.peg.1366 CDS 1273248
1274150 3 + 903 Spermidine Putrescine Polyamine Metabolism
D23_1c1373 Neut_1329 ABC transporter permease component PotB (TC
3.A.1.11.1) fig|6666666.60966.peg.1367 CDS 1274170 1274955 1 + 786
Spermidine Putrescine Polyamine Metabolism D23_1c1374 Neut_1330 ABC
transporter permease component potC (TC_3.A.1.11.1)
fig|6666666.60966.peg.1368 CDS 1274952 1276061 3 + 1110 ABC
transporter, Polyamine Metabolism D23_1c1375 Neut_1331 periplasmic
spermidine putrescine-binding protein PotD (TC 3.A.1.11.1)
fig|6666666.60966.peg.1369 CDS 1276066 1276374 1 + 309 Ferredoxin,
2Fe--2S Alanine biosynthesis; D23_1c1376 Neut_1332
<br>Soluble cytochromes and functionally related electron
carriers;
<br>tRNA modification Bacteria fig|6666666.60966.peg.1370 CDS
1278030 1276423 -3 - 1608 Type I restriction-
Restriction-Modification D23_1c1377 Neut_0541 modification system,
System; <br>Type I DNA-methyltransferase
Restriction-Modification subunit M (EC 2.1.1.72)
fig|6666666.60966.peg.1371 CDS 1279031 1278027 -2 - 1005 Putative
DNA-binding Restriction-Modification D23_1c1378 NA protein in
cluster with System Type I restriction- modification system
fig|6666666.60966.peg.1372 CDS 1282963 1279028 -1 - 3936 Type I
restriction- Restriction-Modification D23_1c1379 Neut_0537
modification system, System; <br>Type I restriction subunit R
(EC Restriction-Modification 3.1.21.3) fig|6666666.60966.peg.1373
CDS 1283272 1282982 -1 - 291 Type I restriction-
Restriction-Modification D23_1c1380 NA modification system, System;
<br>Type I restriction subunit R (EC Restriction-Modification
3.1.21.3) fig|6666666.60966.peg.1374 CDS 1287342 1283581 -3 - 3762
macromolecule -none- D23_1c1381 Neut_1336 metabolism; macromolecule
synthesis, modification; dna-replication, repair, restr./modif.
fig|6666666.60966.peg.1375 CDS 1287828 1287349 -3 - 480
FIG00858549: -none- D23_1c1382 Neut_1337 hypothetical protein
fig|6666666.60966.peg.1376 CDS 1288968 1287859 -3 - 1110
2-keto-3-deoxy-D- Chorismate Synthesis; D23_1c1383 Neut_1338
arabino-heptulosonate- <br>Common Pathway 7-phosphate
synthase I For Synthesis of alpha (EC 2.5.1.54) Aromatic Compounds
(DAHP synthase to chorismate) fig|6666666.60966.peg.1377 CDS
1290768 1289113 -3 - 1656 MutS domain protein, DNA repair,
bacterial D23_1c1384 Neut_1339 family 6 MutL-MutS system
fig|6666666.60966.peg.1378 CDS 1290915 1291493 3 + 579 FIG00858435:
-none- D23_1c1385 Neut_1340 hypothetical protein
fig|6666666.60966.peg.1379 CDS 1291506 1292660 3 + 1155 Probable
Co/Zn/Cd Cobalt-zinc-cadmium D23_1c1386 Neut_1341 efflux system
resistance membrane fusion protein fig|6666666.60966.peg.1380 CDS
1292693 1293328 2 + 636 ABC transporter ATP- -none- D23_1c1387
Neut_1342 binding protein YvcR fig|6666666.60966.peg.1381 CDS
1293325 1294527 1 + 1203 ABC transporter -none- D23_1c1388
Neut_1343 permease protein fig|6666666.60966.peg.1382 CDS 1294533
1295732 3 + 1200 putative ABC -none- D23_1c1389 Neut_1344
transporter protein fig|6666666.60966.peg.1383 CDS 1296266 1295742
-2 - 525 FIG00859169: -none- D23_1c1390 Neut_1345 hypothetical
protein fig|6666666.60966.peg.1385 CDS 1296862 1297086 1 + 225 ADA
regulatory protein/ DNA repair, bacterial; D23_1c1391 Neut_1346
Methylated-DNA-- <br>DNA repair, protein-cysteine bacterial
methyltransferase (EC 2.1.1.63) fig|6666666.60966.peg.1386 CDS
1297089 1297802 3 + 714 hypothetical protein -none- D23_1c1392
Neut_1347 fig|6666666.60966.peg.1387 CDS 1298101 1297967 -1 - 135
hypothetical protein -none- D23_1c1393 NA
fig|6666666.60966.peg.1389 CDS 1298212 1298838 1 + 627 Alkylated
DNA repair -none- D23_1c1395 Neut_1349 protein
fig|6666666.60966.peg.1390 CDS 1300170 1298923 -3 - 1248 Mobile
element protein -none- D23_1c1396 Neut_0357
fig|6666666.60966.peg.1391 CDS 1300681 1300355 -1 - 327
hypothetical protein -none- D23_1c1397 Neut_1350
fig|6666666.60966.peg.1392 CDS 1301157 1300963 -3 - 195
Glutaredoxin Glutaredoxins; D23_1c1398 Neut_1351
<br>Glutathione: Redox cycle; <br>Phage DNA synthesis
fig|6666666.60966.peg.1393 CDS 1302170 1301697 -2 - 474 Mobile
element protein -none- D23_1c1399 Neut_1353
fig|6666666.60966.peg.1394 CDS 1303008 1302400 -3 - 609 Glutathione
S- Glutathione: Non-redox D23_1c1400 Neut_1354 transferase (EC
reactions 2.5.1.18) fig|6666666.60966.peg.1395 CDS 1303729 1303556
-1 - 174 hypothetical protein -none- D23_1c1402 NA
fig|6666666.60966.peg.1396 CDS 1303948 1307514 1 + 3567
Exodeoxyribonuclease V DNA repair, bacterial D23_1c1403 Neut_1355
gamma chain (EC RecBCD pathway 3.1.11.5) fig|6666666.60966.peg.1397
CDS 1307530 1311216 1 + 3687 Exodeoxyribonuclease V DNA repair,
bacterial D23_1c1404 Neut_1356 beta chain (EC 3.1.11.5) RecBCD
pathway fig|6666666.60966.peg.1398 CDS 1311213 1313258 3 + 2046
Exodeoxyribonuclease V DNA repair, bacterial D23_1c1405 Neut_1357
alpha chain (EC RecBCD pathway 3.1.11.5) fig|6666666.60966.peg.1399
CDS 1314581 1313277 -2 - 1305 Aspartyl -none- D23_1c1406 Neut_1358
aminopeptidase fig|6666666.60966.peg.1400 CDS 1315032 1314604 -3 -
429 PIN domain family -none- D23_1c1407 Neut_1359 protein
fig|6666666.60966.peg.1401 CDS 1315334 1315032 -2 - 303 DNA-binding
protein, -none- D23_1c1408 Neut_1360 CopG family
fig|6666666.60966.peg.1402 CDS 1316699 1315362 -2 - 1338 Sensor
protein PhoQ -none- D23_1c1409 Neut_1361 (EC 2.7.13.3)
fig|6666666.60966.peg.1403 CDS 1317382 1316696 -1 - 687 DNA-binding
response -none- D23_1c1410 Neut_1362 regulator
fig|6666666.60966.peg.1404 CDS 1317741 1317451 -3 - 291
hypothetical protein -none- D23_1c1411 Neut_1363
fig|6666666.60966.peg.1405 CDS 1318192 1317827 -1 - 366 Putative
metal G3E family of P-loop D23_1c1412 NA chaperone, involved in
GTPases (metallocenter Zn homeostasis, GTPase biosynthesis);
<br>Zinc of COG0523 family regulated enzymes
fig|6666666.60966.peg.1406 CDS 1318485 1319036 3 + 552 Protein of
unknown -none- D23_1c1413 Neut_1365 function DUF924
fig|6666666.60966.peg.1407 CDS 1320160 1319171 -1 - 990 Integron
integrase Integrons D23_1c1414 Neut_1366 IntlPac
fig|6666666.60966.peg.1408 CDS 1320314 1321651 2 + 1338 DNA
modification -none- D23_1c1415 NA methyltransferase
fig|6666666.60966.peg.1409 CDS 1321654 1322532 1 + 879 hypothetical
protein -none- D23_1c1416 NA fig|6666666.60966.peg.1410 CDS 1322665
1322880 1 + 216 hypothetical protein -none- D23_1c1417 NA
fig|6666666.60966.peg.1411 CDS 1323474 1324154 3 + 681 ThiJ/Pfpl
family protein -none- D23_1c1418 NA fig|6666666.60966.peg.1412 CDS
1324808 1324990 2 + 183 hypothetical protein -none- D23_1c1419 NA
fig|6666666.60966.peg.1413 CDS 1325941 1324979 -1 - 963 Mobile
element protein -none- D23_1c1420 Neut_1746
fig|6666666.60966.peg.1415 CDS 1326558 1328531 3 + 1974 Monoamine
oxidase Auxin biosynthesis; D23_1c1421 NA (1.4.3.4)
<br>Glycine and Serine Utilization; <br>Threonine
degradation fig|6666666.60966.peg.1417 CDS 1328848 1328711 -1 - 138
Mobile element protein -none- D23_1c1422 Neut_2501
fig|6666666.60966.peg.1418 CDS 1329144 1328821 -3 - 324 Mobile
element protein -none- D23_1c1423 Neut_1624
fig|6666666.60966.peg.1419 CDS 1329566 1329129 -2 - 438 Mobile
element protein -none- D23_1c1424 Neut_1888
fig|6666666.60966.peg.1420 CDS 1330200 1329892 -3 - 309 Death on
curing Phd-Doc, YdcE-YdcD D23_1c1425 NA protein, Doc toxin
toxin-antitoxin (programmed cell death) systems
fig|6666666.60966.peg.1421 CDS 1330677 1330231 -3 - 447 Prevent
host death Phd-Doc, YdcE-YdcD D23_1c1426 NA protein, Phd antitoxin
toxin-antitoxin (programmed cell death) systems
fig|6666666.60966.peg.1423 CDS 1331253 1331387 3 + 135 Mobile
element protein -none- D23_1c1427 Neut_2500
fig|6666666.60966.peg.1424 CDS 1331444 1332292 2 + 849 Mobile
element protein -none- D23_1c1428 Neut_1888
fig|6666666.60966.peg.1425 CDS 1332744 1333214 3 + 471
3-demethylubiquinone- -none- D23_1c1429 Neut_1376 9
3-methyltransferase fig|6666666.60966.peg.1426 CDS 1333410 1335026
3 + 1617 Dihydroxyacetone Dihydroxyacetone D23_1c1431 Neut_1377
kinase, ATP-dependent kinases (EC 2.7.1.29)
fig|6666666.60966.peg.1427 CDS 1335644 1335210 -2 - 435
hypothetical protein -none- D23_1c1432 Neut_1378
fig|6666666.60966.peg.1428 CDS 1339065 1335670 -3 - 3396 PDZ domain
-none- D23_1c1433 Neut_1379 fig|6666666.60966.peg.1429 CDS 1339241
1340350 2 + 1110 COGs COG0823 -none- D23_1c1435 Neut_1380
fig|6666666.60966.peg.1430 CDS 1341715 1340438 -1 - 1278 Putative
diheme Soluble cytochromes D23_1c1436 Neut_1381 cytochrome c-553
and functionally related electron carriers
fig|6666666.60966.peg.1431 CDS 1342431 1341712 -3 - 720 Probable
cytochrome c2 Soluble cytochromes D23_1c1437 Neut_1382 and
functionally related electron carriers fig|6666666.60966.peg.1432
CDS 1342445 1342963 2 + 519 FIG00859968: -none- D23_1c1438
Neut_1383 hypothetical protein fig|6666666.60966.peg.1433 CDS
1344805 1342952 -1 - 1854 Cell division protein Bacterial Cell
Division D23_1c1439 Neut_1384 FtsH (EC 3.4.24.--)
fig|6666666.60966.peg.1434 CDS 1345012 1346118 1 + 1107 S-
Glutathione-dependent D23_1c1440 Neut_1385
(hydroxymethyl)glutathione pathway of dehydrogenase (EC
formaldehyde 1.1.1.284) detoxification fig|6666666.60966.peg.1435
CDS 1346131 1347000 1 + 870 S-formylglutathione
Glutathione-dependent D23_1c1441 Neut_1386 hydrolase (EC 3.1.2.12)
pathway of formaldehyde detoxification fig|6666666.60966.peg.1436
CDS 1348436 1347264 -2 - 1173 Ornithine Arginine and Ornithine
D23_1c1442 Neut_1387 decarboxylase (EC Degradation;
4.1.1.17)/Arginine <br>Arginine and decarboxylase (EC
Ornithine Degradation; 4.1.1.19) <br>Polyamine Metabolism;
<br>Polyamine Metabolism fig|6666666.60966.peg.1437 CDS
1348961 1349230 2 + 270 FIG00858492: -none- D23_1c1443 Neut_1388
hypothetical protein fig|6666666.60966.peg.1438 CDS 1349336 1349214
-2 - 123 hypothetical protein -none- D23_1c1444 NA
fig|6666666.60966.peg.1439 CDS 1349660 1350622 2 + 963 Mobile
element protein -none- D23_1c1446 Neut_1862
fig|6666666.60966.peg.1440 CDS 1350742 1352079 1 + 1338 Ribosomal
protein S12p Methylthiotransferases; D23_1c1447 Neut_1389 Asp88 (E.
coli) <br>Ribosomal protein methylthiotransferase S12p Asp
methylthiotransferase fig|6666666.60966.peg.1441 CDS 1353046
1352255 -1 - 792 hypothetical protein -none- D23_1c1448 Neut_1390
fig|6666666.60966.peg.1442 CDS 1353301 1353618 1 + 318 Cell
division protein Bacterial Cell Division D23_1c1449 Neut_1391 BolA
fig|6666666.60966.peg.1443 CDS 1353569 1354282 2 + 714 LemA family
protein -none- D23_1c1450 Neut_1392 fig|6666666.60966.peg.1444 CDS
1354309 1355193 1 + 885 Beta-propeller domains -none- D23_1c1451
Neut_1393 of methanol dehydrogenase type fig|6666666.60966.peg.1445
CDS 1355207 1355710 2 + 504 FIG004694: -none- D23_1c1452 Neut_1394
Hypothetical protein fig|6666666.60966.peg.1446 CDS 1356010 1356513
1 + 504 DNA-directed RNA -none- D23_1c1454 Neut_1395 polymerase
specialized sigma subunit, sigma24- like fig|6666666.60966.peg.1447
CDS 1356510 1357232 3 + 723 FIG00859011: -none- D23_1c1455
Neut_1396 hypothetical protein fig|6666666.60966.peg.1448 CDS
1357326 1359644 3 + 2319 ABC transporter,
-none- D23_1c1456 Neut_1397 transmembrane region: ABC transporter
related fig|6666666.60966.peg.1449 CDS 1359641 1360108 2 + 468
DUF1854 domain- -none- D23_1c1457 Neut_1398 containing protein
fig|6666666.60966.peg.1451 CDS 1360927 1362021 1 + 1095
hypothetical protein -none- D23_1c1458 Neut_1860
fig|6666666.60966.peg.1452 CDS 1362049 1362342 1 + 294 Mobile
element protein -none- D23_1c1459 Neut_1719
fig|6666666.60966.peg.1453 CDS 1362441 1363319 3 + 879 Mobile
element protein -none- D23_1c1460 Neut_1720
fig|6666666.60966.peg.1454 CDS 1363397 1365250 2 + 1854
hypothetical protein -none- D23_1c1461 NA
fig|6666666.60966.peg.1455 CDS 1365453 1365262 -3 - 192 Mobile
element protein -none- D23_1c1462 Neut_2502
fig|6666666.60966.peg.1456 CDS 1365648 1367945 3 + 2298 Cyanophycin
synthase Cyanophycin D23_1c1463 Neut_1401 (EC 6.3.2.29)(EC
Metabolism 6.3.2.30) fig|6666666.60966.peg.1457 CDS 1367966 1370572
2 + 2607 Cyanophycin synthase Cyanophycin D23_1c1464 Neut_1402 (EC
6.3.2.29)(EC Metabolism 6.3.2.30) fig|6666666.60966.peg.1458 CDS
1371664 1370720 -1 - 945 Copper-containing Denitrification;
D23_1c1465 Neut_1403 nitrite reductase (EC <br>Denitrifying
1.7.2.1) reductase gene clusters fig|6666666.60966.peg.1459 CDS
1372091 1371708 -2 - 384 cytochrome c, class IC -none- D23_1c1466
Neut_1404 fig|6666666.60966.peg.1460 CDS 1372789 1372091 -1 - 699
Cytochrome c, class I -none- D23_1c1467 Neut_1405
fig|6666666.60966.peg.1461 CDS 1373888 1372827 -2 - 1062
Multicopper oxidase Copper homeostasis D23_1c1468 Neut_1406
fig|6666666.60966.peg.1462 CDS 1374021 1374137 3 + 117 hypothetical
protein -none- D23_1c1469 NA fig|6666666.60966.peg.1463 CDS 1374189
1374653 3 + 465 Nitrite-sensitive Nitrosative stress; D23_1c1470
Neut_1407 transcriptional <br>Oxidative stress; repressor
NsrR <br>Rrf2 family transcriptional regulators
fig|6666666.60966.peg.1464 CDS 1378537 1374641 -1 - 3897
FIG00858660: -none- D23_1c1471 Neut_1408 hypothetical protein
fig|6666666.60966.peg.1465 CDS 1380248 1378539 -2 - 1710 Outer
membrane -none- D23_1c1472 Neut_1409 protein
fig|6666666.60966.peg.1466 CDS 1380471 1380340 -3 - 132
hypothetical protein -none- D23_1c1473 NA
fig|6666666.60966.peg.1467 CDS 1380491 1381141 2 + 651 Uracil-DNA
glycosylase, Uracil-DNA glycosylase D23_1c1474 Neut_1410 family 5
fig|6666666.60966.peg.1468 CDS 1381162 1381350 1 + 189 putative
isomerase -none- D23_1c1475 Neut_1411 fig|6666666.60966.peg.1469
CDS 1381364 1383178 2 + 1815 Excinuclease ABC DNA repair, UvrABC
D23_1c1476 Neut_1412 subunit C system fig|6666666.60966.peg.1470
CDS 1383321 1384283 3 + 963 Mobile element protein -none-
D23_1c1477 Neut_1746 fig|6666666.60966.peg.1471 CDS 1384401 1384814
3 + 414 ABC-type multidrug CBSS-196164.1.peg.1690 D23_1c1478 NA
transport system, permease component fig|6666666.60966.peg.1472 CDS
1384811 1385149 2 + 339 ABC-type multidrug CBSS-196164.1.peg.1690
D23_1c1479 NA transport system, permease component
fig|6666666.60966.peg.1474 CDS 1385894 1388275 2 + 2382 Penicillin
acylase II -none- D23_1c1480 Neut_1415 fig|6666666.60966.peg.1475
CDS 1388559 1388395 -3 - 165 hypothetical protein -none- D23_1c1481
NA fig|6666666.60966.peg.1476 CDS 1388615 1389973 2 + 1359 Response
regulatory -none- D23_1c1482 Neut_1416 protein
fig|6666666.60966.peg.1477 CDS 1390014 1391603 3 + 1590
Long-chain-fatty-acid-- Biotin biosynthesis; D23_1c1483 Neut_1417
CoAligase (EC 6.2.1.3) <br>Biotin synthesis cluster;
<br>Fatty acid metabolism cluster fig|6666666.60966.peg.1478
CDS 1391630 1392835 2 + 1206 Diaminopimelate Lysine Biosynthesis
DAP D23_1c1484 Neut_1418 decarboxylase (EC Pathway, GJO scratch
4.1.1.20) fig|6666666.60966.peg.1479 CDS 1392996 1394843 3 + 1848
Asparagine synthetase Cyanophycin D23_1c1485 Neut_1419
[glutamine-hydrolyzing] Metabolism; (EC 6.3.5.4)
<br>Glutamate and Aspartate uptake in Bacteria;
<br>Glutamine, Glutamate, Aspartate and Asparagine
Biosynthesis fig|6666666.60966.peg.1480 CDS 1394795 1394911 2 + 117
hypothetical protein -none- D23_1c1486 NA
fig|6666666.60966.peg.1482 CDS 1395163 1395975 1 + 813 FIG00858746:
-none- D23_1c1488 Neut_1420 hypothetical protein
fig|6666666.60966.peg.1483 CDS 1397102 1396140 -2 - 963 Mobile
element protein -none- D23_1c1490 Neut_1746
fig|6666666.60966.peg.1484 CDS 1397178 1397462 3 + 285 COGs COG0226
-none- D23_1c1491 Neut_1423 fig|6666666.60966.peg.1485 CDS 1397455
1398681 1 + 1227 FIG00859800: -none- D23_1c1492 Neut_1424
hypothetical protein fig|6666666.60966.peg.1486 CDS 1398693 1401635
3 + 2943 diguanylate -none- D23_1c1493 Neut_1425
cyclase/phosphodiesterase (GGDEF & EAL domains) with PAS/PAC
sensor(s) fig|6666666.60966.peg.1488 CDS 1402082 1401924 -2 - 159
hypothetical protein -none- D23_1c1494 NA
fig|6666666.60966.peg.1489 CDS 1402531 1402115 -1 - 417 OsmC/Ohr
family -none- D23_1c1495 Neut_1426 protein
fig|6666666.60966.peg.1490 CDS 1403584 1402532 -1 - 1053 DNA
polymerase III CBSS-208964.1.peg.3988 D23_1c1496 Neut_1427 delta
subunit (EC 2.7.7.7) fig|6666666.60966.peg.1491 CDS 1404106 1403612
-1 - 495 LPS-assembly CBSS- D23_1c1497 Neut_1428 lipoprotein RlpB
208964.1.peg.3988; precursor (Rare <br>Lipopolysaccharide
lipoprotein B) assembly fig|6666666.60966.peg.1492 CDS 1406732
1404126 -2 - 2607 Leucyl-tRNA synthetase CBSS- D23_1c1498 Neut_1429
(EC 6.1.1.4) 208964.1.peg.3988; <br>tRNA aminoacylation, Leu
fig|6666666.60966.peg.1493 CDS 1406756 1407925 2 + 1170 S- CBSS-
D23_1c1499 Neut_1430 adenosylmethionine:tRNA 211586.1.peg.2832;
ribosyltransferase- <br>Queuosine- isomerase (EC 5.--.--.--)
Archaeosine Biosynthesis; <br>Scaffold proteins for [4Fe--4S]
cluster assembly (MRP family); <br>tRNA modification Bacteria
fig|6666666.60966.peg.1494 CDS 1407922 1409007 1 + 1086
tRNA-guanine CBSS- D23_1c1500 Neut_1431 transglycosylase (EC
211586.1.peg.2832; 2.4.2.29) <br>Queuosine- Archaeosine
Biosynthesis; <br>Scaffold proteins for [4Fe--4S] cluster
assembly (MRP family); <br>tRNA modification Bacteria
fig|6666666.60966.peg.1495 CDS 1409072 1409536 2 + 465 Preprotein
translocase CBSS-211586.1.peg.2832 D23_1c1501 Neut_1432 subunit
YajC (TC 3.A.5.1.1) fig|6666666.60966.peg.1496 CDS 1409575 1411470
1 + 1896 Protein-export CBSS-211586.1.peg.2832 D23_1c1502 Neut_1433
membrane protein SecD (TC 3.A.5.1.1) fig|6666666.60966.peg.1497 CDS
1411495 1412427 1 + 933 Protein-export CBSS-211586.1.peg.2832
D23_1c1503 Neut_1434 membrane protein SecF (TC 3.A.5.1.1)
fig|6666666.60966.peg.1498 CDS 1412467 1412844 1 + 378 FIG028220:
-none- D23_1c1504 Neut_1435 hypothetical protein co- occurring with
HEAT repeat protein fig|6666666.60966.peg.1499 CDS 1412897 1413628
2 + 732 Ubiquinone/menaquinone Menaquinone and D23_1c1505 Neut_1436
biosynthesis Phylloquinone methyltransferase UbiE Biosynthesis; (EC
2.1.1.--) <br>Ubiquinone Biosynthesis; <br>Ubiquinone
Biosynthesis-gjo fig|6666666.60966.peg.1500 CDS 1413802 1413680 -1
- 123 Agmatinase (EC Arginine and Ornithine D23_1c1506 Neut_1437
3.5.3.11) Degradation; <br>Polyamine Metabolism
fig|6666666.60966.peg.1501 CDS 1414650 1413808 -3 - 843 Agmatinase
(EC Arginine and Ornithine D23_1c1507 Neut_1437 3.5.3.11)
Degradation; <br>Polyamine Metabolism
fig|6666666.60966.peg.1502 CDS 1415255 1414815 -2 - 441 Lipoprotein
signal Lipoprotein Biosynthesis; D23_1c1509 Neut_1438 peptidase (EC
3.4.23.36) <br>Signal peptidase fig|6666666.60966.peg.1503
CDS 1415346 1415224 -3 - 123 hypothetical protein -none- D23_1c1510
NA fig|6666666.60966.peg.1504 CDS 1418173 1415339 -1 - 2835
Isoleucyl-tRNA tRNA aminoacylation, Ile D23_1c1511 Neut_1439
synthetase (EC 6.1.1.5) fig|6666666.60966.peg.1505 CDS 1418945
1418148 -2 - 798 Riboflavin kinase (EC Riboflavin, FMN and FAD
D23_1c1512 Neut_1440 2.7.1.26)/FMN metabolism; adenylyltransferase
(EC <br>Riboflavin, FMN and 2.7.7.2) FAD metabolism;
<br>Riboflavin, FMN and FAD metabolism in plants;
<br>Riboflavin, FMN and FAD metabolism in plants;
<br>riboflavin to FAD; <br>riboflavin to FAD
fig|6666666.60966.peg.1506 CDS 1419539 1419237 -2 - 303 possible
sec- -none- D23_1c1513 Neut_1441 independent protein translocase
protein TatC fig|6666666.60966.peg.1507 CDS 1420011 1419886 -3 -
126 hypothetical protein -none- D23_1c1514 Neut_1442
fig|6666666.60966.peg.1508 CDS 1420112 1422079 2 + 1968
Dipeptide-binding ABC ABC transporter D23_1c1514 Neut_1442
transporter, periplasmic dipeptide (TC 3.A.1.5.2) substrate-binding
component (TC 3.A.1.5.2) fig|6666666.60966.peg.1509 CDS 1422089
1423066 2 + 978 Oligopeptide transport ABC transporter D23_1c1515
Neut_1443 system permease oligopeptide (TC protein OppB (TC
3.A.1.5.1) 3.A.1.5.1) fig|6666666.60966.peg.1511 CDS 1423196
1424851 2 + 1656 DnaJ-class molecular Protein chaperones D23_1c1516
Neut_1444 chaperone CbpA fig|6666666.60966.peg.1512 CDS 1424900
1425844 2 + 945 DnaJ-class molecular Protein chaperones D23_1c1517
Neut_1445 chaperone CbpA fig|6666666.60966.peg.1513 CDS 1425856
1426152 1 + 297 InterPro IPR000551 -none- D23_1c1518 Neut_1446
fig|6666666.60966.peg.1514 CDS 1426240 1427103 1 + 864 FIG00858431:
-none- D23_1c1519 Neut_1447 hypothetical protein
fig|6666666.60966.peg.1515 CDS 1427120 1427659 2 + 540 FAD
pyrophosphatase -none- D23_1c1520 Neut_1448 (EC 3.6.1.18),
projected from PMID:18815383 fig|6666666.60966.peg.1516 CDS 1428946
1428491 -1 - 456 Mobile element protein -none- D23_1c1522 Neut_2502
fig|6666666.60966.peg.1517 CDS 1429295 1428909 -2 - 387 Mobile
element protein -none- D23_1c1523 Neut_0884
fig|6666666.60966.peg.1518 CDS 1430487 1429300 -3 - 1188 Mobile
element protein -none- D23_1c1524 Neut_2405
fig|6666666.60966.peg.1519 CDS 1430505 1430621 3 + 117 patatin
family protein -none- D23_1c1525 Neut_1317
fig|6666666.60966.peg.1520 CDS 1430834 1430670 -2 - 165
hypothetical protein -none- D23_1c1526 NA
fig|6666666.60966.peg.1521 CDS 1431909 1431424 -3 - 486
hypothetical protein -none- D23_1c1527 Neut_1449
fig|6666666.60966.peg.1522 CDS 1432156 1431899 -1 - 258
hypothetical protein -none- D23_1c1528 Neut_1450
fig|6666666.60966.peg.1523 CDS 1432650 1432159 -3 - 492
phage-related -none- D23_1c1529 Neut_1451 hypothetical protein
fig|6666666.60966.peg.1524 CDS 1432970 1432650 -2 - 321
hypothetical protein -none- D23_1c1530 Neut_1452
fig|6666666.60966.peg.1525 CDS 1433143 1432967 -1 - 177
hypothetical protein -none- D23_1c1531 Neut_1453
fig|6666666.60966.peg.1526 CDS 1434487 1433552 -1 - 936
hypothetical protein -none- D23_1c1533 Neut_1454
fig|6666666.60966.peg.1527 CDS 1437226 1434497 -1 - 2730
hypothetical protein -none- D23_1c1534 Neut_1455
fig|6666666.60966.peg.1528 CDS 1437449 1437267 -2 - 183 Phage
protein -none- D23_1c1535 Neut_1456 fig|6666666.60966.peg.1529 CDS
1437694 1437467 -1 - 228 hypothetical protein -none- D23_1c1536
Neut_1457 fig|6666666.60966.peg.1530 CDS 1438472 1437702 -2 - 771
hypothetical protein -none- D23_1c1537 Neut_1458
fig|6666666.60966.peg.1531 CDS 1439638 1438469 -1 - 1170
hypothetical protein -none- D23_1c1538 Neut_1459
fig|6666666.60966.peg.1532 CDS 1441511 1439631 -2 - 1881 Phage tail
length tape- Phage tail proteins; D23_1c1539 Neut_1460 measure
protein <br>Phage tail proteins 2 fig|6666666.60966.peg.1533
CDS 1442755 1441508 -1 - 1248 Mobile element protein -none-
D23_1c1540 Neut_0357 fig|6666666.60966.peg.1534 CDS 1443390 1442854
-3 - 537 Phage protein -none- D23_1c1541 Neut_1460
fig|6666666.60966.peg.1535 CDS 1443638 1443390 -2 - 249
hypothetical protein -none- D23_1c1542 Neut_1461
fig|6666666.60966.peg.1536 CDS 1444027 1443677 -1 - 351 Phage
protein -none- D23_1c1543 Neut_1462 fig|6666666.60966.peg.1537 CDS
1444752 1444036 -3 - 717 major tail protein, -none- D23_1c1544
Neut_1463 putative fig|6666666.60966.peg.1538 CDS 1445120 1444758
-2 - 363 hypothetical protein -none- D23_1c1545 Neut_1464
fig|6666666.60966.peg.1539 CDS 1445638 1445117 -1 - 522
FIG00959132: -none- D23_1c1546 Neut_1465 hypothetical protein
fig|6666666.60966.peg.1540 CDS 1445985 1445650 -3 - 336 Phage
protein -none- D23_1c1547 Neut_1466 fig|6666666.60966.peg.1541 CDS
1446544 1445987 -1 - 558 Similar to Gene Transfer -none- D23_1c1548
Neut_1467 Agent (GTA) ORFG06 fig|6666666.60966.peg.1542 CDS 1446900
1446601 -3 - 300 hypothetical protein -none- D23_1c1549 Neut_1468
fig|6666666.60966.peg.1543 CDS 1448136 1446910 -3 - 1227 Phage
major capsid Phage capsid proteins D23_1c1550 Neut_1469 protein
fig|6666666.60966.peg.1544 CDS 1448949 1448218 -3 - 732 Prophage
Clp protease- cAMP signaling in D23_1c1551 Neut_1470 like protein
bacteria fig|6666666.60966.peg.1545 CDS 1450207 1448915 -1 - 1293
Phage portal protein Phage packaging D23_1c1552 Neut_1471 machinery
fig|6666666.60966.peg.1546 CDS 1451877 1450204 -3 - 1674 Phage
terminase large Phage packaging D23_1c1553 Neut_1472 subunit
machinery fig|6666666.60966.peg.1547 CDS 1452346 1451882 -1 - 465
Phage terminase, small Phage packaging D23_1c1554 Neut_1473 subunit
machinery fig|6666666.60966.peg.1548 CDS 1452801 1452478 -3 - 324
Phage holin -none- D23_1c1555 Neut_1474 fig|6666666.60966.peg.1549
CDS 1453267 1452887 -1 - 381 hypothetical protein -none- D23_1c1556
Neut_1475 fig|6666666.60966.peg.1550 CDS 1453430 1453269 -2 - 162
hypothetical protein -none- D23_1c1557 NA
fig|6666666.60966.peg.1551 CDS 1453630 1453451 -1 - 180
hypothetical protein -none- D23_1c1558 NA
fig|6666666.60966.peg.1552 CDS 1453862 1453623 -2 - 240
hypothetical protein -none- D23_1c1559 Neut_1477
fig|6666666.60966.peg.1553 CDS 1456504 1454171 -1 - 2334 DNA
primase, phage -none- D23_1c1560 Neut_1478 associated # P4-type
fig|6666666.60966.peg.1554 CDS 1456740 1456501 -3 - 240
hypothetical protein -none- D23_1c1561 NA
fig|6666666.60966.peg.1555 CDS 1456744 1456887 1 + 144
Phage-related protein -none- D23_1c1562 Neut_1480
fig|6666666.60966.peg.1556 CDS 1456894 1457172 1 + 279
Helix-turn-helix motif -none- D23_1c1563 Neut_1481
fig|6666666.60966.peg.1557 CDS 1457678 1457277 -2 - 402
hypothetical protein -none- D23_1c1564 NA
fig|6666666.60966.peg.1558 CDS 1458137 1458478 2 + 342 hypothetical
protein -none- D23_1c1565 NA fig|6666666.60966.peg.1559 CDS 1458868
1459158 1 + 291 hypothetical protein -none- D23_1c1566 NA
fig|6666666.60966.peg.1561 CDS 1459812 1459672 -3 - 141
hypothetical protein -none- D23_1c1567 NA
fig|6666666.60966.peg.1563 CDS 1460270 1460563 2 + 294 Mobile
element protein -none- D23_1c1568 Neut_1719
fig|6666666.60966.peg.1564 CDS 1460662 1461540 1 + 879 Mobile
element protein -none- D23_1c1569 Neut_1720
fig|6666666.60966.peg.1565 CDS 1462142 1461954 -2 - 189
hypothetical protein -none- D23_1c1570 Neut_1489
fig|6666666.60966.peg.1567 CDS 1462722 1462844 3 + 123 hypothetical
protein -none- D23_1c1571 NA fig|6666666.60966.peg.1568 CDS 1463137
1463829 1 + 693 putative nuclease -none- D23_1c1572 Neut_1491
fig|6666666.60966.peg.1569 CDS 1464806 1463826 -2 - 981 Abortive
infection -none- D23_1c1573 NA bacteriophage resistance protein
fig|6666666.60966.peg.1570 CDS 1466353 1465106 -1 - 1248 Mobile
element protein -none- D23_1c1574 Neut_0357
fig|6666666.60966.peg.1573 CDS 1466953 1467108 1 + 156 hypothetical
protein -none- D23_1c1575 NA fig|6666666.60966.peg.1574 CDS 1467105
1467389 3 + 285 hypothetical protein -none- D23_1c1576 Neut_1493
fig|6666666.60966.peg.1575 CDS 1467386 1467868 2 + 483 hypothetical
protein -none- D23_1c1577 Neut_1494 fig|6666666.60966.peg.1576 CDS
1467883 1468245 1 + 363 hypothetical protein -none- D23_1c1578
Neut_1495 fig|6666666.60966.peg.1577 CDS 1468255 1468638 1 + 384
hypothetical protein -none- D23_1c1579 Neut_1496
fig|6666666.60966.peg.1580 CDS 1469337 1470362 3 + 1026 Integrase
-none- D23_1c1580 Neut_1498 fig|6666666.60966.peg.1581 CDS 1470687
1470989 3 + 303 Exodeoxyribonuclease DNA repair, bacterial;
D23_1c1582 Neut_1499 VII small subunit (EC <br>Purine salvage
3.1.11.6) cluster fig|6666666.60966.peg.1582 CDS 1470979 1471872 1
+ 894 Octaprenyl diphosphate Isoprenoid Biosynthesis; D23_1c1583
Neut_1500 synthase (EC 2.5.1.90)/ <br>Isoprenoid
Dimethylallyltransferase Biosynthesis; (EC 2.5.1.1)/(2E,6E)-
<br>Isoprenoid farnesyl diphosphate Biosynthesis: synthase
(EC 2.5.1.10)/ Interconversions; Geranylgeranyl
<br>Isoprenoinds for diphosphate synthase Quinones; (EC
2.5.1.29) <br>Isoprenoinds for Quinones;
<br>Isoprenoinds for Quinones; <br>Isoprenoinds for
Quinones; <br>Polyprenyl Diphosphate Biosynthesis;
<br>Polyprenyl Diphosphate Biosynthesis; <br>Polyprenyl
Diphosphate Biosynthesis fig|6666666.60966.peg.1583 CDS 1471935
1473779 3 + 1845 1-deoxy-D-xylulose 5- Isoprenoid Biosynthesis;
D23_1c1584 Neut_1501 phosphate synthase (EC <br>Nonmevalonate
2.2.1.7) Branch of Isoprenoid Biosynthesis; <br>Pyridoxin
(Vitamin B6) Biosynthesis; <br>Thiamin biosynthesis
fig|6666666.60966.peg.1584 CDS 1473895 1474698 1 + 804 GTP
cyclohydrolase I Folate Biosynthesis; D23_1c1585 Neut_1502 (EC
3.5.4.16) type 2 <br>Queuosine- Archaeosine Biosynthesis;
<br>Zinc regulated enzymes fig|6666666.60966.peg.1585 CDS
1474865 1475485 2 + 621 InterPro IPR005134 -none- D23_1c1586
Neut_1503 COGs COG2862 fig|6666666.60966.peg.1586 CDS 1476254
1475514 -2 - 741 FolM Alternative Folate Biosynthesis D23_1c1587
Neut_1504 dihydrofolate reductase 1 fig|6666666.60966.peg.1587 CDS
1476327 1477502 3 + 1176 COG1565: -none- D23_1c1588 Neut_1505
Uncharacterized conserved protein fig|6666666.60966.peg.1588 CDS
1478242 1477499 -1 - 744 5'- Adenosyl nucleosidases; D23_1c1589
Neut_1506 methylthioadenosine <br>Adenosyl nucleosidase (EC
nucleosidases; 3.2.2.16)/S- <br>CBSS- adenosylhomocysteine
320388.3.peg.3759; nucleosidase (EC <br>CBSS- 3.2.2.9)
320388.3.peg.3759; <br>Methionine Biosynthesis;
<br>Methionine Degradation; <br>Polyamine Metabolism
fig|6666666.60966.peg.1589 CDS 1480269 1478239 -3 - 2031
Squalene--hopene CBSS- D23_1c1590 Neut_1507 cyclase (EC 5.4.99.17)
320388.3.peg.3759; <br>Hopanes fig|6666666.60966.peg.1590 CDS
1481103 1480384 -3 - 720 Surface lipoprotein -none- D23_1c1591
Neut_1508 fig|6666666.60966.peg.1591 CDS 1481997 1481389 -3 - 609
Ferric siderophore Ton and Tol transport D23_1c1592 Neut_1509
transport system, systems biopolymer transport protein ExbB
fig|6666666.60966.peg.1592 CDS 1482298 1483644 1 + 1347
Exodeoxyribonuclease DNA repair, bacterial; D23_1c1594 Neut_1510
VII large subunit (EC <br>Purine salvage 3.1.11.6) cluster
fig|6666666.60966.peg.1593 CDS 1483709 1484089 2 + 381 COG2363
-none- D23_1c1595 Neut_1511 fig|6666666.60966.peg.1594 CDS 1484150
1485328 2 + 1179 23S rRNA (guanine-N-2-)- RNA methylation
D23_1c1596 Neut_1512 methyltransferase rlmL EC 2.1.1.--)
fig|6666666.60966.peg.1595 CDS 1485345 1485833 3 + 489 Periplasmic
Biogenesis of c-type D23_1c1597 Neut_1513 thiol:disulfide
cytochromes; oxidoreductase DsbB, <br>Periplasmic disulfide
required for DsbA interchange reoxidation
fig|6666666.60966.peg.1596 CDS 1486114 1486503 1 + 390
Endoribonuclease L-PSP CBSS- D23_1c1598 Neut_1514
176299.4.peg.1996A fig|6666666.60966.peg.1598 CDS 1486998 1486651
-3 - 348 FIG016027: protein of -none- D23_1c1599 Neut_1515 unknown
function YeaO fig|6666666.60966.peg.1599 CDS 1487053 1487727 1 +
675 AttE component of AttEFGH ABC Transport D23_1c1600 Neut_1516
AttEFGH ABC transport System system fig|6666666.60966.peg.1600 CDS
1487724 1490273 3 + 2550 AttF component of AttEFGH ABC Transport
D23_1c1601 Neut_1517 AttEFGH ABC transport System;
<br>AttEFGH system/AttG ABC Transport System component of
AttEFGH ABC transport system fig|6666666.60966.peg.1601 CDS 1490273
1491343 2 + 1071 AttH component of AttEFGH ABC Transport D23_1c1602
Neut_1518 AttEFGH ABC transport System system
fig|6666666.60966.peg.1602 CDS 1491424 1491666 1 + 243
Molybdopterin -none- D23_1c1603 Neut_1519 biosynthesis protein B
fig|6666666.60966.peg.1603 CDS 1491738 1491619 -3 - 120
hypothetical protein -none- D23_1c1604 NA
fig|6666666.60966.peg.1605 CDS 1492158 1492982 3 + 825 Particulate
methane Particulate methane D23_1c1605 Neut_1520 monooxygenase C-
monooxygenase subunit (EC 1.14.13.25) (pMMO)
fig|6666666.60966.peg.1607 CDS 1494238 1493309 -1 - 930 Cytochrome
c551 Protection from Reactive D23_1c1607 Neut_1521 peroxidase (EC
1.11.1.5) Oxygen Species fig|6666666.60966.peg.1609 CDS 1494804
1495091 3 + 288 Mobile element protein -none- D23_1c1608 Neut_2502
fig|6666666.60966.peg.1611 CDS 1495989 1495288 -3 - 702
2-C-methyl-D-erythritol Isoprenoid Biosynthesis; D23_1c1609
Neut_1525 4-phosphate <br>Nonmevalonate cytidylyltransferase
(EC Branch of Isoprenoid
2.7.7.60) Biosynthesis; <br>Possible RNA degradation cluster;
<br>Stationary phase repair cluster
fig|6666666.60966.peg.1612 CDS 1496057 1496497 2 + 441 Inosine-5'-
Purine conversions; D23_1c1610 Neut_1526 monophosphate
<br>Purine salvage dehydrogenase (EC cluster 1.1.1.205)
fig|6666666.60966.peg.1613 CDS 1497472 1496552 -1 - 921 Cell
division protein Bacterial Cell Division; D23_1c1611 Neut_1527 FtsX
<br>Heat shock Cell division Proteases and a
Methyltransferase fig|6666666.60966.peg.1614 CDS 1498131 1497469 -3
- 663 Cell division Bacterial Cell Division; D23_1c1612 Neut_1528
transporter, ATP- <br>Heat shock Cell binding protein FtsE
(TC division Proteases and a 3.A.5.1.1) Methyltransferase
fig|6666666.60966.peg.1615 CDS 1499195 1498158 -2 - 1038 Signal
recognition Bacterial Cell Division; D23_1c1613 Neut_1529 particle
receptor <br>Bacterial signal protein FtsY (=alpha
recognition particle subunit) (TC 3.A.5.1.1) (SRP); <br>Heat
shock Cell division Proteases and a Methyltransferase;
<br>Universal GTPases fig|6666666.60966.peg.1616 CDS 1499262
1500653 3 + 1392 FIG015547: peptidase, -none- D23_1c1614 Neut_1530
M16 family fig|6666666.60966.peg.1617 CDS 1500780 1501865 3 + 1086
Alanine racemase (EC Alanine biosynthesis; D23_1c1615 Neut_1531
5.1.1.1) <br>Pyruvate Alanine Serine Interconversions
fig|6666666.60966.peg.1618 CDS 1502688 1501894 -3 - 795
Peptidyl-prolyl cis-trans Queuosine-Archaeosine D23_1c1616
Neut_1532 isomerase (EC 5.2.1.8) Biosynthesis
fig|6666666.60966.peg.1619 CDS 1502854 1502738 -1 - 117
hypothetical protein -none- D23_1c1617 NA
fig|6666666.60966.peg.1620 CDS 1503164 1502862 -2 - 303 YciL
protein Broadly distributed D23_1c1618 Neut_1533 proteins not in
subsystems; <br>CBSS- 211586.9.peg.2729
fig|6666666.60966.peg.1621 CDS 1504431 1503277 -3 - 1155
Rubredoxin-NAD(+) Rubrerythrin D23_1c1619 Neut_1534 reductase (EC
1.18.1.1) fig|6666666.60966.peg.1622 CDS 1504748 1505626 2 + 879
Probable protease htpX -none- D23_1c1620 Neut_1535 homolog (EC
3.4.24.--) fig|6666666.60966.peg.1623 CDS 1505626 1505739 1 + 114
hypothetical protein -none- D23_1c1621 NA
fig|6666666.60966.peg.1624 CDS 1506477 1505698 -3 - 780 Surface
lipoprotein -none- D23_1c1622 Neut_1536 fig|6666666.60966.peg.1625
CDS 1507909 1506626 -1 - 1284 Glutamate-1- CBSS-196164.1.peg.461;
D23_1c1623 Neut_1537 semialdehyde <br>Heme and Siroheme
aminotransferase (EC Biosynthesis 5.4.3.8)
fig|6666666.60966.peg.1626 CDS 1508584 1507946 -1 - 639
Thiamin-phosphate 5-FCL-like protein; D23_1c1624 Neut_1538
pyrophosphorylase (EC <br>Thiamin 2.5.1.3) biosynthesis
fig|6666666.60966.peg.1627 CDS 1509419 1508577 -2 - 843
Phosphomethylpyrimidine 5-FCL-like protein; D23_1c1625 Neut_1539
kinase (EC 2.7.4.7) <br>Thiamin biosynthesis
fig|6666666.60966.peg.1628 CDS 1509508 1509660 1 + 153 Rubredoxin
Rubrerythrin D23_1c1626 Neut_1540 fig|6666666.60966.peg.1629 CDS
1509660 1510049 3 + 390 Lactoylglutathione lyase Glutathione:
Non-redox D23_1c1627 Neut_1541 (EC 4.4.1.5) reactions;
<br>Methylglyoxal Metabolism fig|6666666.60966.peg.1630 CDS
1510238 1510603 2 + 366 probable iron binding -none- D23_1c1628
Neut_1542 protein from the HesB_IscA_SufA family
fig|6666666.60966.peg.1631 CDS 1511703 1510612 -3 - 1092 Anhydro-N-
Recycling of D23_1c1629 Neut_1543 acetylmuramic acid Peptidoglycan
Amino kinase (EC 2.7.1.--) Sugars fig|6666666.60966.peg.1632 CDS
1513070 1511739 -2 - 1332 Peptidase, M23/M37 -none- D23_1c1630
Neut_1544 family fig|6666666.60966.peg.1633 CDS 1513163 1514383 2 +
1221 Tyrosyl-tRNA tRNA aminoacylation, D23_1c1631 Neut_1545
synthetase (EC 6.1.1.1) Tyr fig|6666666.60966.peg.1634 CDS 1514577
1515674 3 + 1098 Myo-inositol 2- -none- D23_1c1632 Neut_1547
dehydrogenase (EC 1.1.1.18) fig|6666666.60966.peg.1635 CDS 1515687
1516748 3 + 1062 N-Acetylneuraminate CMP-N- D23_1c1633 Neut_1548
cytidylyltransferase (EC acetylneuraminate 2.7.7.43) Biosynthesis;
<br>Sialic Acid Metabolism fig|6666666.60966.peg.1636 CDS
1516926 1518425 3 + 1500 N-acetylneuraminate CMP-N- D23_1c1634
Neut_1549 synthase (EC 2.5.1.56) acetylneuraminate Biosynthesis;
<br>Sialic Acid Metabolism fig|6666666.60966.peg.1637 CDS
1518919 1518437 -1 - 483 Ribonucleotide Ribonucleotide D23_1c1635
Neut_1551 reductase redcution transcriptional regulator NrdR
fig|6666666.60966.peg.1638 CDS 1520246 1518996 -2 - 1251 Serine
5-FCL-like protein; D23_1c1636 Neut_1552 hydroxymethyltransferase
<br>Glycine (EC 2.1.2.1) Biosynthesis; <br>Glycine and
Serine Utilization; <br>Photorespiration (oxidative C2
cycle); <br>Serine Biosynthesis fig|6666666.60966.peg.1639
CDS 1520440 1521180 1 + 741 PqqC-like protein Folate Biosynthesis
D23_1c1638 Neut_1553 fig|6666666.60966.peg.1640 CDS 1522218 1521283
-3 - 936 Transcriptional LysR-family proteins in D23_1c1639
Neut_1554 activator MetR Escherichia coli; <br>LysR-family
proteins in Salmonella enterica Typhimurium; <br>Methionine
Biosynthesis fig|6666666.60966.peg.1641 CDS 1522318 1524594 1 +
2277 5- Methionine Biosynthesis D23_1c1640 Neut_1555
methyltetrahydropteroyltriglutamate-- homocysteine
methyltransferase (EC 2.1.1.14) fig|6666666.60966.peg.1643 CDS
1526020 1524767 -1 - 1254 UDP-N- Peptidoglycan D23_1c1641 Neut_1556
acetylglucosamine 1- Biosynthesis; <br>UDP-
carboxyvinyltransferase N-acetylmuramate from (EC 2.5.1.7)
Fructose-6-phosphate Biosynthesis fig|6666666.60966.peg.1644 CDS
1526108 1526497 2 + 390 Putative translation -none- D23_1c1642
Neut_1557 initiation inhibitor, yjgF family
fig|6666666.60966.peg.1645 CDS 1526528 1528585 2 + 2058
ATP-dependent DNA -none- D23_1c1643 Neut_1558 helicase RecG (EC
3.6.1.--) fig|6666666.60966.peg.1646 CDS 1529436 1528588 -3 - 849
Hypothetical ATP- -none- D23_1c1644 Neut_1559 binding protein
UPF0042, contains P- loop fig|6666666.60966.peg.1647 CDS 1529521
1530072 1 + 552 Transcription CBSS-243265.1.peg.198; D23_1c1645
Neut_1560 elongation factor GreB <br>Transcription factors
bacterial fig|6666666.60966.peg.1648 CDS 1532787 1530136 -3 - 2652
Malto-oligosyltrehalose -none- D23_1c1646 NA synthase (EC
5.4.99.15) fig|6666666.60966.peg.1649 CDS 1533038 1532850 -2 - 189
hypothetical protein -none- D23_1c1647 NA
fig|6666666.60966.peg.1650 CDS 1534716 1533031 -3 - 1686
Malto-oligosyltrehalose -none- D23_1c1648 Neut_1291
trehalohydrolase (EC 3.2.1.141) fig|6666666.60966.peg.1651 CDS
1535327 1534896 -2 - 432 Trehalose synthase, -none- D23_1c1649 NA
nucleoside diphosphate glucose dependent fig|6666666.60966.peg.1652
CDS 1535502 1535386 -3 - 117 hypothetical protein -none- D23_1c1650
NA fig|6666666.60966.peg.1653 CDS 1535501 1536028 2 + 528 Sensory
histidine kinase -none- D23_1c1651 Neut_1565 QseC
fig|6666666.60966.peg.1654 CDS 1535992 1536651 1 + 660 Sensory
histidine kinase -none- D23_1c1652 Neut_1565 QseC
fig|6666666.60966.peg.1655 CDS 1537148 1537849 2 + 702 Protein of
unknown -none- D23_1c1653 Neut_1566 function DUF484
fig|6666666.60966.peg.1656 CDS 1537833 1538798 3 + 966 Tyrosine
recombinase -none- D23_1c1654 Neut_1567 XerC
fig|6666666.60966.peg.1657 CDS 1539747 1538845 -3 - 903 Arogenate
Chorismate Synthesis; D23_1c1655 Neut_1568 dehydrogenase (EC
<br>Phenylalanine and 1.3.1.43) Tyrosine Branches from
Chorismate fig|6666666.60966.peg.1658 CDS 1540893 1539775 -3 - 1119
Biosynthetic Aromatic Phenylalanine and D23_1c1656 Neut_1569 amino
acid Tyrosine Branches from aminotransferase beta Chorismate (EC
2.6.1.57) fig|6666666.60966.peg.1659 CDS 1541973 1540915 -3 - 1059
Chorismate mutase I Chorismate Synthesis; D23_1c1657 Neut_1570 (EC
5.4.99.5)/ <br>Chorismate Prephenate Synthesis; dehydratase
(EC <br>Phenylalanine and 4.2.1.51) Tyrosine Branches from
Chorismate; <br>Phenylalanine and Tyrosine Branches from
Chorismate fig|6666666.60966.peg.1660 CDS 1543230 1542013 -3 - 1218
D-3-phosphoglycerate Glycine and Serine D23_1c1658 Neut_1571
dehydrogenase (EC Utilization; 1.1.1.95) <br>Pyridoxin
(Vitamin B6) Biosynthesis; <br>Serine Biosynthesis
fig|6666666.60966.peg.1661 CDS 1544329 1543223 -1 - 1107
Phosphoserine Glycine and Serine D23_1c1659 Neut_1572
aminotransferase (EC Utilization; 2.6.1.52) <br>Pyridoxin
(Vitamin B6) Biosynthesis; <br>Serine Biosynthesis
fig|6666666.60966.peg.1662 CDS 1546893 1544347 -3 - 2547 DNA gyrase
subunit A Cell Division Subsystem D23_1c1660 Neut_1573 (EC
5.99.1.3) including YidCD; <br>DNA gyrase subunits;
<br>DNA replication cluster 1; <br>DNA topoisomerases,
Type II, ATP-dependent; <br>Resistance to fluoroquinolones
fig|6666666.60966.peg.1663 CDS 1547556 1546963 -3 - 594 COGs
COG2854 -none- D23_1c1661 Neut_1574 fig|6666666.60966.peg.1664 CDS
1548691 1547573 -1 - 1119 Glycosyl transferase, -none- D23_1c1662
Neut_1575 family 2 fig|6666666.60966.peg.1665 CDS 1549918 1548755
-1 - 1164 Possible Fe--S -none- D23_1c1663 Neut_1576 oxidoreductase
fig|6666666.60966.peg.1666 CDS 1550134 1550247 1 + 114 hypothetical
protein -none- D23_1c1664 NA fig|6666666.60966.peg.1668 CDS 1550439
1552481 3 + 2043 Transketolase (EC Calvin-Benson cycle; D23_1c1666
Neut_1577 2.2.1.1) <br>Pentose phosphate pathway
fig|6666666.60966.peg.1669 CDS 1552544 1553551 2 + 1008
NADPH-dependent Calvin-Benson cycle; D23_1c1667 Neut_1578
glyceraldehyde-3- <br>Calvin-Benson cycle; phosphate
<br>Glycolysis and dehydrogenase (EC Gluconeogenesis;
1.2.1.13)/NAD- <br>Glycolysis and dependent Gluconeogenesis;
glyceraldehyde-3- <br>Pyridoxin (Vitamin phosphate B6)
Biosynthesis dehydrogenase (EC 1.2.1.12)
fig|6666666.60966.peg.1670 CDS 1553775 1553659 -3 - 117
hypothetical protein -none- D23_1c1668 NA
fig|6666666.60966.peg.1671 CDS 1553870 1555048 2 + 1179
Phosphoglycerate Calvin-Benson cycle; D23_1c1669 Neut_1579 kinase
(EC 2.7.2.3) <br>Glycolysis and Gluconeogenesis
fig|6666666.60966.peg.1672 CDS 1555083 1556573 3 + 1491 Pyruvate
kinase (EC Glycerate metabolism; D23_1c1670 Neut_1580 2.7.1.40)
<br>Glycolysis and Gluconeogenesis; <br>Pyruvate
metabolism I: anaplerotic reactions, PEP fig|6666666.60966.peg.1673
CDS 1556682 1557746 3 + 1065 Fructose-bisphosphate Calvin-Benson
cycle; D23_1c1671 Neut_1581 aldolase class II (EC
<br>Glycolysis and 4.1.2.13) Gluconeogenesis
fig|6666666.60966.peg.1674 CDS 1558432 1560090 1 + 1659 Cytochrome
c oxidases Terminal cytochrome C D23_1c1672 Neut_1582 subunit CcoN
(EC oxidases 1.9.3.1) fig|6666666.60966.peg.1675 CDS 1560080
1560688 2 + 609 Cytochrome c oxidase Terminal cytochrome C
D23_1c1673 Neut_1583 subunit CcoO (EC oxidases 1.9.3.1)
fig|6666666.60966.peg.1676 CDS 1560753 1561364 3 + 612
Copper-containing Denitrification; D23_1c1674 Neut_1584 nitrite
reductase (EC <br>Denitrifying 1.7.2.1) reductase gene
clusters fig|6666666.60966.peg.1677 CDS 1561404 1562054 3 + 651
Cytochrome oxidase Biogenesis of D23_1c1675 Neut_1585 biogenesis
protein cytochrome c oxidases Sco1/SenC/PrrC, putative copper
metallochaperone fig|6666666.60966.peg.1678 CDS 1562150 1562635 2 +
486 hypothetical -none- D23_1c1676 Neut_1586 cytochrome oxidase
associated membrane protein fig|6666666.60966.peg.1679 CDS 1563699
1562746 -3 - 954 Rare lipoprotein A Peptidoglycan D23_1c1677
Neut_1587 precursor Biosynthesis fig|6666666.60966.peg.1680 CDS
1564813 1563704 -1 - 1110 Rod shape-determining Bacterial
Cytoskeleton; D23_1c1678 Neut_1588 protein RodA <br>Bacterial
cell division cluster; <br>Peptidoglycan Biosynthesis
fig|6666666.60966.peg.1681 CDS 1566713 1564836 -2 - 1878
Penicillin-binding 16S rRNA modification D23_1c1679 Neut_1589
protein 2 (PBP-2) within P site of ribosome; <br>Bacterial
cell division cluster; <br>CBSS- 83331.1.peg.3039;
<br>Peptidoglycan Biosynthesis fig|6666666.60966.peg.1682 CDS
1567261 1566710 -1 - 552 Rod shape-determining Bacterial Cell
Division; D23_1c1680 Neut_1590 protein MreD <br>Bacterial
Cytoskeleton; <br>Bacterial cell division cluster;
<br>CBSS- 354.1.peg.2917 fig|6666666.60966.peg.1683 CDS
1568123 1567233 -2 - 891 Rod shape-determining Bacterial Cell
Division; D23_1c1681 Neut_1591 protein MreC <br>Bacterial
Cytoskeleton; <br>Bacterial cell division cluster;
<br>CBSS- 354.1.peg.2917 fig|6666666.60966.peg.1684 CDS
1569547 1568486 -1 - 1062 Rod shape-determining Bacterial Cell
Division; D23_1c1682 Neut_1592 protein MreB <br>Bacterial
Cytoskeleton; <br>Bacterial cell division cluster
fig|6666666.60966.peg.1685 CDS 1569665 1569997 2 + 333
Aspartyl-tRNA(Asn) tRNA aminoacylation, D23_1c1683 Neut_1593
amidotransferase Asp and Asn; <br>tRNA subunit C (EC 6.3.5.6)
@ aminoacylation, Glu and Glutamyl-tRNA(Gln) Gln amidotransferase
subunit C (EC 6.3.5.7) fig|6666666.60966.peg.1686 CDS 1570062
1571522 3 + 1461 Aspartyl-tRNA(Asn) tRNA aminoacylation, D23_1c1684
Neut_1594 amidotransferase Asp and Asn; <br>tRNA subunit A
(EC 6.3.5.6) @ aminoacylation, Glu and Glutamyl-tRNA(Gln) Gln
amidotransferase subunit A (EC 6.3.5.7) fig|6666666.60966.peg.1687
CDS 1571587 1573023 1 + 1437 Aspartyl-tRNA(Asn) tRNA
aminoacylation, D23_1c1685 Neut_1595 amidotransferase Asp and Asn;
<br>tRNA subunit B (EC 6.3.5.6) @ aminoacylation, Glu and
Glutamyl-tRNA(Gln) Gln amidotransferase subunit B (EC 6.3.5.7)
fig|6666666.60966.peg.1688 CDS 1573150 1573001 -1 - 150
hypothetical protein -none- D23_1c1686 NA
fig|6666666.60966.peg.1689 CDS 1573320 1573129 -3 - 192
FIG00859257: -none- D23_1c1687 NA hypothetical protein
fig|6666666.60966.peg.1691 CDS 1574140 1573703 -1 - 438 heat shock
protein, -none- D23_1c1688 Neut_1596 Hsp20 family
fig|6666666.60966.peg.1692 CDS 1574662 1574802 1 + 141 Integrase
-none- D23_1c1690 Neut_1498 fig|6666666.60966.peg.1693 CDS 1575055
1574942 -1 - 114 hypothetical protein -none- D23_1c1692 NA
fig|6666666.60966.peg.1694 CDS 1575572 1575369 -2 - 204
hypothetical protein -none- D23_1c1693 NA
fig|6666666.60966.peg.1696 CDS 1575911 1575753 -2 - 159 Mobile
element protein -none- D23_1c1694 Neut_1094
fig|6666666.60966.peg.1697 CDS 1576265 1578433 2 + 2169 GTP
pyrophosphokinase Stringent Response, D23_1c1695 Neut_1601 (EC
2.7.6.5), (p)ppGpp (p)ppGpp metabolism; synthetase II/
<br>Stringent Response, Guanosine- (p)ppGpp metabolism 3',5'-
bis(diphosphate) 3'- pyrophosphohydrolase (EC 3.1.7.2)
fig|6666666.60966.peg.1698 CDS 1578452 1579135 2 + 684 FIG00858669:
-none- D23_1c1696 Neut_1602 hypothetical protein
fig|6666666.60966.peg.1699 CDS 1579798 1579145 -1 - 654 Periplasmic
Biogenesis of c-type D23_1c1697 Neut_1603 thiol:disulfide
cytochromes; interchange protein <br>Periplasmic disulfide
DsbA interchange fig|6666666.60966.peg.1700 CDS 1580580 1579915 -3
- 666 Cell division protein -none- D23_1c1698 Neut_1604
fig|6666666.60966.peg.1701 CDS 1582304 1580604 -2 - 1701
Arginyl-tRNA synthetase tRNA aminoacylation, D23_1c1699 Neut_1605
(EC 6.1.1.19) Arg fig|6666666.60966.peg.1702 CDS 1582613 1583272 2
+ 660 FIG00859197: -none- D23_1c1700 Neut_1606 hypothetical protein
fig|6666666.60966.peg.1703 CDS 1583410 1584297 1 + 888
Methylenetetrahydrofolate 5-FCL-like protein; D23_1c1701 Neut_1607
dehydrogenase <br>One-carbon (NADP+) (EC 1.5.1.5)/ metabolism
by Methenyltetrahydrofolate tetrahydropterines; cyclohydrolase (EC
<br>One-carbon 3.5.4.9) metabolism by tetrahydropterines
fig|6666666.60966.peg.1704 CDS 1584339 1586999 3 + 2661 Pyruvate
5-FCL-like protein; D23_1c1702 Neut_1608 dehydrogenase E1
<br>Dehydrogenase component (EC 1.2.4.1) complexes;
<br>Methionine Degradation; <br>Pyruvate metabolism II:
acetyl- CoA, acetogenesis from pyruvate fig|6666666.60966.peg.1705
CDS 1587072 1588421 3 + 1350 Dihydrolipoamide 5-FCL-like protein;
D23_1c1703 Neut_1609 acetyltransferase <br>Dehydrogenase
component of pyruvate complexes; dehydrogenase <br>Pyruvate
complex (EC 2.3.1.12) metabolism II: acetyl- CoA, acetogenesis from
pyruvate fig|6666666.60966.peg.1706 CDS 1588457 1589170 2 + 714
Nicotinate-nucleotide NAD and NADP cofactor D23_1c1704 Neut_1610
adenylyltransferase (EC biosynthesis global 2.7.7.18)
fig|6666666.60966.peg.1707 CDS 1589167 1589532 1 + 366 Iojap
protein -none- D23_1c1705 Neut_1611 fig|6666666.60966.peg.1708 CDS
1589624 1590091 2 + 468 LSU m3Psi1915 RNA methylation; D23_1c1706
Neut_1612 methyltransferase RlmH <br>Ribosome biogenesis
bacterial; <br>tRNA modification Bacteria
fig|6666666.60966.peg.1709 CDS 1590169 1590792 1 + 624 Septum
formation Bacterial Cell Division; D23_1c1707 Neut_1613 protein Maf
<br>Bacterial Cytoskeleton; <br>Bacterial cell division
cluster; <br>CBSS- 354.1.peg.2917 fig|6666666.60966.peg.1710
CDS 1590825 1592276 3 + 1452 Cytoplasmic axial Bacterial Cell
Division; D23_1c1708 Neut_1614 filament protein CafA
<br>CBSS- and Ribonuclease G (EC 354.1.peg.2917; 3.1.4.--)
<br>RNA processing and degradation, bacterial
fig|6666666.60966.peg.1711 CDS 1592500 1593222 1 + 723 Ferric
siderophore Ton and Tol transport D23_1c1709 Neut_1615 transport
system, systems periplasmic binding protein TonB
fig|6666666.60966.peg.1712 CDS 1593226 1594023 1 + 798
MotA/TolQ/ExbB Ton and Tol transport D23_1c1710 Neut_1616 proton
channel family systems protein fig|6666666.60966.peg.1713 CDS
1594023 1594448 3 + 426 Biopolymer transport Ton and Tol transport
D23_1c1711 Neut_1617 protein ExbD/TolR systems
fig|6666666.60966.peg.1714 CDS 1595300 1594518 -2 - 783 23S rRNA
(guanosine- RNA methylation D23_1c1712 Neut_1618 2'-O-)-
methyltransferase rlmB (EC 2.1.1.--) fig|6666666.60966.peg.1715 CDS
1597532 1595328 -2 - 2205 3'-to-5' RNA processing and D23_1c1713
Neut_1619 exoribonuclease RNase R degradation, bacterial
fig|6666666.60966.peg.1717 CDS 1598152 1599303 1 + 1152 DNA
polymerase IV (EC DNA repair, bacterial D23_1c1715 Neut_1620
2.7.7.7) fig|6666666.60966.peg.1718 CDS 1599507 1599391 -3 - 117
hypothetical protein -none- D23_1c1716 NA
fig|6666666.60966.peg.1719 CDS 1599639 1601015 3 + 1377 Flagellar
regulatory Flagellum D23_1c1717 Neut_1621 protein FleQ
fig|6666666.60966.peg.1720 CDS 1601809 1601045 -1 - 765
hypothetical protein -none- D23_1c1718 Neut_1622
fig|6666666.60966.peg.1721 CDS 1604085 1601893 -3 - 2193
hypothetical protein -none- D23_1c1719 Neut_1623
fig|6666666.60966.peg.1722 CDS 1605035 1604157 -2 - 879 Mobile
element protein -none- D23_1c1720 Neut_1720
fig|6666666.60966.peg.1723 CDS 1605427 1605134 -1 - 294 Mobile
element protein -none- D23_1c1721 Neut_1719
fig|6666666.60966.peg.1724 CDS 1606591 1605455 -1 - 1137 8-amino-7-
Biotin biosynthesis; D23_1c1722 Neut_2137 oxononanoate synthase
<br>Biotin biosynthesis (EC 2.3.1.47) Experimental;
<br>Biotin synthesis cluster fig|6666666.60966.peg.1725 CDS
1608741 1606597 -3 - 2145 hypothetical protein -none- D23_1c1723 NA
fig|6666666.60966.peg.1726 CDS 1610072 1608738 -2 - 1335
hypothetical protein -none- D23_1c1724 NA
fig|6666666.60966.peg.1727 CDS 1610798 1610106 -2 - 693
hypothetical protein -none- D23_1c1725 Neut_1626
fig|6666666.60966.peg.1728 CDS 1611531 1610833 -3 - 699
hypothetical protein -none- D23_1c1726 Neut_1626
fig|6666666.60966.peg.1729 CDS 1611922 1612056 1 + 135 hypothetical
protein -none- D23_1c1727 NA fig|6666666.60966.peg.1731 CDS 1612368
1612991 3 + 624 InterPro IPR000379 -none- D23_1c1729 Neut_1627 COGs
COG2945 fig|6666666.60966.peg.1732 CDS 1614001 1613204 -1 - 798
Carbonic anhydrase
(EC Zinc regulated enzymes D23_1c1730 Neut_1628 4.2.1.1)
fig|6666666.60966.peg.1734 CDS 1614522 1614355 -3 - 168
hypothetical protein -none- D23_1c1731 NA
fig|6666666.60966.peg.1735 CDS 1614827 1614699 -2 - 129
hypothetical protein -none- D23_1c1732 NA
fig|6666666.60966.peg.1736 CDS 1614794 1616134 2 + 1341 Probable
-none- D23_1c1733 Neut_1630 transmembrane protein
fig|6666666.60966.peg.1737 CDS 1617043 1616225 -1 - 819 rRNA
methylases -none- D23_1c1734 Neut_1631 fig|6666666.60966.peg.1738
CDS 1617516 1617061 -3 - 456 Mobile element protein -none-
D23_1c1735 Neut_2502 fig|6666666.60966.peg.1739 CDS 1617913 1617479
-1 - 435 Mobile element protein -none- D23_1c1736 Neut_0884
fig|6666666.60966.peg.1740 CDS 1618427 1618293 -2 - 135
hypothetical protein -none- D23_1c1738 NA
fig|6666666.60966.peg.1741 CDS 1619838 1618420 -3 - 1419
Dihydrolipoamide 5-FCL-like protein; D23_1c1739 Neut_1632
dehydrogenase (EC <br>Glycine cleavage 1.8.1.4) system;
<br>Photorespiration (oxidative C2 cycle); <br>TCA
Cycle fig|6666666.60966.peg.1742 CDS 1620067 1621053 1 + 987 Malate
dehydrogenase TCA Cycle D23_1c1740 Neut_1633 (EC 1.1.1.37)
fig|6666666.60966.peg.1743 CDS 1621562 1621107 -2 - 456 Thiol
peroxidase, Bcp- CBSS- D23_1c1741 Neut_1634 type (EC 1.11.1.15)
316057.3.peg.3521; <br>Thioredoxin- disulfide reductase
fig|6666666.60966.peg.1744 CDS 1622938 1621595 -1 - 1344 Cytochrome
c heme Biogenesis of c-type D23_1c1742 Neut_1635 lyase subunit CcmH
cytochromes; <br>Copper homeostasis
fig|6666666.60966.peg.1745 CDS 1623399 1622935 -3 - 465 Cytochrome
c heme Biogenesis of c-type D23_1c1743 Neut_1636 lyase subunit CcmL
cytochromes fig|6666666.60966.peg.1746 CDS 1623982 1623458 -1 - 525
Cytochrome c-type Biogenesis of c-type D23_1c1744 Neut_1637
biogenesis protein cytochromes; CcmG/DsbE, <br>Periplasmic
disulfide thiol:disulfide interchange oxidoreductase
fig|6666666.60966.peg.1747 CDS 1626024 1623979 -3 - 2046 Cytochrome
c heme Biogenesis of c-type D23_1c1745 Neut_1638 lyase subunit CcmF
cytochromes; <br>Copper homeostasis
fig|6666666.60966.peg.1748 CDS 1626514 1626065 -1 - 450 Cytochrome
c-type Biogenesis of c-type D23_1c1746 Neut_1639 biogenesis protein
cytochromes CcmE, heme chaperone fig|6666666.60966.peg.1749 CDS
1627373 1626690 -2 - 684 Cytochrome c-type Biogenesis of c-type
D23_1c1747 Neut_1641 biogenesis protein cytochromes CcmC, putative
heme lyase for CcmE fig|6666666.60966.peg.1750 CDS 1628195 1627536
-2 - 660 ABC transporter Biogenesis of c-type D23_1c1748 Neut_1642
involved in cytochrome cytochromes c biogenesis, CcmB subunit
fig|6666666.60966.peg.1751 CDS 1628729 1628202 -2 - 528 ABC
transporter Biogenesis of c-type D23_1c1749 Neut_1643 involved in
cytochrome cytochromes c biogenesis, ATPase component CcmA
fig|6666666.60966.peg.1752 CDS 1629793 1628927 -1 - 867 tRNA
pseudouridine CBSS- D23_1c1750 Neut_1644 synthase B (EC 4.2.1.70)
138119.3.peg.2719; <br>RNA pseudouridine syntheses;
<br>Riboflavin, FMN and FAD metabolism in plants;
<br>tRNA modification Bacteria; <br>tRNA processing
fig|6666666.60966.peg.1753 CDS 1630354 1630001 -1 - 354
Ribosome-binding CBSS- D23_1c1751 Neut_1645 factor A
138119.3.peg.2719; <br>NusA-TFII Cluster;
<br>Translation initiation factors bacterial
fig|6666666.60966.peg.1754 CDS 1633073 1630407 -2 - 2667
Translation initiation CBSS- D23_1c1752 Neut_1646 factor 2
138119.3.peg.2719; <br>NusA-TFII Cluster;
<br>Translation initiation factors bacterial;
<br>Universal GTPases fig|6666666.60966.peg.1756 CDS 1634664
1633192 -3 - 1473 Transcription NusA-TFII Cluster; D23_1c1753
Neut_1647 termination protein <br>Transcription NusA factors
bacterial fig|6666666.60966.peg.1757 CDS 1635199 1634717 -1 - 483
COG0779: clustered -none- D23_1c1754 Neut_1648 with transcription
termination protein NusA fig|6666666.60966.peg.1760 CDS 1636174
1636611 1 + 438 FIG00859331: -none- D23_1c1755 Neut_1650
hypothetical protein fig|6666666.60966.peg.1761 CDS 1637012 1636686
-2 - 327 Cytochrome c4 Soluble cytochromes D23_1c1756 Neut_1651 and
functionally related electron carriers fig|6666666.60966.peg.1762
CDS 1637371 1637045 -1 - 327 Putative periplasmic -none- D23_1c1757
Neut_1652 cytochrome type-C oxidoreductase signal peptide protein
(EC 1.--.--.--) fig|6666666.60966.peg.1763 CDS 1639430 1637484 -2 -
1947 COG0488: ATPase -none- D23_1c1758 Neut_1653 components of ABC
transporters with duplicated ATPase domains
fig|6666666.60966.peg.1765 CDS 1639660 1640709 1 + 1050 Selenide,
water dikinase Selenocysteine D23_1c1759 Neut_1654 (EC 2.7.9.3)
metabolism; <br>tRNA modification Bacteria
fig|6666666.60966.peg.1766 CDS 1640702 1641868 2 + 1167
Selenophosphate- Selenocysteine D23_1c1760 Neut_1655 dependent tRNA
2- metabolism; <br>tRNA selenouridine synthase modification
Bacteria fig|6666666.60966.peg.1767 CDS 1642217 1642050 -2 - 168
hypothetical protein -none- D23_1c1761 NA
fig|6666666.60966.peg.1768 CDS 1643785 1642217 -1 - 1569 4-cresol
dehydrogenase Cresol degradation D23_1c1762 Neut_1656
[hydroxylating] flavoprotein subunit (EC 1.17.99.1)
fig|6666666.60966.peg.1769 CDS 1644507 1643782 -3 - 726 PchX
protein -none- D23_1c1763 Neut_1657 fig|6666666.60966.peg.1770 CDS
1644874 1644518 -1 - 357 4-cresol dehydrogenase Cresol degradation
D23_1c1764 Neut_1658 [hydroxylating] cytochrome c subunit precursor
fig|6666666.60966.peg.1771 CDS 1646175 1645138 -3 - 1038
Dihydroorotase (EC De Novo Pyrimidine D23_1c1766 Neut_1659 3.5.2.3)
Synthesis; <br>Zinc regulated enzymes
fig|6666666.60966.peg.1772 CDS 1647130 1646273 -1 - 858 rRNA small
subunit 16S rRNA modification D23_1c1767 Neut_1660
methyltransferase I within P site of ribosome; <br>CBSS-
160492.1.peg.550; <br>Heat shock dnaK gene cluster extended
fig|6666666.60966.peg.1773 CDS 1647311 1649101 2 + 1791 ABC
transporter, -none- D23_1c1769 Neut_1661 multidrug efflux family
fig|6666666.60966.peg.1774 CDS 1649206 1649556 1 + 351 Predicted
endonuclease CBSS-160492.1.peg.550 D23_1c1770 Neut_1662 distantly
related to archaeal Holliday junction resolvase
fig|6666666.60966.peg.1776 CDS 1651143 1649929 -3 - 1215
hypothetical protein -none- D23_1c1771 Neut_1663
fig|6666666.60966.peg.1777 CDS 1651568 1651446 -2 - 123
hypothetical protein -none- D23_1c1772 NA
fig|6666666.60966.peg.1778 CDS 1651714 1652223 1 + 510 Putative
lipoprotein -none- D23_1c1773 Neut_1664 fig|6666666.60966.peg.1779
CDS 1652740 1661706 1 + 8967 Cyclic beta-1,2-glucan Synthesis of
D23_1c1774 Neut_1665 synthase (EC 2.4.1.--) osmoregulated
periplasmic glucans fig|6666666.60966.peg.1780 CDS 1662138 1661821
-3 - 318 Mobile element protein -none- D23_1c1775 Neut_1666
fig|6666666.60966.peg.1781 CDS 1662168 1662344 3 + 177 hypothetical
protein -none- D23_1c1776 NA fig|6666666.60966.peg.1782 CDS 1662546
1662406 -3 - 141 Mobile element protein -none- D23_1c1777 Neut_2190
fig|6666666.60966.peg.1783 CDS 1663286 1663158 -2 - 129
hypothetical protein -none- D23_1c1778 NA
fig|6666666.60966.peg.1784 CDS 1663556 1664518 2 + 963 Mobile
element protein -none- D23_1c1779 Neut_1746
fig|6666666.60966.peg.1785 CDS 1666051 1664585 -1 - 1467
ATP-dependent RNA ATP-dependent RNA D23_1c1780 Neut_1668 helicase
helicases, bacterial Bcep18194_A5658 fig|6666666.60966.peg.1786 CDS
1666377 1666147 -3 - 231 Mobile element protein -none- D23_1c1781
Neut_2088 fig|6666666.60966.peg.1787 CDS 1666620 1666441 -3 - 180
Mobile element protein -none- D23_1c1782 Neut_0332
fig|6666666.60966.peg.1788 CDS 1667117 1666644 -2 - 474 Mobile
element protein -none- D23_1c1783 NA fig|6666666.60966.peg.1789 CDS
1668091 1667294 -1 - 798 FIG00861229: -none- D23_1c1784 Neut_1669
hypothetical protein fig|6666666.60966.peg.1790 CDS 1668254 1668093
-2 - 162 hypothetical protein -none- D23_1c1785 NA
fig|6666666.60966.peg.1791 CDS 1669037 1668330 -2 - 708 Cytochrome
c family -none- D23_1c1786 Neut_2333 protein
fig|6666666.60966.peg.1792 CDS 1670220 1669099 -3 - 1122
FIG00859557: -none- D23_1c1787 Neut_1792 hypothetical protein
fig|6666666.60966.peg.1793 CDS 1671929 1670217 -2 - 1713
Hydroxylamine -none- D23_1c1788 Neut_2335 oxidoreductase precursor
(EC 1.7.3.4) fig|6666666.60966.peg.1794 CDS 1672280 1672017 -2 -
264 SSU ribosomal protein -none- D23_1c1789 NA S20p
fig|6666666.60966.peg.1795 CDS 1672473 1672634 3 + 162 hypothetical
protein -none- D23_1c1790 NA fig|6666666.60966.peg.1796 CDS 1672870
1672601 -1 - 270 Mobile element protein -none- D23_1c1791 Neut_2450
fig|6666666.60966.peg.1797 CDS 1673187 1672894 -3 - 294
hypothetical protein -none- D23_1c1792 Neut_2449
fig|6666666.60966.peg.1798 CDS 1673875 1673648 -1 - 228
hypothetical protein -none- D23_1c1795 Neut_1676
fig|6666666.60966.peg.1799 CDS 1674438 1674052 -3 - 387 FIG002082:
Protein A Gammaproteobacteria D23_1c1796 Neut_1677 SirB2 Cluster
Relating to Translation fig|6666666.60966.peg.1800 CDS 1674844
1674500 -1 - 345 FIG00858740: -none- D23_1c1797 Neut_1678
hypothetical protein fig|6666666.60966.peg.1801 CDS 1675595 1674939
-2 - 657 Probable membrane -none- D23_1c1798 Neut_1679 protein
fig|6666666.60966.peg.1802 CDS 1675804 1675601 -1 - 204 Probable
membrane -none- D23_1c1800 Neut_1679 protein
fig|6666666.60966.peg.1803 CDS 1676931 1675825 -3 - 1107 GbcA
Glycine betaine -none- D23_1c1801 Neut_1680 demethylase subunit A
fig|6666666.60966.peg.1804 CDS 1677301 1678686 1 + 1386
FIG00858667: -none- D23_1c1802 Neut_1681 hypothetical protein
fig|6666666.60966.peg.1805 CDS 1678742 1680964 2 + 2223 Helicase
PriA essential -none- D23_1c1803 Neut_1682 for oriC/DnaA-
independent DNA replication fig|6666666.60966.peg.1806 CDS 1681478
1681032 -2 - 447 Universal stress protein -none- D23_1c1804
Neut_1683 fig|6666666.60966.peg.1807 CDS 1683246 1681597 -3 - 1650
Folate transporter 3 -none- D23_1c1805 Neut_1684
fig|6666666.60966.peg.1808 CDS 1684397 1683258 -2 - 1140 Outer
membrane stress Periplasmic Stress D23_1c1806 Neut_1685 sensor
protease DegS Response; <br>Proteolysis in bacteria,
ATP-dependent fig|6666666.60966.peg.1809 CDS 1684396 1685181 1 +
786 FIG137478: -none-
D23_1c1807 Neut_1686 Hypothetical protein YbgI
fig|6666666.60966.peg.1810 CDS 1685374 1685249 -1 - 126
hypothetical protein -none- D23_1c1808 NA
fig|6666666.60966.peg.1811 CDS 1685328 1686644 3 + 1317
Membrane-bound lytic Murein Hydrolases D23_1c1809 Neut_1687 murein
transglycosylase A precursor (EC 3.2.1.--)
fig|6666666.60966.peg.1812 CDS 1687397 1686684 -2 - 714
Thiol:disulfide Periplasmic disulfide D23_1c1810 Neut_1688
interchange protein interchange DsbC fig|6666666.60966.peg.1813 CDS
1688609 1687443 -2 - 1167 2-octaprenyl-3-methyl-
CBSS-87626.3.peg.3639; D23_1c1811 Neut_1689 6-methoxy-1,4-
<br>Ubiquinone benzoquinol Biosynthesis; hydroxylase (EC
<br>Ubiquinone 1.14.13.--) Biosynthesis-gjo
fig|6666666.60966.peg.1814 CDS 1688840 1690807 2 + 1968
Acetyl-coenzyme A Pyruvate metabolism II: D23_1c1812 Neut_1690
synthetase (EC 6.2.1.1) acetyl-CoA, acetogenesis from pyruvate
fig|6666666.60966.peg.1815 CDS 1690825 1691799 1 + 975
Beta-lactamase related -none- D23_1c1813 Neut_1691 protein
fig|6666666.60966.peg.1816 CDS 1693183 1691903 -1 - 1281
amidohydrolase -none- D23_1c1814 Neut_1692
fig|6666666.60966.peg.1817 CDS 1693463 1693633 2 + 171 Mobile
element protein -none- D23_1c1816 Neut_1693
fig|6666666.60966.peg.1818 CDS 1694024 1695034 2 + 1011 Fatty acid
desaturase -none- D23_1c1817 Neut_1694 fig|6666666.60966.peg.1819
CDS 1696649 1695402 -2 - 1248 Mobile element protein -none-
D23_1c1818 Neut_0357 fig|6666666.60966.peg.1820 CDS 1697303 1696830
-2 - 474 Mobile element protein -none- D23_1c1820 Neut_1256
fig|6666666.60966.peg.1821 CDS 1697769 1697377 -3 - 393
hypothetical protein -none- D23_1c1821 Neut_2449
fig|6666666.60966.peg.1822 CDS 1698235 1698032 -1 - 204
hypothetical protein -none- D23_1c1822 Neut_0363
fig|6666666.60966.peg.1823 CDS 1698639 1698322 -3 - 318
hypothetical protein -none- D23_1c1823 Neut_1695
fig|6666666.60966.peg.1824 CDS 1698977 1698639 -2 - 339 Mobile
element protein -none- D23_1c1824 Neut_1696
fig|6666666.60966.peg.1825 CDS 1699393 1702311 1 + 2919 Na(+) H(+)
antiporter Multi-subunit cation D23_1c1825 Neut_1697 subunit
A/Na(+) H(+) antiporter; <br>Multi- antiporter subunit B
subunit cation antiporter fig|6666666.60966.peg.1826 CDS 1702311
1702655 3 + 345 Na(+) H(+) antiporter Multi-subunit cation
D23_1c1826 Neut_1698 subunit C antiporter
fig|6666666.60966.peg.1827 CDS 1702652 1704298 2 + 1647 Na(+) H(+)
antiporter Multi-subunit cation D23_1c1827 Neut_1699 subunit D
antiporter fig|6666666.60966.peg.1828 CDS 1704295 1704780 1 + 486
Na(+) H(+) antiporter Multi-subunit cation D23_1c1828 Neut_1700
subunit E antiporter fig|6666666.60966.peg.1829 CDS 1704777 1705058
3 + 282 Na(+) H(+) antiporter Multi-subunit cation D23_1c1829
Neut_1701 subunit F antiporter fig|6666666.60966.peg.1830 CDS
1705055 1705480 2 + 426 Na(+) H(+) antiporter Multi-subunit cation
D23_1c1830 Neut_1702 subunit G antiporter
fig|6666666.60966.peg.1831 CDS 1708136 1705638 -2 - 2499
FIG00809136: -none- D23_1c1831 Neut_1703 hypothetical protein
fig|6666666.60966.peg.1832 CDS 1709066 1708266 -2 - 801 ABC
transporter ATP- -none- D23_1c1832 Neut_1704 binding protein YvcR
fig|6666666.60966.peg.1833 CDS 1709065 1709676 1 + 612 Arylesterase
precursor -none- D23_1c1833 Neut_1705 (EC 3.1.1.2)
fig|6666666.60966.peg.1834 CDS 1710780 1709716 -3 - 1065 Ribosomal
large subunit RNA pseudouridine D23_1c1834 Neut_1706 pseudouridine
synthase syntheses; C (EC 4.2.1.70) <br>Ribosome biogenesis
bacterial fig|6666666.60966.peg.1835 CDS 1711189 1713738 1 + 2550
Ribonuclease E (EC RNA processing and D23_1c1835 Neut_1707
3.1.26.12) degradation, bacterial; <br>Ribosome biogenesis
bacterial fig|6666666.60966.peg.1836 CDS 1714787 1713870 -2 - 918
Tyrosine recombinase -none- D23_1c1836 Neut_1708 XerD
fig|6666666.60966.peg.1837 CDS 1715754 1714909 -3 - 846
CcsA-related protein -none- D23_1c1837 Neut_1709
fig|6666666.60966.peg.1838 CDS 1715897 1717246 2 + 1350 Signal
recognition Bacterial signal D23_1c1838 Neut_1710 particle, subunit
Ffh recognition particle SRP54 (TC 3.A.5.1.1) (SRP);
<br>Universal GTPases fig|6666666.60966.peg.1839 CDS 1717562
1718059 2 + 498 Cytosine/adenosine -none- D23_1c1840 Neut_1711
deaminases fig|6666666.60966.peg.1840 CDS 1719089 1718079 -2 - 1011
collagen triple helix -none- D23_1c1841 Neut_1712 repeat domain
protein fig|6666666.60966.peg.1841 CDS 1719941 1719435 -2 - 507
Mobile element protein -none- D23_1c1843 Neut_1353
fig|6666666.60966.peg.1843 CDS 1720927 1720256 -1 - 672 Putative
TEGT family CBSS-326442.4.peg.1852 D23_1c1844 Neut_1715
carrier/transport protein fig|6666666.60966.peg.1844 CDS 1721245
1721081 -1 - 165 hypothetical protein -none- D23_1c1845 Neut_1716
fig|6666666.60966.peg.1845 CDS 1721933 1721268 -2 - 666 Mobile
element protein -none- D23_1c1846 Neut_1717
fig|6666666.60966.peg.1846 CDS 1722745 1722137 -1 - 609 Aldehyde
Glycerolipid and D23_1c1847 Neut_0700 dehydrogenase (EC
Glycerophospholipid 1.2.1.3) Metabolism in Bacteria;
<br>Methylglyoxal Metabolism; <br>Methylglyoxal
Metabolism; <br>Pyruvate metabolism II: acetyl- CoA,
acetogenesis from pyruvate fig|6666666.60966.peg.1847 CDS 1722896
1723189 2 + 294 Mobile element protein -none- D23_1c1848 Neut_1719
fig|6666666.60966.peg.1848 CDS 1723288 1724166 1 + 879 Mobile
element protein -none- D23_1c1849 Neut_1720
fig|6666666.60966.peg.1849 CDS 1724724 1724179 -3 - 546 Aldehyde
Glycerolipid and D23_1c1850 Neut_0700 dehydrogenase (EC
Glycerophospholipid 1.2.1.3) Metabolism in Bacteria;
<br>Methylglyoxal Metabolism; <br>Methylglyoxal
Metabolism; <br>Pyruvate metabolism II: acetyl- CoA,
acetogenesis from pyruvate fig|6666666.60966.peg.1850 CDS 1726242
1724995 -3 - 1248 Mobile element protein -none- D23_1c1851
Neut_0357 fig|6666666.60966.peg.1851 CDS 1727368 1727126 -1 - 243
Mobile element protein -none- D23_1c1854 Neut_2190
fig|6666666.60966.peg.1852 CDS 1727480 1727641 2 + 162 hypothetical
protein -none- D23_1c1855 NA fig|6666666.60966.peg.1853 CDS 1727757
1727873 3 + 117 hypothetical protein -none- D23_1c1856 NA
fig|6666666.60966.peg.1854 CDS 1727880 1728818 3 + 939 Major
facilitator family -none- D23_1c1857 NA transporter
fig|6666666.60966.peg.1855 CDS 1728936 1730123 3 + 1188 Cytosine
deaminase (EC CBSS- D23_1c1858 Neut_1722 3.5.4.1)
326442.4.peg.1852; <br>Creatine and Creatinine Degradation;
<br>pyrimidine conversions fig|6666666.60966.peg.1857 CDS
1730427 1730624 3 + 198 Mobile element protein -none- D23_1c1859
Neut_1748 fig|6666666.60966.peg.1858 CDS 1730716 1730937 1 + 222
Mobile element protein -none- D23_1c1860 Neut_1747
fig|6666666.60966.peg.1859 CDS 1731165 1733414 3 + 2250 Lead,
cadmium, zinc Copper Transport D23_1c1862 Neut_1724 and mercury
System; <br>Copper transporting ATPase (EC homeostasis
3.6.3.3) (EC 3.6.3.5); Copper-translocating P- type ATPase (EC
3.6.3.4) fig|6666666.60966.peg.1860 CDS 1733755 1733946 1 + 192
hypothetical protein -none- D23_1c1863 Neut_1734
fig|6666666.60966.peg.1861 CDS 1734020 1735762 2 + 1743 Asparagine
synthetase Cyanophycin D23_1c1864 Neut_1735 [glutamine-hydrolyzing]
Metabolism; (EC 6.3.5.4) <br>Glutamate and Aspartate uptake
in Bacteria; <br>Glutamine, Glutamate, Aspartate and
Asparagine Biosynthesis fig|6666666.60966.peg.1862 CDS 1735929
1737425 3 + 1497 major facilitator -none- D23_1c1865 Neut_1736
superfamily MFS_1 fig|6666666.60966.peg.1863 CDS 1737575 1737841 2
+ 267 Mobile element protein -none- D23_1c1866 NA
fig|6666666.60966.peg.1864 CDS 1737835 1737975 1 + 141 Mobile
element protein -none- D23_1c1867 NA fig|6666666.60966.peg.1865 CDS
1738803 1738006 -3 - 798 Mobile element protein -none- D23_1c1868
Neut_1888 fig|6666666.60966.peg.1866 CDS 1739186 1738917 -2 - 270
Mobile element protein -none- D23_1c1869 Neut_2500
fig|6666666.60966.peg.1868 CDS 1740582 1739374 -3 - 1209
hypothetical protein -none- D23_1c1870 Neut_1740
fig|6666666.60966.peg.1869 CDS 1742717 1740588 -2 - 2130
Ferrichrome-iron -none- D23_1c1871 Neut_1741 receptor
fig|6666666.60966.peg.1870 CDS 1744008 1742806 -3 - 1203
Vibrioferrin -none- D23_1c1872 Neut_1742 decarboxylase protein PvsE
fig|6666666.60966.peg.1871 CDS 1745819 1744005 -2 - 1815
Vibrioferrin amide bond -none- D23_1c1873 Neut_1743 forming protein
PvsD @ Siderophore synthetase superfamily, group A
fig|6666666.60966.peg.1872 CDS 1747001 1745829 -2 - 1173
Vibrioferrin membrane- -none- D23_1c1874 Neut_1744 spanning
transport protein PvsC fig|6666666.60966.peg.1873 CDS 1748855
1747044 -2 - 1812 Anthrachelin -none- D23_1c1875 Neut_1745
biosynthesis protein AsbB @ Siderophore synthetase superfamily,
group C @ Siderophore synthetase component, ligase
fig|6666666.60966.peg.1874 CDS 1749327 1749151 -3 - 177 Mobile
element protein -none- D23_1c1876 Neut_1747
fig|6666666.60966.peg.1876 CDS 1750647 1749685 -3 - 963 Mobile
element protein -none- D23_1c1878 Neut_1278
fig|6666666.60966.peg.1877 CDS 1751012 1752274 2 + 1263
hypothetical protein -none- D23_1c1879 Neut_1749
fig|6666666.60966.peg.1878 CDS 1752303 1753133 3 + 831 Potassium
efflux system Potassium homeostasis D23_1c1880 NA KefA
protein/Small- conductance mechanosensitive channel
fig|6666666.60966.peg.1879 CDS 1753722 1753153 -3 - 570
hypothetical protein -none- D23_1c1881 NA
fig|6666666.60966.peg.1880 CDS 1753823 1754629 2 + 807 Glutamate
racemase Glutamine, Glutamate, D23_1c1882 Neut_1752 (EC 5.1.1.3)
Aspartate and Asparagine Biosynthesis; <br>Peptidoglycan
Biosynthesis fig|6666666.60966.peg.1881 CDS 1754733 1755689 3 + 957
Universal stress protein -none- D23_1c1883 Neut_1753
fig|6666666.60966.peg.1882 CDS 1756978 1755725 -1 - 1254 DNA repair
protein DNA repair, bacterial; D23_1c1884 Neut_1754 RadA
<br>Proteolysis in bacteria, ATP-dependent
fig|6666666.60966.peg.1883 CDS 1757073 1757201 3 + 129 hypothetical
protein -none- D23_1c1885 NA fig|6666666.60966.peg.1884 CDS 1758757
1757372 -1 - 1386 L-serine dehydratase Glycine and Serine
D23_1c1887 Neut_1760 (EC 4.3.1.17) Utilization; <br>Pyruvate
Alanine Serine Interconversions fig|6666666.60966.peg.1886 CDS
1759312 1760013 1 + 702 Serine protease Transcription initiation,
D23_1c1890 Neut_1761 precursor MucD/AlgY bacterial sigma factors
associated with sigma factor RpoE
fig|6666666.60966.peg.1887 CDS 1760622 1761584 3 + 963 Mobile
element protein -none- D23_1c1892 Neut_1278
fig|6666666.60966.peg.1888 CDS 1761643 1762524 1 + 882 FIG071646:
Sugar Cell wall related cluster D23_1c1893 Neut_1762 transferase
fig|6666666.60966.peg.1889 CDS 1762574 1764655 2 + 2082 Sensory
transduction -none- D23_1c1894 Neut_1763 histidine kinases
fig|6666666.60966.peg.1890 CDS 1764739 1766601 1 + 1863 Lipid A
export ATP- -none- D23_1c1895 Neut_1764 binding/permease protein
MsbA fig|6666666.60966.peg.1891 CDS 1769731 1766636 -1 - 3096
Cobalt-zinc-cadmium Cobalt-zinc-cadmium D23_1c1896 Neut_1765
resistance protein CzcA; resistance; <br>Cobalt- Cation
efflux system zinc-cadmium resistance protein CusA
fig|6666666.60966.peg.1892 CDS 1770897 1769734 -3 - 1164
Cobalt/zinc/cadmium Cobalt-zinc-cadmium D23_1c1897 Neut_1766 efflux
RND transporter, resistance membrane fusion protein, CzcB family
fig|6666666.60966.peg.1893 CDS 1772112 1770907 -3 - 1206 Heavy
metal RND efflux Cobalt-zinc-cadmium D23_1c1898 Neut_1767 outer
membrane resistance protein, CzcC family fig|6666666.60966.peg.1894
CDS 1773163 1772504 -1 - 660 FIG00859115: -none- D23_1c1899
Neut_1768 hypothetical protein fig|6666666.60966.peg.1895 CDS
1773250 1773996 1 + 747 Glycerophosphoryl CBSS- D23_1c1900
Neut_1769 diester 176299.4.peg.1996A; phosphodiesterase (EC
<br>Glycerol and 3.1.4.46) Glycerol-3-phosphate Uptake and
Utilization fig|6666666.60966.peg.1896 CDS 1774006 1775181 1 + 1176
Aerobic glycerol-3- Glycerol and Glycerol-3- D23_1c1901 Neut_1770
phosphate phosphate Uptake and dehydrogenase (EC Utilization;
1.1.5.3) <br>Glycerolipid and Glycerophospholipid Metabolism
in Bacteria; <br>Respiratory dehydrogenases 1
fig|6666666.60966.peg.1897 CDS 1775543 1775211 -2 - 333
FIG00859262: -none- D23_1c1902 Neut_1771 hypothetical protein
fig|6666666.60966.peg.1898 CDS 1776076 1775636 -1 - 441
FIG00859309: -none- D23_1c1903 Neut_1772 hypothetical protein
fig|6666666.60966.peg.1899 CDS 1777538 1776078 -2 - 1461
Dihydrolipoamide Dehydrogenase D23_1c1904 Neut_1773 dehydrogenase
of 2- complexes; <br>TCA oxoglutarate Cycle dehydrogenase (EC
1.8.1.4) fig|6666666.60966.peg.1900 CDS 1778658 1777612 -3 - 1047
Beta N-acetyl- Murein Hydrolases; D23_1c1905 Neut_1774
glucosaminidase (EC <br>Recycling of 3.2.1.52) Peptidoglycan
Amino Sugars fig|6666666.60966.peg.1901 CDS 1779038 1778661 -2 -
378 Holo-[acyl-carrier Fatty Acid Biosynthesis D23_1c1906 Neut_1775
protein] synthase (EC FASII 2.7.8.7) fig|6666666.60966.peg.1902 CDS
1779760 1779035 -1 - 726 Pyridoxine 5'- Pyridoxin (Vitamin B6)
D23_1c1907 Neut_1776 phosphate synthase (EC Biosynthesis 2.6.99.2)
fig|6666666.60966.peg.1903 CDS 1780768 1779878 -1 - 891 GTP-binding
protein Era Bacterial Cell Division; D23_1c1908 Neut_1777
<br>Glycyl-tRNA synthetase containing cluster;
<br>Universal GTPases fig|6666666.60966.peg.1904 CDS 1781583
1780846 -3 - 738 Ribonuclease III (EC RNA processing and D23_1c1909
Neut_1778 3.1.26.3) degradation, bacterial
fig|6666666.60966.peg.1905 CDS 1781963 1781580 -2 - 384 possible
-none- D23_1c1910 Neut_1779 transmembrane protein
fig|6666666.60966.peg.1906 CDS 1782802 1781999 -1 - 804 Signal
peptidase I (EC Signal peptidase D23_1c1911 Neut_1780 3.4.21.89)
fig|6666666.60966.peg.1907 CDS 1784670 1782874 -3 - 1797
Translation elongation Heat shock dnaK gene D23_1c1912 Neut_1781
factor LepA cluster extended; <br>Translation elongation
factors bacterial; <br>Universal GTPases
fig|6666666.60966.peg.1908 CDS 1784806 1784651 -1 - 156
hypothetical protein -none- D23_1c1913 NA
fig|6666666.60966.peg.1909 CDS 1785160 1784972 -1 - 189 COGs
COG0526 -none- D23_1c1914 Neut_1782 fig|6666666.60966.peg.1910 CDS
1786580 1785222 -2 - 1359 Serine protease Transcription initiation,
D23_1c1915 Neut_1783 precursor MucD/AlgY bacterial sigma factors
associated with sigma factor RpoE fig|6666666.60966.peg.1911 CDS
1787446 1786871 -1 - 576 InterPro IPR001687 -none- D23_1c1916
Neut_1784 COGs COG3073 fig|6666666.60966.peg.1912 CDS 1788062
1787460 -2 - 603 RNA polymerase sigma Transcription initiation,
D23_1c1917 Neut_1785 factor RpoE bacterial sigma factors
fig|6666666.60966.peg.1913 CDS 1789111 1788260 -1 - 852 Magnesium
and cobalt CBSS- D23_1c1919 Neut_1786 efflux protein CorC
56780.10.peg.1536; <br>Copper homeostasis: copper tolerance;
<br>Glycyl- tRNA synthetase containing cluster;
<br>Magnesium transport; <br>tRNA-
methylthiotransferase containing cluster fig|6666666.60966.peg.1914
CDS 1789590 1789165 -3 - 426 Metal-dependent CBSS- D23_1c1920
Neut_1787 hydrolase YbeY, 56780.10.peg.1536; involved in rRNA
and/or <br>Glycyl-tRNA ribosome maturation synthetase
containing and assembly cluster; <br>tRNA-
methylthiotransferase containing cluster fig|6666666.60966.peg.1915
CDS 1790629 1789619 -1 - 1011 Phosphate starvation- -none-
D23_1c1921 Neut_1788 inducible ATPase PhoH with RNA binding motif
fig|6666666.60966.peg.1916 CDS 1792022 1790691 -2 - 1332
tRNA-i(6)A37 Methylthiotransferases; D23_1c1922 Neut_1789
methylthiotransferase <br>tRNA- methylthiotransferase
containing cluster; <br>tRNA modification Bacteria;
<br>tRNA processing fig|6666666.60966.peg.1917 CDS 1793040
1792321 -3 - 720 Cytochrome c-type -none- D23_1c1923 Neut_1790
protein TorY fig|6666666.60966.peg.1918 CDS 1793750 1793043 -2 -
708 Cytochrome c family -none- D23_1c1924 Neut_2333 protein
fig|6666666.60966.peg.1919 CDS 1794933 1793812 -3 - 1122
FIG00859557: -none- D23_1c1925 Neut_1792 hypothetical protein
fig|6666666.60966.peg.1920 CDS 1796642 1794930 -2 - 1713
Hydroxylamine -none- D23_1c1926 Neut_2335 oxidoreductase precursor
(EC 1.7.3.4) fig|6666666.60966.peg.1921 CDS 1801076 1796862 -2 -
4215 DNA-directed RNA Mycobacterium D23_1c1927 Neut_1794 polymerase
beta' virulence operon subunit (EC 2.7.7.6) involved in DNA
transcription; <br>RNA polymerase bacterial
fig|6666666.60966.peg.1922 CDS 1805314 1801235 -1 - 4080
DNA-directed RNA Mycobacterium D23_1c1928 Neut_1795 polymerase beta
virulence operon subunit (EC 2.7.7.6) involved in DNA
transcription; <br>RNA polymerase bacterial
fig|6666666.60966.peg.1923 CDS 1806051 1805680 -3 - 372 LSU
ribosomal protein LSU ribosomal proteins D23_1c1929 Neut_1796
L7/L12 (P1/P2) cluster fig|6666666.60966.peg.1924 CDS 1806648
1806133 -3 - 516 LSU ribosomal protein LSU ribosomal proteins
D23_1c1930 Neut_1797 L10p (P0) cluster fig|6666666.60966.peg.1925
CDS 1807793 1807098 -2 - 696 LSU ribosomal protein LSU ribosomal
proteins D23_1c1931 Neut_1798 Lip (L10Ae) cluster
fig|6666666.60966.peg.1926 CDS 1808121 1807795 -3 - 327 LSU
ribosomal protein LSU ribosomal proteins D23_1c1932 Neut_1799 L11p
(L12e) cluster fig|6666666.60966.peg.1927 CDS 1808877 1808344 -3 -
534 Transcription LSU ribosomal proteins D23_1c1934 Neut_1800
antitermination protein cluster; NusG <br>Transcription
factors bacterial fig|6666666.60966.peg.1928 CDS 1809240 1808896 -3
- 345 Preprotein translocase LSU ribosomal proteins D23_1c1935
Neut_1801 subunit SecE (TC cluster 3.A.5.1.1)
fig|6666666.60966.peg.1929 CDS 1810674 1809484 -3 - 1191
Translation elongation Mycobacterium D23_1c1937 Neut_1802 factor Tu
virulence operon involved in protein synthesis (SSU ribosomal
proteins); <br>Translation elongation factors bacterial;
<br>Universal GTPases fig|6666666.60966.peg.1930 CDS 1813382
1811220 -2 - 2163 Type IV pilus biogenesis -none- D23_1c1941
Neut_1803 fig|6666666.60966.peg.1931 CDS 1813906 1813379 -1 - 528
Type IV pilus biogenesis -none- D23_1c1942 Neut_1804 protein PilP
fig|6666666.60966.peg.1932 CDS 1814553 1813903 -3 - 651 Type IV
pilus biogenesis -none- D23_1c1943 Neut_1805 protein PilO
fig|6666666.60966.peg.1933 CDS 1815161 1814550 -2 - 612 Type IV
pilus biogenesis -none- D23_1c1944 Neut_1806 protein PilN
fig|6666666.60966.peg.1934 CDS 1816207 1815158 -1 - 1050 Type IV
pilus biogenesis -none- D23_1c1945 Neut_1807 protein PilM
fig|6666666.60966.peg.1936 CDS 1816441 1818753 1 + 2313
Multimodular Peptidoglycan D23_1c1947 Neut_1808 transpeptidase-
Biosynthesis transglycosylase (EC 2.4.1.129) (EC 3.4.--.--)
fig|6666666.60966.peg.1937 CDS 1819961 1819041 -2 - 921
Deacetylases, including -none- D23_1c1948 Neut_1809 yeast histone
deacetylase and acetoin utilization protein
fig|6666666.60966.peg.1939 CDS 1820319 1820170 -3 - 150
hypothetical protein -none- D23_1c1949 Neut_1810
fig|6666666.60966.peg.1941 CDS 1820799 1820638 -3 - 162 Addiction
module -none- D23_1c1950 Neut_1811 antidote protein
fig|6666666.60966.peg.1942 CDS 1821096 1820914 -3 - 183
hypothetical protein -none- D23_1c1951 Neut_1812
fig|6666666.60966.peg.1943 CDS 1821848 1821985 2 + 138 Prevent host
death Phd-Doc, YdcE-YdcD D23_1c1953 NA protein, Phd antitoxin
toxin-antitoxin (programmed cell death) systems
fig|6666666.60966.peg.1944 CDS 1821982 1822278 1 + 297 Death on
curing Phd-Doc, YdcE-YdcD D23_1c1954 NA protein, Doc toxin
toxin-antitoxin (programmed cell death) systems
fig|6666666.60966.peg.1945 CDS 1822608 1822423 -3 - 186
hypothetical protein -none- D23_1c1955 Neut_1816
fig|6666666.60966.peg.1946 CDS 1822933 1822688 -1 - 246
hypothetical protein -none- D23_1c1956 Neut_1817
fig|6666666.60966.peg.1947 CDS 1823491 1823150 -1 - 342 Predicted
-none- D23_1c1957 NA transcriptional regulator
fig|6666666.60966.peg.1948 CDS 1823708 1823484 -2 - 225
Phage-related protein -none- D23_1c1958 NA
fig|6666666.60966.peg.1952 CDS 1824892 1824704 -1 - 189
hypothetical protein -none- D23_1c1959 NA
fig|6666666.60966.peg.1953 CDS 1825371 1825036 -3 - 336 Mobile
element protein -none- D23_1c1960 Neut_1624
fig|6666666.60966.peg.1954 CDS 1825828 1825352 -1 - 477 Mobile
element protein -none- D23_1c1961 Neut_1888
fig|6666666.60966.peg.1955 CDS 1826127 1825942 -3 - 186 Mobile
element protein -none- D23_1c1962 Neut_2500
fig|6666666.60966.peg.1956 CDS 1826660 1826472 -2 - 189 Mobile
element protein -none- D23_1c1963 Neut_1821
fig|6666666.60966.peg.1958 CDS 1827279 1826920 -3 - 360 Flagellin
protein FlaG Flagellum D23_1c1964 Neut_1822
fig|6666666.60966.peg.1959 CDS 1827931 1827644 -1 - 288
Excinuclease ABC, C -none- D23_1c1965 Neut_1823 subunit-like
fig|6666666.60966.peg.1960 CDS 1829557 1828115 -1 - 1443 Flagellin
protein FlaB Flagellum; <br>Flagellum D23_1c1967 Neut_1824 in
Campylobacter fig|6666666.60966.peg.1961 CDS 1830108 1830230 3 +
123 hypothetical protein -none- D23_1c1968 NA
fig|6666666.60966.peg.1962 CDS 1831067 1830276 -2 - 792 Mobile
element protein -none- D23_1c1969 Neut_1888
fig|6666666.60966.peg.1963 CDS 1831366 1831181 -1 - 186 Mobile
element protein -none- D23_1c1970 Neut_2500
fig|6666666.60966.peg.1964 CDS 1831759 1831616 -1 - 144
hypothetical protein -none- D23_1c1971 NA
fig|6666666.60966.peg.1965 CDS 1832465 1831749 -2 - 717
hypothetical protein -none- D23_1c1972 Neut_1827
fig|6666666.60966.peg.1967 CDS 1835117 1833291 -2 - 1827 DNA
mismatch repair DNA repair, bacterial D23_1c1973 Neut_1828 protein
MutL MutL-MutS system fig|6666666.60966.peg.1968 CDS 1835287
1835946 1 + 660 Ribose 5-phosphate Calvin-Benson cycle; D23_1c1974
Neut_1829 isomerase A (EC 5.3.1.6) <br>D-ribose utilization;
<br>Pentose phosphate pathway fig|6666666.60966.peg.1969 CDS
1836022 1836150 1 + 129 hypothetical protein -none- D23_1c1975 NA
fig|6666666.60966.peg.1970 CDS 1836140 1836859 2 + 720 Phosphate
transport High affinity phosphate D23_1c1976 Neut_1830 system
regulatory transporter and control protein PhoU of PHO regulon;
<br>Phosphate metabolism fig|6666666.60966.peg.1971 CDS
1836819 1838420 3 + 1602 Exopolyphosphatase Phosphate metabolism;
D23_1c1977 Neut_1831 (EC 3.6.1.11) <br>Polyphosphate
fig|6666666.60966.peg.1972 CDS 1838878 1838429 -1 - 450 Type IV
pilus biogenesis -none- D23_1c1978 Neut_1832 protein PilE
fig|6666666.60966.peg.1973 CDS 1842290 1838922 -2 - 3369 Type IV
fimbrial -none- D23_1c1979 Neut_1833 biogenesis protein PilY1
fig|6666666.60966.peg.1974 CDS 1843213 1842362 -1 - 852 Type IV
fimbrial -none- D23_1c1980 Neut_1834 biogenesis protein PilX
fig|6666666.60966.peg.1975 CDS 1844303 1843239 -2 - 1065 Type IV
fimbrial -none- D23_1c1981 Neut_1835 biogenesis protein PilW
fig|6666666.60966.peg.1976 CDS 1844806 1844321 -1 - 486 Type IV
fimbrial -none- D23_1c1982 Neut_1836 biogenesis protein PilV
fig|6666666.60966.peg.1977 CDS 1845339 1844830 -3 - 510 Type IV
fimbrial -none- D23_1c1983 Neut_1837 biogenesis protein FimT
fig|6666666.60966.peg.1978 CDS 1845616 1845783 1 + 168 hypothetical
protein -none- D23_1c1984 NA fig|6666666.60966.peg.1979 CDS 1846400
1845768 -2 - 633 DNA-binding response -none- D23_1c1985 Neut_1839
regulator, LuxR family fig|6666666.60966.peg.1980 CDS 1847948
1846452 -2 - 1497 Sensory box histidine -none- D23_1c1986 Neut_1840
kinase/response regulator fig|6666666.60966.peg.1981 CDS 1848084
1848206 3 + 123 hypothetical protein -none- D23_1c1987 NA
fig|6666666.60966.peg.1982 CDS 1850161 1848614 -1 - 1548 pilin
glycosylation -none- D23_1c1988 Neut_1841 enzyme, putative
fig|6666666.60966.peg.1985 CDS 1852587 1850815 -3 - 1773 Gamma-
Glutathione: D23_1c1989 Neut_1843 glutamyltranspeptidase
Biosynthesis and (EC 2.3.2.2) gamma-glutamyl cycle
fig|6666666.60966.peg.1986 CDS 1853865 1852903 -3 - 963 Mobile
element protein -none- D23_1c1990 Neut_1746
fig|6666666.60966.peg.1987 CDS 1854432 1853923 -3 - 510 putative
-none- D23_1c1991 Neut_1845 transmembrane protein
fig|6666666.60966.peg.1988 CDS 1855175 1854606 -2 - 570
hypothetical protein -none- D23_1c1992 Neut_1849
fig|6666666.60966.peg.1989 CDS 1855822 1855421 -1 - 402 Glyoxalase
family protein -none- D23_1c1993 Neut_1850
fig|6666666.60966.peg.1990 CDS 1855948 1855835 -1 - 114
hypothetical protein -none- D23_1c1994 NA
fig|6666666.60966.peg.1991 CDS 1856595 1856026 -3 - 570
hypothetical protein -none- D23_1c1995 Neut_1851
fig|6666666.60966.peg.1992 CDS 1856572 1856703 1 + 132 hypothetical
protein -none- D23_1c1996 NA fig|6666666.60966.peg.1993 CDS 1858627
1856756 -1 - 1872 hypothetical protein -none- D23_1c1997 Neut_1853
fig|6666666.60966.peg.1994 CDS 1860549 1858642 -3 - 1908
hypothetical protein -none- D23_1c1998 Neut_1854
fig|6666666.60966.peg.1995 CDS 1860536 1860667 2 + 132 hypothetical
protein -none- D23_1c1999 NA fig|6666666.60966.peg.1996 CDS 1861687
1860761 -1 - 927 Expressed protein -none- D23_1c2000 Neut_1857
precursor fig|6666666.60966.peg.1997 CDS 1862145 1861684 -3 - 462
hypothetical protein -none- D23_1c2001 Neut_1858
fig|6666666.60966.peg.1998 CDS 1865471 1862334 -2 - 3138 Proline
dehydrogenase Proline, 4- D23_1c2002 Neut_1859 (EC 1.5.99.8)
(Proline hydroxyproline uptake oxidase)/Delta-1- and utilization;
pyrroline-5-carboxylate <br>Respiratory dehydrogenase (EC
dehydrogenases 1 1.5.1.12) fig|6666666.60966.peg.2000 CDS 1865859
1865701 -3 - 159 hypothetical protein -none- D23_1c2003 Neut_1860
fig|6666666.60966.peg.2001 CDS 1866618 1866328 -3 - 291
hypothetical protein -none- D23_1c2004 NA
fig|6666666.60966.peg.2002 CDS 1866574 1866861 1 + 288 Probable
-none- D23_1c2005 Neut_1861 transmembrane protein
fig|6666666.60966.peg.2004 CDS 1867176 1867955 3 + 780 hypothetical
protein -none- D23_1c2006 Neut_1863 fig|6666666.60966.peg.2005 CDS
1870128 1868077 -3 - 2052 Serine peptidase -none- D23_1c2007
Neut_1864 fig|6666666.60966.peg.2006 CDS 1870373 1870546 2 + 174
hypothetical protein -none- D23_1c2008 NA
fig|6666666.60966.peg.2007 CDS 1871555 1870827 -2 - 729
1-acyl-sn-glycerol-3- Glycerolipid and D23_1c2009 Neut_1866
phosphate Glycerophospholipid acyltransferase (EC Metabolism in
Bacteria 2.3.1.51) fig|6666666.60966.peg.2008 CDS 1872097 1871555
-1 - 543 Histidinol-phosphatase Histidine Biosynthesis D23_1c2010
Neut_1867 (EC 3.1.3.15) fig|6666666.60966.peg.2009 CDS 1874271
1872124 -3 - 2148 Glycyl-tRNA synthetase Glycyl-tRNA synthetase;
D23_1c2011 Neut_1868 beta chain (EC 6.1.1.14) <br>Glycyl-tRNA
synthetase containing cluster; <br>tRNA aminoacylation, Gly
fig|6666666.60966.peg.2010 CDS 1875191 1874268 -2 - 924 Glycyl-tRNA
synthetase Glycyl-tRNA synthetase; D23_1c2012 Neut_1869 alpha chain
(EC <br>Glycyl-tRNA 6.1.1.14) synthetase containing cluster;
<br>tRNA aminoacylation, Gly fig|6666666.60966.peg.2011 CDS
1876717 1875224 -1 - 1494 Apolipoprotein N- Copper homeostasis:
D23_1c2013 Neut_1870 acyltransferase (EC copper tolerance;
2.3.1.--)/Copper <br>Lipoprotein homeostasis protein
Biosynthesis; <br>tRNA- CutE methylthiotransferase containing
cluster; <br>tRNA- methylthiotransferase containing cluster
fig|6666666.60966.peg.2012 CDS 1877111 1876773 -2 - 339
FIG00859587: -none- D23_1c2014 Neut_1871 hypothetical protein
fig|6666666.60966.peg.2013 CDS 1877265 1877122 -3 - 144
hypothetical protein -none- D23_1c2015 NA
fig|6666666.60966.peg.2014 CDS 1877596 1879305 1 + 1710 Multicopper
oxidase Copper homeostasis D23_1c2016 Neut_1872
fig|6666666.60966.peg.2015 CDS 1879305 1880399 3 + 1095 Zinc ABC
transporter, -none- D23_1c2017 Neut_1873 periplasmic-binding
protein ZnuA fig|6666666.60966.peg.2016 CDS 1881044 1880847 -2 -
198 hypothetical protein -none- D23_1c2018 NA
fig|6666666.60966.peg.2017 CDS 1881486 1881962 3 + 477 Cytochrome c
oxidase Terminal cytochrome C D23_1c2020 Neut_1874 (B(O/a)3-type)
chain II oxidases (EC 1.9.3.1) fig|6666666.60966.peg.2018 CDS
1882000 1883478 1 + 1479 Cytochrome c oxidase Terminal cytochrome C
D23_1c2021 Neut_1875 (B(O/a)3-type) chain I oxidases (EC 1.9.3.1)
fig|6666666.60966.peg.2019 CDS 1883574 1884203 3 + 630 Cytochrome
oxidase Biogenesis of D23_1c2022 Neut_1876 biogenesis protein
cytochrome c oxidases Sco1/SenC/PrrC, putative copper
metallochaperone fig|6666666.60966.peg.2020 CDS 1884187 1884756 1 +
570 hypothetical -none- D23_1c2023 Neut_1877 cytochrome oxidase
associated membrane protein fig|6666666.60966.peg.2021 CDS 1885726
1884809 -1 - 918 Nitrite transporter from -none- D23_1c2024
Neut_1878 formate/nitrite family fig|6666666.60966.peg.2022 CDS
1887084 1886077 -3 - 1008 UDP-glucose 4- CBSS- D23_1c2026 Neut_1879
epimerase (EC 5.1.3.2) 296591.1.peg.2330; <br>N-linked
Glycosylation in Bacteria; <br>Rhamnose containing glycans
fig|6666666.60966.peg.2023 CDS 1888047 1887160 -3 - 888
Glucose-1-phosphate Rhamnose containing D23_1c2027 Neut_1880
thymidylyltransferase glycans; <br>dTDP- (EC 2.7.7.24)
rhamnose synthesis fig|6666666.60966.peg.2024 CDS 1888279 1888148
-1 - 132 hypothetical protein -none- D23_1c2028 NA
fig|6666666.60966.peg.2025 CDS 1888278 1889198 3 + 921 2-hydroxy-3-
Glycerate metabolism; D23_1c2029 Neut_1881 oxopropionate
<br>Photorespiration reductase (EC 1.1.1.60) (oxidative C2
cycle) fig|6666666.60966.peg.2026 CDS 1889188 1890642 1 + 1455
Glycolate Glycolate, glyoxylate D23_1c2030 Neut_1882 dehydrogenase
(EC interconversions; 1.1.99.14), subunit GlcD
<br>Photorespiration (oxidative C2 cycle)
fig|6666666.60966.peg.2027 CDS 1890667 1891767 1 + 1101 Glycolate
Glycolate, glyoxylate D23_1c2031 Neut_1883 dehydrogenase (EC
interconversions; 1.1.99.14), FAD-binding
<br>Photorespiration subunit GlcE (oxidative C2 cycle)
fig|6666666.60966.peg.2028 CDS 1891771 1893039 1 + 1269 Glycolate
Glycolate, glyoxylate D23_1c2032 Neut_1884 dehydrogenase (EC
interconversions; 1.1.99.14), iron-sulfur
<br>Photorespiration subunit GlcF (oxidative C2 cycle)
fig|6666666.60966.peg.2029 CDS 1893781 1893065 -1 - 717 Putative
predicted Restriction-Modification D23_1c2033 Neut_1885
metal-dependent System hydrolase fig|6666666.60966.peg.2030 CDS
1894582 1893806 -1 - 777 5'- Adenosyl nucleosidases; D23_1c2034
Neut_1886 methylthioadenosine <br>Adenosyl nucleosidase (EC
nucleosidases; 3.2.2.16)/S- <br>CBSS- adenosylhomocysteine
320388.3.peg.3759; nucleosidase (EC <br>CBSS- 3.2.2.9)
320388.3.peg.3759; <br>Methionine Biosynthesis;
<br>Methionine Degradation; <br>Polyamine Metabolism
fig|6666666.60966.peg.2031 CDS 1896116 1894656 -2 - 1461
Exodeoxyribonuclease I DNA Repair Base D23_1c2035 Neut_1887 (EC
3.1.11.1) Excision fig|6666666.60966.peg.2032 CDS 1896438 1897133 3
+ 696 FIG00657740: -none- D23_1c2036 Neut_1890 hypothetical protein
fig|6666666.60966.peg.2033 CDS 1898282 1897428 -2 - 855 5,10-
5-FCL-like protein; D23_1c2038 Neut_1891 methylenetetrahydrofolate
<br>Methionine reductase (EC Biosynthesis; <br>One-
1.5.1.20) carbon metabolism by tetrahydropterines
fig|6666666.60966.peg.2034 CDS 1898327 1898494 2 + 168
hypothetical
protein -none- D23_1c2039 NA fig|6666666.60966.peg.2035 CDS 1899999
1898563 -3 - 1437 Adenosylhomocysteinase Methionine D23_1c2041
Neut_1892 (EC 3.3.1.1) Biosynthesis; <br>Methionine
Degradation fig|6666666.60966.peg.2036 CDS 1901244 1900135 -3 -
1110 S-adenosylmethionine Methionine D23_1c2042 Neut_1893
synthetase (EC 2.5.1.6) Biosynthesis; <br>Methionine
Degradation fig|6666666.60966.peg.2037 CDS 1901543 1902289 2 + 747
Short chain -none- D23_1c2043 Neut_1894 dehydrogenase
fig|6666666.60966.peg.2038 CDS 1902336 1902812 3 + 477 ATPase YjeE,
predicted -none- D23_1c2044 Neut_1895 to have essential role in
cell wall biosynthesis fig|6666666.60966.peg.2039 CDS 1903046
1904116 2 + 1071 N-acetylmuramoyl-L- Murein Hydrolases; D23_1c2045
Neut_1896 alanine amidase (EC <br>Recycling of 3.5.1.28)
Peptidoglycan Amino Acids; <br>Zinc regulated enzymes
fig|6666666.60966.peg.2040 CDS 1904922 1904170 -3 - 753
FIG00859340: -none- D23_1c2046 Neut_1897 hypothetical protein
fig|6666666.60966.peg.2041 CDS 1905860 1904919 -2 - 942 Ribosomal
protein L11 Heat shock dnaK gene D23_1c2047 Neut_1898
methyltransferase (EC cluster extended; 2.1.1.--)
<br>Ribosome biogenesis bacterial fig|6666666.60966.peg.2042
CDS 1907254 1905896 -1 - 1359 Biotin carboxylase of Fatty Acid
Biosynthesis D23_1c2048 Neut_1899 acetyl-CoA carboxylase FASII (EC
6.3.4.14) fig|6666666.60966.peg.2043 CDS 1907784 1907326 -3 - 459
Biotin carboxyl carrier Fatty Acid Biosynthesis D23_1c2049
Neut_1900 protein of acetyl-CoA FASII carboxylase
fig|6666666.60966.peg.2045 CDS 1908294 1907989 -3 - 306
3-dehydroquinate Chorismate Synthesis; D23_1c2050 Neut_1901
dehydratase II (EC <br>Common Pathway 4.2.1.10) For Synthesis
of Aromatic Compounds (DAHP synthase to chorismate);
<br>Quinate degradation fig|6666666.60966.peg.2047 CDS
1908606 1909715 3 + 1110 Glycine oxidase ThiO Thiamin biosynthesis
D23_1c2051 Neut_1902 (EC 1.4.3.19) fig|6666666.60966.peg.2048 CDS
1910693 1909722 -2 - 972 4-hydroxy-3-methylbut- Isoprenoid
Biosynthesis; D23_1c2052 Neut_1903 2-enyl diphosphate
<br>Nonmevalonate reductase (EC 1.17.1.2) Branch of
Isoprenoid Biosynthesis fig|6666666.60966.peg.2049 CDS 1910983
1911267 1 + 285 FIG00858797: -none- D23_1c2053 Neut_1904
hypothetical protein fig|6666666.60966.peg.2050 CDS 1911307 1912386
1 + 1080 Histidinol-phosphate Histidine Biosynthesis D23_1c2054
Neut_1905 aminotransferase (EC 2.6.1.9) fig|6666666.60966.peg.2051
CDS 1912429 1913016 1 + 588 Imidazoleglycerol- Histidine
Biosynthesis D23_1c2055 Neut_1906 phosphate dehydratase (EC
4.2.1.19) fig|6666666.60966.peg.2052 CDS 1913079 1913687 3 + 609
Imidazole glycerol Histidine Biosynthesis D23_1c2056 Neut_1907
phosphate synthase amidotransferase subunit (EC 2.4.2.--)
fig|6666666.60966.peg.2053 CDS 1913772 1914518 3 + 747
Phosphoribosylformimino- Chorismate: D23_1c2057 Neut_1908
5-aminoimidazole Intermediate for carboxamide ribotide synthesis of
Tryptophan, isomerase (EC 5.3.1.16) PAPA antibiotics, PABA,
3-hydroxyanthranilate and more.; <br>Histidine Biosynthesis
fig|6666666.60966.peg.2054 CDS 1914604 1915380 1 + 777 Imidazole
glycerol Histidine Biosynthesis D23_1c2058 Neut_1909 phosphate
synthase cyclase subunit (EC 4.1.3.--) fig|6666666.60966.peg.2055
CDS 1915424 1915909 2 + 486 Phosphoribosyl-AMP Histidine
Biosynthesis; D23_1c2059 Neut_1910 cyclohydrolase (EC
<br>Zinc regulated 3.5.4.19) enzymes
fig|6666666.60966.peg.2056 CDS 1915906 1916259 1 + 354
Phosphoribosyl-ATP Histidine Biosynthesis; D23_1c2060 Neut_1911
pyrophosphatase (EC <br>Riboflavin synthesis 3.6.1.31)
cluster fig|6666666.60966.peg.2057 CDS 1916261 1916611 2 + 351
FIG146285: -none- D23_1c2061 Neut_1912 Diadenosine tetraphosphate
(Ap4A) hydrolase and other HIT family hydrolases
fig|6666666.60966.peg.2058 CDS 1916631 1916864 3 + 234
Twin-arginine Cluster-based Subsystem D23_1c2062 Neut_1913
translocation protein Grouping Hypotheticals- TatA perhaps
Proteosome Related; <br>Twin- arginine translocation system
fig|6666666.60966.peg.2060 CDS 1916950 1917342 1 + 393
Twin-arginine Twin-arginine D23_1c2063 Neut_1914 translocation
protein translocation system TatB fig|6666666.60966.peg.2061 CDS
1917433 1918209 1 + 777 Twin-arginine Cluster-based Subsystem
D23_1c2064 Neut_1915 translocation protein Grouping Hypotheticals-
TatC perhaps Proteosome Related; <br>Twin- arginine
translocation system fig|6666666.60966.peg.2062 CDS 1918395 1920518
3 + 2124 Outer membrane -none- D23_1c2065 Neut_1916 vitamin B12
receptor BtuB fig|6666666.60966.peg.2063 CDS 1920528 1921118 3 +
591 Optional hypothetical -none- D23_1c2066 Neut_1917 component of
the B12 transporter BtuM fig|6666666.60966.peg.2064 CDS 1921118
1921726 2 + 609 Cob(I)alamin -none- D23_1c2067 Neut_1918
adenosyltransferase (EC 2.5.1.17) fig|6666666.60966.peg.2065 CDS
1922713 1922826 1 + 114 hypothetical protein -none- D23_1c2069 NA
fig|6666666.60966.peg.2067 CDS 1923447 1924253 3 + 807 Cytochrome
bd-type -none- D23_1c2070 Neut_1920 quinol oxidase, subunit 1
fig|6666666.60966.peg.2068 CDS 1926393 1924288 -3 - 2106
Methionyl-tRNA Scaffold proteins for D23_1c2071 Neut_1921
synthetase (EC 6.1.1.10) [4Fe--4S] cluster assembly (MRP family);
<br>tRNA aminoacylation, Met fig|6666666.60966.peg.2069 CDS
1926506 1926390 -2 - 117 hypothetical protein -none- D23_1c2072 NA
fig|6666666.60966.peg.2070 CDS 1926499 1927584 1 + 1086 Scaffold
protein for Scaffold proteins for D23_1c2073 Neut_1922 [4Fe--4S]
cluster [4Fe--4S] cluster assembly ApbC, MRP- assembly (MRP family)
like fig|6666666.60966.peg.2071 CDS 1927630 1928163 1 + 534
Deoxycytidine pyrimidine conversions D23_1c2074 Neut_1923
triphosphate deaminase (EC 3.5.4.13) fig|6666666.60966.peg.2072 CDS
1928619 1928251 -3 - 369 COGs COG1917 -none- D23_1c2075 Neut_1924
fig|6666666.60966.peg.2073 CDS 1929401 1928631 -2 - 771 Inner
membrane -none- D23_1c2076 Neut_1925 protein
fig|6666666.60966.peg.2074 CDS 1929596 1929889 2 + 294 Mobile
element protein -none- D23_1c2077 Neut_1719
fig|6666666.60966.peg.2075 CDS 1929988 1930866 1 + 879 Mobile
element protein -none- D23_1c2078 Neut_1720
fig|6666666.60966.peg.2076 CDS 1930961 1933699 2 + 2739 Ca ion
P-type ATPase -none- D23_1c2079 Neut_1926
fig|6666666.60966.peg.2078 CDS 1934003 1934323 2 + 321 hypothetical
protein -none- D23_1c2080 Neut_1927 fig|6666666.60966.peg.2079 CDS
1935608 1934517 -2 - 1092 Prophage Lp2 protein 6 -none- D23_1c2081
Neut_1928 fig|6666666.60966.peg.2081 CDS 1935893 1936396 2 + 504
ABC transporter ATP- -none- D23_1c2083 Neut_1936 binding protein
YvcR fig|6666666.60966.peg.2083 CDS 1936587 1936880 3 + 294 Mobile
element protein -none- D23_1c2085 Neut_1719
fig|6666666.60966.peg.2084 CDS 1936979 1937857 2 + 879 Mobile
element protein -none- D23_1c2086 Neut_1720
fig|6666666.60966.peg.2085 CDS 1938082 1937936 -1 - 147
hypothetical protein -none- D23_1c2087 Neut_1937
fig|6666666.60966.peg.2086 CDS 1938637 1938188 -1 - 450 Ferric
uptake regulation Bacterial RNA- D23_1c2088 Neut_1938 protein FUR
metabolizing Zn- dependent hydrolases; <br>Oxidative stress
fig|6666666.60966.peg.2087 CDS 1938848 1939330 2 + 483 Outer
membrane Lipopolysaccharide D23_1c2089 Neut_1939 lipoprotein SmpA,
a assembly component of the essential YaeT outer- membrane protein
assembly complex fig|6666666.60966.peg.2088 CDS 1939327 1940133 1 +
807 Dihydrodipicolinate -none- D23_1c2090 Neut_1940 reductase (EC
1.3.1.26) fig|6666666.60966.peg.2089 CDS 1941855 1940347 -3 - 1509
ATPase -none- D23_1c2091 Neut_1941 fig|6666666.60966.peg.2090 CDS
1942209 1942087 -3 - 123 hypothetical protein -none- D23_1c2092 NA
fig|6666666.60966.peg.2091 CDS 1942220 1942459 2 + 240 Type I
restriction- Restriction-Modification D23_1c2093 Neut_1942
modification system, System; <br>Type I DNA-methyltransferase
Restriction-Modification subunit M (EC 2.1.1.72)
fig|6666666.60966.peg.2092 CDS 1942456 1942860 1 + 405 Cell
filamentation -none- D23_1c2094 Neut_1943 protein fic
fig|6666666.60966.peg.2093 CDS 1942823 1943278 2 + 456 Mobile
element protein -none- D23_1c2095 Neut_2502
fig|6666666.60966.peg.2094 CDS 1943305 1944786 1 + 1482 Outer
membrane -none- D23_1c2096 Neut_1945 component of tripartite
multidrug resistance system fig|6666666.60966.peg.2095 CDS 1944830
1946014 2 + 1185 Membrane fusion Multidrug Resistance D23_1c2097
Neut_1946 protein of RND family Efflux Pumps multidrug efflux pump
fig|6666666.60966.peg.2096 CDS 1946018 1949131 2 + 3114 RND efflux
system, Multidrug Resistance D23_1c2098 Neut_1947 inner membrane
Efflux Pumps transporter CmeB fig|6666666.60966.peg.2097 CDS
1949252 1949386 2 + 135 Type I restriction-
Restriction-Modification D23_1c2099 NA modification system, System;
<br>Type I restriction subunit R (EC Restriction-Modification
3.1.21.3) fig|6666666.60966.peg.2098 CDS 1949446 1950246 1 + 801
Bis(5'-nucleosyl)- EC49-61 D23_1c2100 Neut_1949 tetraphosphatase,
symmetrical (EC 3.6.1.41) fig|6666666.60966.peg.2099 CDS 1951009
1950200 -1 - 810 1-acyl-sn-glycerol-3- Glycerolipid and D23_1c2101
Neut_1950 phosphate Glycerophospholipid acyltransferase (EC
Metabolism in Bacteria 2.3.1.51) fig|6666666.60966.peg.2100 CDS
1952008 1951073 -1 - 936 InterPro IPR002173 -none- D23_1c2103
Neut_1951 COGs COG0524 fig|6666666.60966.peg.2101 CDS 1953491
1952040 -2 - 1452 Glycine dehydrogenase Glycine and Serine
D23_1c2104 Neut_1952 [decarboxylating] Utilization;
<br>Glycine (glycine cleavage cleavage system; system P2
protein) (EC <br>Photorespiration 1.4.4.2) (oxidative C2
cycle) fig|6666666.60966.peg.2102 CDS 1954921 1953566 -1 - 1356
Glycine dehydrogenase Glycine and Serine D23_1c2105 Neut_1953
[decarboxylating] Utilization; <br>Glycine (glycine cleavage
cleavage system; system P1 protein) (EC <br>Photorespiration
1.4.4.2) (oxidative C2 cycle) fig|6666666.60966.peg.2103 CDS
1955520 1955131 -3 - 390 Glycine cleavage system Glycine and Serine
D23_1c2106 Neut_1954 H protein Utilization; <br>Glycine
cleavage system; <br>Photorespiration (oxidative C2 cycle)
fig|6666666.60966.peg.2104 CDS 1956682 1955591 -1 - 1092
Aminomethyltransferase CBSS-87626.3.peg.3639; D23_1c2107 Neut_1955
(glycine cleavage <br>Glycine and Serine system T protein)
(EC Utilization; <br>Glycine 2.1.2.10) cleavage system;
<br>Photorespiration (oxidative C2 cycle)
fig|6666666.60966.peg.2106 CDS 1957270 1957133 -1 - 138
hypothetical protein -none- D23_1c2108 NA
fig|6666666.60966.peg.2107 CDS 1958337 1957420 -3 - 918
Coproporphyrinogen III Heme and Siroheme D23_1c2109 Neut_1956
oxidase, aerobic (EC Biosynthesis 1.3.3.3)
fig|6666666.60966.peg.2108 CDS 1958499 1959671 3 + 1173 Chorismate
synthase Chorismate Synthesis; D23_1c2110 Neut_1957 (EC 4.2.3.5)
<br>Common Pathway For Synthesis of Aromatic Compounds (DAHP
synthase to chorismate) fig|6666666.60966.peg.2110 CDS 1960360
1961133 1 + 774 IncF plasmid -none- D23_1c2111 Neut_1959
conjugative transfer surface exclusion protein TraT
fig|6666666.60966.peg.2111 CDS 1961191 1961517 1 + 327 hypothetical
protein -none- D23_1c2112 NA fig|6666666.60966.peg.2112 CDS 1961582
1962544 2 + 963 Mobile element protein -none- D23_1c2114 Neut_1862
fig|6666666.60966.peg.2113 CDS 1962848 1962729 -2 - 120
hypothetical protein -none- D23_1c2115 NA
fig|6666666.60966.peg.2115 CDS 1965546 1963441 -3 - 2106
Ferrichrome-iron -none- D23_1c2116 Neut_1962 receptor
fig|6666666.60966.peg.2118 CDS 1967221 1966565 -1 - 657 Protein of
unknown -none- D23_1c2119 Neut_1964 function DUF208
fig|6666666.60966.peg.2119 CDS 1967389 1968672 1 + 1284
FIG00858634: -none- D23_1c2120 Neut_1965 hypothetical protein
fig|6666666.60966.peg.2120 CDS 1968691 1969206 1 + 516 FIG00859317:
-none- D23_1c2121 Neut_1966 hypothetical protein
fig|6666666.60966.peg.2121 CDS 1969209 1969910 3 + 702 InterPro
IPR000179 -none- D23_1c2122 Neut_1967 COGs COG1423
fig|6666666.60966.peg.2122 CDS 1969960 1970334 1 + 375 InterPro
IPR003807 -none- D23_1c2123 Neut_1968 COGs COG2149
fig|6666666.60966.peg.2123 CDS 1971838 1970381 -1 - 1458 Catalase
(EC 1.11.1.6) Oxidative stress; D23_1c2124 Neut_1969
<br>Photorespiration (oxidative C2 cycle);
<br>Protection from Reactive Oxygen Species
fig|6666666.60966.peg.2124 CDS 1973211 1971865 -3 - 1347
FIG00858984: -none- D23_1c2125 Neut_1970 hypothetical protein
fig|6666666.60966.peg.2125 CDS 1974046 1973246 -1 - 801 Protein of
unknown -none- D23_1c2126 Neut_1971 function DUF81
fig|6666666.60966.peg.2126 CDS 1974579 1974124 -3 - 456 Protein of
unknown -none- D23_1c2127 Neut_1972 function DUF55
fig|6666666.60966.peg.2127 CDS 1976514 1974985 -3 - 1530 Capsular
polysaccharide Capsular Polysaccharides D23_1c2128 NA biosynthesis
protein Biosynthesis and WcbQ Assembly fig|6666666.60966.peg.2128
CDS 1977322 1976504 -1 - 819 Oxidoreductase, short- Capsular
Polysaccharides D23_1c2129 Neut_1974 chain Biosynthesis and
dehydrogenase/reductase Assembly family (EC 1.1.1.--)
fig|6666666.60966.peg.2129 CDS 1978801 1977323 -1 - 1479
Glycosyltransferase -none- D23_1c2130 Neut_1975
fig|6666666.60966.peg.2130 CDS 1979888 1978803 -2 - 1086 possible
spore protein -none- D23_1c2131 Neut_1976 [UI:20467420]
fig|6666666.60966.peg.2131 CDS 1981090 1979921 -1 - 1170
FIG00858788: -none- D23_1c2132 Neut_1977 hypothetical protein
fig|6666666.60966.peg.2132 CDS 1982214 1981231 -3 - 984
hypothetical protein -none- D23_1c2133 NA
fig|6666666.60966.peg.2133 CDS 1982778 1982218 -3 - 561
hypothetical protein -none- D23_1c2134 NA
fig|6666666.60966.peg.2134 CDS 1983862 1982783 -1 - 1080
Glycosyltransferase (EC -none- D23_1c2135 Neut_1982 2.4.1.--)
fig|6666666.60966.peg.2135 CDS 1984198 1983896 -1 - 303
hypothetical protein -none- D23_1c2136 Neut_1983
fig|6666666.60966.peg.2136 CDS 1984883 1984704 -2 - 180 Mobile
element protein -none- D23_1c2137 Neut_1984
fig|6666666.60966.peg.2137 CDS 1985076 1984852 -3 - 225
hypothetical protein -none- D23_1c2138 NA
fig|6666666.60966.peg.2139 CDS 1985629 1986384 1 + 756 hypothetical
protein -none- D23_1c2139 Neut_1985 fig|6666666.60966.peg.2140 CDS
1987287 1988645 3 + 1359 FIG00860556: -none- D23_1c2140 Neut_1986
hypothetical protein fig|6666666.60966.peg.2141 CDS 1988761 1989375
1 + 615 Cytochrome oxidase Biogenesis of D23_1c2141 Neut_1987
biogenesis protein cytochrome c oxidases Sco1/SenC/PrrC, putative
copper metallochaperone fig|6666666.60966.peg.2142 CDS 1989381
1990007 3 + 627 FIG00859788: -none- D23_1c2142 Neut_1988
hypothetical protein fig|6666666.60966.peg.2145 CDS 1990866 1990588
-3 - 279 hypothetical membrane -none- D23_1c2144 Neut_1990 protein
fig|6666666.60966.peg.2146 CDS 1991501 1991046 -2 - 456 InterPro
IPR000485 -none- D23_1c2145 Neut_1991 fig|6666666.60966.peg.2147
CDS 1993914 1991785 -3 - 2130 Phosphate Fermentations: Lactate;
D23_1c2146 Neut_1995 acetyltransferase (EC <br>Pyruvate
2.3.1.8) metabolism II: acetyl- CoA, acetogenesis from pyruvate
fig|6666666.60966.peg.2148 CDS 1995278 1994253 -2 - 1026
Fructose-bisphosphate Calvin-Benson cycle; D23_1c2147 Neut_1996
aldolase class I (EC <br>Glycolysis and 4.1.2.13)
Gluconeogenesis fig|6666666.60966.peg.2150 CDS 1995705 1995851 3 +
147 hypothetical protein -none- D23_1c2148 NA
fig|6666666.60966.peg.2152 CDS 1995966 1996298 3 + 333 DNA-binding
protein -none- D23_1c2150 Neut_1998 fig|6666666.60966.peg.2154 CDS
1996639 1996932 1 + 294 protein of unknown -none- D23_1c2151
Neut_1999 function DUF497 fig|6666666.60966.peg.2155 CDS 1996922
1997203 2 + 282 hypothetical protein -none- D23_1c2152 Neut_2000
fig|6666666.60966.peg.2156 CDS 1997890 1998093 1 + 204 Mobile
element protein -none- D23_1c2154 NA fig|6666666.60966.peg.2157 CDS
1998565 1998266 -1 - 300 VapC toxin protein Toxin-antitoxin
replicon D23_1c2155 NA stabilization systems
fig|6666666.60966.peg.2158 CDS 1998899 1998666 -2 - 234 VapB
protein (antitoxin Toxin-antitoxin replicon D23_1c2156 NA to VapC)
stabilization systems fig|6666666.60966.peg.2159 CDS 1999186
1999344 1 + 159 hypothetical protein -none- D23_1c2157 NA
fig|6666666.60966.peg.2160 CDS 1999629 1999339 -3 - 291
transcriptional -none- D23_1c2158 NA regulator, XRE family
fig|6666666.60966.peg.2161 CDS 1999997 1999692 -2 - 306
Phage-related protein -none- D23_1c2159 NA
fig|6666666.60966.peg.2162 CDS 2000147 2000022 -2 - 126
hypothetical protein -none- D23_1c2160 NA
fig|6666666.60966.peg.2163 CDS 2000220 2000486 3 + 267 Mobile
element protein -none- D23_1c2161 NA fig|6666666.60966.peg.2164 CDS
2000507 2000995 2 + 489 Mobile element protein -none- D23_1c2162 NA
fig|6666666.60966.peg.2165 CDS 2001470 2000997 -2 - 474 Mobile
element protein -none- D23_1c2163 Neut_1256
fig|6666666.60966.peg.2166 CDS 2001936 2001544 -3 - 393
hypothetical protein -none- D23_1c2164 Neut_2449
fig|6666666.60966.peg.2167 CDS 2002011 2002328 3 + 318 Mobile
element protein -none- D23_1c2165 NA fig|6666666.60966.peg.2168 CDS
2003529 2002369 -3 - 1161 CDP-4-dehydro-6- -none- D23_1c2166 NA
deoxy-D-glucose 3- dehydratase (EC 4.2.1.--)
fig|6666666.60966.peg.2169 CDS 2004426 2003539 -3 - 888
NAD-dependent CBSS-296591.1.peg.2330 D23_1c2167 NA
epimerase/dehydratase family protein fig|6666666.60966.peg.2170 CDS
2005586 2004468 -2 - 1119 GDP-mannose 4,6- -none- D23_1c2168
Neut_0156 dehydratase (EC 4.2.1.47) fig|6666666.60966.peg.2171 CDS
2007467 2005632 -2 - 1836 hypothetical protein -none- D23_1c2169 NA
fig|6666666.60966.peg.2172 CDS 2010568 2007473 -1 - 3096 Minor
teichoic acid -none- D23_1c2170 NA biosynthesis protein GgaB
fig|6666666.60966.peg.2173 CDS 2012163 2010694 -3 - 1470 InterPro
IPR001173 -none- D23_1c2171 NA COGs COG0463
fig|6666666.60966.peg.2174 CDS 2015828 2012172 -2 - 3657 Beta-1,3-
-none- D23_1c2172 NA glucosyltransferase fig|6666666.60966.peg.2175
CDS 2017307 2016147 -2 - 1161 Capsular polysaccharide Capsular
Polysaccharides D23_1c2173 NA export system inner Biosynthesis and
membrane protein KpsE Assembly fig|6666666.60966.peg.2176 CDS
2017966 2017304 -1 - 663 Capsular polysaccharide Capsular
Polysaccharides D23_1c2174 Neut_0152 ABC transporter, ATP-
Biosynthesis and binding protein KpsT Assembly
fig|6666666.60966.peg.2177 CDS 2018757 2017963 -3 - 795 Capsular
polysaccharide Capsular Polysaccharides D23_1c2175 NA ABC
transporter, Biosynthesis and permease protein KpsM Assembly;
<br>Rhamnose containing glycans fig|6666666.60966.peg.2178
CDS 2019947 2018757 -2 - 1191 Capsular polysaccharide Capsular
Polysaccharides D23_1c2176 Neut_2119 biosynthesis/export
Biosynthesis and periplasmic protein Assembly WcbC
fig|6666666.60966.peg.2179 CDS 2021279 2019957 -2 - 1323 8-amino-7-
Biotin biosynthesis; D23_1c2177 Neut_0461 oxononanoate synthase
<br>Biotin biosynthesis (EC 2.3.1.47) Experimental;
<br>Biotin synthesis cluster fig|6666666.60966.peg.2180 CDS
2025121 2021276 -1 - 3846 Capsular polysaccharide -none- D23_1c2178
NA biosynthesis fatty acid synthase WcbR fig|6666666.60966.peg.2181
CDS 2028811 2025266 -1 - 3546 Capsular polysaccharide -none-
D23_1c2179 Neut_2003 biosynthesis fatty acid synthase WcbR
fig|6666666.60966.peg.2182 CDS 2029053 2029166 3 + 114 hypothetical
protein -none- D23_1c2180 NA fig|6666666.60966.peg.2183 CDS 2029212
2029352 3 + 141 hypothetical protein -none- D23_1c2181 NA
fig|6666666.60966.peg.2184 CDS 2031017 2029434 -2 - 1584
L-aspartate oxidase (EC Mycobacterium D23_1c2182 Neut_2004
1.4.3.16) virulence operon possibly involved in quinolinate
biosynthesis; <br>NAD and NADP cofactor biosynthesis global
fig|6666666.60966.peg.2185 CDS 2031267 2032187 3 + 921
Branched-chain amino Alanine biosynthesis; D23_1c2184 Neut_2005
acid aminotransferase <br>Branched-Chain (EC 2.6.1.42) Amino
Acid Biosynthesis; <br>Leucine Biosynthesis;
<br>Pyruvate Alanine Serine Interconversions
fig|6666666.60966.peg.2186 CDS 2032212 2032421 3 + 210 FIG00858455:
-none- D23_1c2185 Neut_2006 hypothetical protein
fig|6666666.60966.peg.2187 CDS 2032485 2033864 3 + 1380
Phosphomannomutase Mannose Metabolism D23_1c2186 Neut_2007 (EC
5.4.2.8)/ Phosphoglucomutase (EC 5.4.2.2)
fig|6666666.60966.peg.2188 CDS 2033901 2035508 3 + 1608 NAD
synthetase (EC NAD and NADP cofactor D23_1c2187 Neut_2008
6.3.1.5)/Glutamine biosynthesis global; amidotransferase chain
<br>NAD and NADP of NAD synthetase cofactor biosynthesis
global fig|6666666.60966.peg.2189 CDS 2035472 2037178 2 + 1707
Exported zinc -none- D23_1c2188 Neut_2009 metalloprotease YfgC
precursor fig|6666666.60966.peg.2190 CDS 2037257 2038402 2 + 1146
Macrolide-specific Multidrug Resistance D23_1c2189 Neut_2010 efflux
protein MacA Efflux Pumps fig|6666666.60966.peg.2191 CDS 2038413
2039180 3 + 768 Macrolide export ATP- Multidrug Resistance
D23_1c2190 Neut_2011 binding/permease Efflux Pumps protein MacB (EC
3.6.3.--) fig|6666666.60966.peg.2192 CDS 2039177 2040400 2 + 1224
Macrolide export ATP- Multidrug Resistance D23_1c2191 Neut_2012
binding/permease Efflux Pumps protein MacB (EC 3.6.3.--)
fig|6666666.60966.peg.2193 CDS 2040442 2040612 1 + 171 hypothetical
protein -none- D23_1c2192 NA fig|6666666.60966.peg.2195 CDS 2040690
2040875 3 + 186 hypothetical protein -none- D23_1c2193 NA
fig|6666666.60966.peg.2196 CDS 2040926 2042374 2 + 1449 ATP
synthase beta chain -none- D23_1c2194 Neut_2013 (EC 3.6.3.14)
fig|6666666.60966.peg.2197 CDS 2042371 2042781 1 + 411 ATP synthase
epsilon -none- D23_1c2195 Neut_2014 chain (EC 3.6.3.14)
fig|6666666.60966.peg.2198 CDS 2042778 2043059 3 + 282 ATP synthase
protein I -none- D23_1c2196 Neut_2015 fig|6666666.60966.peg.2199
CDS 2043105 2043398 3 + 294 FIG048548: ATP -none- D23_1c2197
Neut_2016 synthase protein I2 fig|6666666.60966.peg.2200 CDS
2043420 2044112 3 + 693 ATP synthase A chain -none- D23_1c2198
Neut_2017 (EC 3.6.3.14) fig|6666666.60966.peg.2201 CDS 2044115
2044393 2 + 279 ATP synthase C chain -none- D23_1c2199 Neut_2018
(EC 3.6.3.14) fig|6666666.60966.peg.2202 CDS 2044400 2045170 2 +
771 ATP synthase B chain -none- D23_1c2200 Neut_2019 (EC 3.6.3.14)
fig|6666666.60966.peg.2203 CDS 2045183 2046733 2 + 1551 ATP
synthase alpha -none- D23_1c2201 Neut_2020 chain (EC 3.6.3.14)
fig|6666666.60966.peg.2204 CDS 2046810 2047607 3 + 798 ATP synthase
gamma -none- D23_1c2202 Neut_2021 chain (EC 3.6.3.14)
fig|6666666.60966.peg.2206 CDS 2048344 2050986 1 + 2643 DNA
mismatch repair DNA repair, bacterial D23_1c2204 Neut_2022 protein
MutS MutL-MutS system; <br>DNA repair system including RecA,
MutS and a hypothetical protein fig|6666666.60966.peg.2207 CDS
2051500 2051021 -1 - 480 FKBP-type peptidyl- G3E family of P-loop
D23_1c2205 Neut_2023 prolyl cis-trans GTPases (metallocenter
isomerase SlyD (EC biosynthesis); 5.2.1.8)
<br>Peptidyl-prolyl cis- trans isomerase; <br>Potassium
homeostasis fig|6666666.60966.peg.2208 CDS 2052207 2051656 -3 - 552
Ribonuclease HII (EC Ribonuclease H; D23_1c2206 Neut_2024 3.1.26.4)
<br>Ribonucleases in Bacillus fig|6666666.60966.peg.2209 CDS
2052737 2052294 -2 - 444 (3R)-hydroxymyristoyl- -none- D23_1c2207
Neut_2025 [acyl carrier protein] dehydratase (EC 4.2.1.--)
fig|6666666.60966.peg.2210 CDS 2053333 2052770 -1 - 564 Outer
membrane Lipopolysaccharide D23_1c2208 Neut_2026 protein H
precursor assembly; <br>Periplasmic Stress Response
fig|6666666.60966.peg.2211 CDS 2055635 2053359 -2 - 2277 Outer
membrane Lipopolysaccharide D23_1c2209 Neut_2027 protein assembly
factor assembly YaeT precursor fig|6666666.60966.peg.2212 CDS
2057020 2055638 -1 - 1383 Membrane-associated -none- D23_1c2210
Neut_2028 zinc metalloprotease fig|6666666.60966.peg.2213 CDS
2058265 2057024 -1 - 1242 1-deoxy-D-xylulose 5-
CBSS-83331.1.peg.3039; D23_1c2211 Neut_2029 phosphate
<br>Isoprenoid reductoisomerase (EC Biosynthesis; 1.1.1.267)
<br>Nonmevalonate Branch of Isoprenoid Biosynthesis
fig|6666666.60966.peg.2214 CDS 2059089 2058262 -3 - 828
Phosphatidate Glycerolipid and D23_1c2212 Neut_2030
cytidylyltransferase (EC Glycerophospholipid 2.7.7.41) Metabolism
in Bacteria fig|6666666.60966.peg.2215 CDS 2059870 2059124 -1 - 747
Undecaprenyl CBSS-83331.1.peg.3039; D23_1c2213 Neut_2031
diphosphate synthase <br>Isoprenoid (EC 2.5.1.31)
Biosynthesis; <br>Isoprenoinds for Quinones;
<br>Polyprenyl Diphosphate Biosynthesis
fig|6666666.60966.peg.2216 CDS 2060476 2059919 -1 - 558 Ribosome
recycling Ribosome recycling D23_1c2214 Neut_2032 factor related
cluster; <br>Translation termination factors bacterial
fig|6666666.60966.peg.2217 CDS 2061239 2060577 -2 - 663 Uridylate
kinase (EC -none- D23_1c2215 Neut_2033 2.7.4.--)
fig|6666666.60966.peg.2218 CDS 2061489 2061361 -3 - 129
hypothetical protein -none- D23_1c2216 NA
fig|6666666.60966.peg.2219 CDS 2062729 2061845 -1 - 885 Translation
elongation CBSS- D23_1c2217 Neut_2034 factor Ts 312309.3.peg.1965;
<br>Ribosome recycling related cluster; <br>Translation
elongation factors bacterial fig|6666666.60966.peg.2220 CDS 2063557
2062802 -1 - 756 SSU ribosomal protein CBSS- D23_1c2218 Neut_2035
S2p (SAe) 312309.3.peg.1965; <br>Ribosome recycling related
cluster fig|6666666.60966.peg.2221 CDS 2064515 2063772 -2 - 744
transcriptional Oxidative stress D23_1c2219 Neut_2036 regulator,
Crp/Fnr family fig|6666666.60966.peg.2222 CDS 2064873 2064562 -3 -
312 Cytochrome c, class I -none- D23_1c2220 Neut_2037
fig|6666666.60966.peg.2223 CDS 2067162 2065111 -3 - 2052
Zinc-regulated outer -none- D23_1c2221 Neut_2038 membrane receptor
fig|6666666.60966.peg.2225 CDS 2067907 2068395 1 + 489 Zinc uptake
regulation Glycyl-tRNA synthetase D23_1c2222 NA protein ZUR
containing cluster; <br>Oxidative stress; <br>Zinc
regulated enzymes fig|6666666.60966.peg.2226 CDS 2068438 2068560 1
+ 123 Mobile element protein -none- D23_1c2223 Neut_0884
fig|6666666.60966.peg.2228 CDS 2068811 2069020 2 + 210 hypothetical
protein -none- D23_1c2224 NA fig|6666666.60966.peg.2231 CDS 2069466
2069332 -3 - 135 hypothetical protein -none- D23_1c2225 NA
fig|6666666.60966.peg.2232 CDS 2069455 2070327 1 + 873 COG0613,
Predicted A cluster relating to D23_1c2226 Neut_2039
metal-dependent Tryptophanyl-tRNA phosphoesterases (PHP synthetase;
<br>tRNA family) modification Bacteria
fig|6666666.60966.peg.2233 CDS 2070450 2071082 3 + 633 YciO family
-none- D23_1c2227 Neut_2040 fig|6666666.60966.peg.2234 CDS 2071075
2071740 1 + 666 FIG004556: membrane A cluster relating to
D23_1c2228 Neut_2041 metalloprotease Tryptophanyl-tRNA synthetase
fig|6666666.60966.peg.2235 CDS 2071817 2073019 2 + 1203
Tryptophanyl-tRNA A cluster relating to D23_1c2229 Neut_2042
synthetase (EC 6.1.1.2) Tryptophanyl-tRNA synthetase;
<br>tRNA aminoacylation, Trp fig|6666666.60966.peg.2236 CDS
2073064 2073864 1 + 801 Segregation and -none- D23_1c2230 Neut_2043
condensation protein A fig|6666666.60966.peg.2237 CDS 2073830
2074480 2 + 651 Segregation and -none- D23_1c2231 Neut_2044
condensation protein B fig|6666666.60966.peg.2238 CDS 2074504
2075751 1 + 1248 Isocitrate 5-FCL-like protein; D23_1c2232
Neut_2045 dehydrogenase [NADP] <br>TCA Cycle (EC 1.1.1.42)
fig|6666666.60966.peg.2239 CDS 2076095 2075892 -2 - 204 Cold shock
protein CspD Cold shock, CspA family D23_1c2233 Neut_2046 of
proteins fig|6666666.60966.peg.2240 CDS 2076577 2076407 -1 - 171
hypothetical protein -none- D23_1c2234 NA
fig|6666666.60966.peg.2241 CDS 2076576 2076779 3 + 204
ATP-dependent Clp ClpAS cluster; D23_1c2235 Neut_2047 protease
adaptor <br>Proteolysis in protein ClpS bacteria,
ATP-dependent fig|6666666.60966.peg.2242 CDS 2076781 2079051 1 +
2271 ATP-dependent Clp ClpAS cluster; D23_1c2236 Neut_2048 protease
ATP-binding <br>Proteolysis in subunit ClpA bacteria, ATP-
dependent; <br>Ribosome recycling related cluster
fig|6666666.60966.peg.2243 CDS 2079170 2080129 2 + 960 TRAP
transporter solute TRAP Transporter D23_1c2237 Neut_2049 receptor,
unknown unknown substrate 6 substrate 6 fig|6666666.60966.peg.2244
CDS 2080157 2080885 2 + 729 Orotate De Novo Pyrimidine D23_1c2238
Neut_2050 phosphoribosyltransferase Synthesis (EC 2.4.2.10)
fig|6666666.60966.peg.2245 CDS 2081203 2082156 1 + 954 COGs COG0715
-none- D23_1c2239 Neut_2051 fig|6666666.60966.peg.2246 CDS 2082161
2082997 2 + 837 Alkanesulfonates Alkanesulfonate D23_1c2240
Neut_2052 transport system assimilation permease protein
fig|6666666.60966.peg.2247 CDS 2083232 2083038 -2 - 195
hypothetical protein -none- D23_1c2241 NA
fig|6666666.60966.peg.2248 CDS 2083287 2083823 3 + 537 ABC-type
Alkanesulfonate D23_1c2242 Neut_2053 nitrate/sulfonate/bicarbonate
assimilation transport system, ATPase component
fig|6666666.60966.peg.2249 CDS 2083938 2086493 3 + 2556 Glycogen
Glycogen metabolism D23_1c2243 Neut_2054 phosphorylase (EC 2.4.1.1)
fig|6666666.60966.peg.2251 CDS 2086807 2086661 -1 - 147
hypothetical protein -none- D23_1c2244 NA
fig|6666666.60966.peg.2252 CDS 2086806 2087288 3 + 483 Flagellar
biosynthesis Flagellum D23_1c2245 Neut_2055 protein FliL
fig|6666666.60966.peg.2253 CDS 2087301 2088293 3 + 993 Flagellar
motor switch Flagellar motility; D23_1c2246 Neut_2056 protein FliM
<br>Flagellum fig|6666666.60966.peg.2254 CDS 2088322 2088795
1 + 474 Flagellar motor switch Flagellar motility; D23_1c2247
Neut_2057 protein FliN <br>Flagellum
fig|6666666.60966.peg.2255 CDS 2088822 2089265 3 + 444 Flagellar
biosynthesis Flagellum D23_1c2248 Neut_2058 protein FliQ
fig|6666666.60966.peg.2256 CDS 2089255 2090040 1 + 786 Flagellar
biosynthesis Flagellum D23_1c2249 Neut_2059 protein FliP
fig|6666666.60966.peg.2257 CDS 2090056 2090331 1 + 276 Flagellar
biosynthesis Flagellum D23_1c2250 Neut_2060 protein FliQ
fig|6666666.60966.peg.2258 CDS 2090429 2091229 2 + 801 Flagellar
biosynthesis Flagellar motility; D23_1c2251 Neut_2061 protein FliR
<br>Flagellum fig|6666666.60966.peg.2259 CDS 2091389 2093485
2 + 2097 FIG00858519: -none- D23_1c2252 Neut_2062 hypothetical
protein fig|6666666.60966.peg.2260 CDS 2093591 2095027 2 + 1437
FIG00858578: -none- D23_1c2253 Neut_2063 hypothetical protein
fig|6666666.60966.peg.2261 CDS 2096049 2095090 -3 - 960 alpha/beta
hydrolase -none- D23_1c2254 Neut_2064 fold
fig|6666666.60966.peg.2262 CDS 2096035 2096187 1 + 153 hypothetical
protein -none- D23_1c2255 NA fig|6666666.60966.peg.2263 CDS 2097510
2096296 -3 - 1215 Argininosuccinate Arginine Biosynthesis--
D23_1c2256 Neut_2065 synthase (EC 6.3.4.5) gjo; <br>Arginine
Biosynthesis extended
fig|6666666.60966.peg.2264 CDS 2098473 2097550 -3 - 924 Ornithine
Arginine Biosynthesis-- D23_1c2257 Neut_2066 carbamoyltransferase
gjo; <br>Arginine (EC 2.1.3.3) Biosynthesis extended;
<br>Arginine and Ornithine Degradation
fig|6666666.60966.peg.2266 CDS 2099808 2099680 -3 - 129
hypothetical protein -none- D23_1c2259 Neut_2067
fig|6666666.60966.peg.2265 CDS 2099605 2098649 -1 - 957
Acetylornithine Arginine Biosynthesis-- D23_1c2259 Neut_2067
aminotransferase (EC gjo; <br>Arginine 2.6.1.11) Biosynthesis
extended fig|6666666.60966.peg.2267 CDS 2100416 2100066 -2 - 351
FIG00858925: -none- D23_1c2260 Neut_2068 hypothetical protein
fig|6666666.60966.peg.2268 CDS 2100762 2100517 -3 - 246
FIG00859242: -none- D23_1c2261 Neut_2069 hypothetical protein
fig|6666666.60966.peg.2269 CDS 2102838 2100763 -3 - 2076
FIG00858999: -none- D23_1c2262 Neut_2070 hypothetical protein
fig|6666666.60966.peg.2270 CDS 2103683 2102844 -2 - 840 Cysteine
synthase B (EC Cysteine Biosynthesis D23_1c2263 Neut_2071 2.5.1.47)
fig|6666666.60966.peg.2272 CDS 2106646 2103854 -1 - 2793
FIG00860005: -none- D23_1c2264 Neut_2072 hypothetical protein
fig|6666666.60966.peg.2274 CDS 2109519 2108932 -3 - 588
hypothetical protein -none- D23_1c2268 Neut_2074
fig|6666666.60966.peg.2275 CDS 2110331 2109591 -2 - 741 putative
(U92432) ORF4 -none- D23_1c2269 Neut_2316 (Nitrosospira sp. NpAV)
fig|6666666.60966.peg.2276 CDS 2111663 2110398 -2 - 1266
Particulate methane Particulate methane D23_1c2270 Neut_2317
monooxygenase B- monooxygenase subunit (EC 1.14.13.25) (pMMO)
fig|6666666.60966.peg.2277 CDS 2112493 2111663 -1 - 831 Particulate
methane Particulate methane D23_1c2271 Neut_2318 monooxygenase A-
monooxygenase subunit (EC 1.14.13.25) (pMMO)
fig|6666666.60966.peg.2278 CDS 2113482 2112667 -3 - 816 Particulate
methane Particulate methane D23_1c2272 Neut_2319 monooxygenase C-
monooxygenase subunit (EC 1.14.13.25) (pMMO)
fig|6666666.60966.peg.2279 CDS 2114624 2114052 -2 - 573
CDP-diacylglycerol-- Glycerolipid and D23_1c2273 Neut_2079
glycerol-3-phosphate 3- Glycerophospholipid phosphatidyltransferase
Metabolism in Bacteria (EC 2.7.8.5) fig|6666666.60966.peg.2280 CDS
2116254 2114755 -3 - 1500 Glycerol kinase (EC Glycerol and
Glycerol-3- D23_1c2274 Neut_2080 2.7.1.30) phosphate Uptake and
Utilization; <br>Glycerolipid and Glycerophospholipid
Metabolism in Bacteria fig|6666666.60966.peg.2281 CDS 2116718
2116305 -2 - 414 Regulator of nucleoside Transcription factors
D23_1c2275 Neut_2081 diphosphate kinase bacterial
fig|6666666.60966.peg.2282 CDS 2116748 2116897 2 + 150 hypothetical
protein -none- D23_1c2276 NA fig|6666666.60966.peg.2283 CDS 2117727
2117005 -3 - 723 Phosphate regulon High affinity phosphate
D23_1c2277 Neut_2082 transcriptional transporter and control
regulatory protein PhoB of PHO regulon; (SphR) <br>PhoR-PhoB
two- component regulatory system; <br>Phosphate metabolism
fig|6666666.60966.peg.2284 CDS 2119187 2118225 -2 - 963 Mobile
element protein -none- D23_1c2278 Neut_1746
fig|6666666.60966.peg.2287 CDS 2121603 2120356 -3 - 1248
Aspartokinase (EC CBSS-216591.1.peg.168; D23_1c2282 Neut_2084
2.7.2.4) <br>Lysine Biosynthesis DAP Pathway, GJO scratch;
<br>Threonine and Homoserine Biosynthesis
fig|6666666.60966.peg.2288 CDS 2122439 2121855 -2 - 585 Putative
peptidoglycan -none- D23_1c2283 Neut_2085 binding domain 1
fig|6666666.60966.peg.2289 CDS 2122914 2124089 3 + 1176 Acetate
kinase (EC Fermentations: Lactate; D23_1c2284 Neut_2086 2.7.2.1)
<br>Pyruvate metabolism II: acetyl- CoA, acetogenesis from
pyruvate fig|6666666.60966.peg.2290 CDS 2124134 2126509 2 + 2376
Xylulose-5-phosphate Fermentations: Lactate; D23_1c2285 Neut_2087
phosphoketolase (EC <br>Fermentations: 4.1.2.9); Fructose-6-
Lactate; <br>Pentose phosphate phosphate pathway;
phosphoketolase (EC <br>Pentose phosphate 4.1.2.22) pathway
fig|6666666.60966.peg.2291 CDS 2126813 2126977 2 + 165 hypothetical
protein -none- D23_1c2287 NA fig|6666666.60966.peg.2292 CDS 2128152
2127058 -3 - 1095 Transaldolase (EC Pentose phosphate D23_1c2288
Neut_2089 2.2.1.2) pathway fig|6666666.60966.peg.2293 CDS 2128367
2128218 -2 - 150 hypothetical protein -none- D23_1c2289 NA
fig|6666666.60966.peg.2294 CDS 2128351 2128908 1 + 558 FIG006045:
Sigma Iron siderophore sensor D23_1c2290 Neut_2090 factor, ECF
subfamily & receptor system fig|6666666.60966.peg.2295 CDS
2128915 2129877 1 + 963 Iron siderophore sensor Iron siderophore
sensor D23_1c2291 Neut_2091 protein & receptor system
fig|6666666.60966.peg.2296 CDS 2129956 2132253 1 + 2298
TonB-dependent Ton and Tol transport D23_1c2292 Neut_2092 receptor
systems fig|6666666.60966.peg.2297 CDS 2132801 2132271 -2 - 531
FIG00858714: -none- D23_1c2293 Neut_2093 hypothetical protein
fig|6666666.60966.peg.2298 CDS 2133157 2132813 -1 - 345
FIG00858447: -none- D23_1c2294 Neut_2094 hypothetical protein
fig|6666666.60966.peg.2299 CDS 2134515 2133133 -3 - 1383 Xaa-Pro
Aminopeptidases (EC D23_1c2295 Neut_2095 aminopeptidase (EC
3.4.11.--); <br>CBSS- 3.4.11.9) 87626.3.peg.3639
fig|6666666.60966.peg.2301 CDS 2134633 2135313 1 + 681
Ribulose-phosphate 3- Calvin-Benson cycle; D23_1c2296 Neut_2096
epimerase (EC 5.1.3.1) <br>Pentose phosphate pathway;
<br>Riboflavin synthesis cluster fig|6666666.60966.peg.2302
CDS 2135328 2136050 3 + 723 Phosphoglycolate 2-phosphoglycolate
D23_1c2297 Neut_2097 phosphatase (EC salvage; <br>Glycolate,
3.1.3.18) glyoxylate interconversions; <br>Photorespiration
(oxidative C2 cycle) fig|6666666.60966.peg.2303 CDS 2136160 2137647
1 + 1488 Anthranilate synthase, Chorismate: D23_1c2298 Neut_2098
aminase component (EC Intermediate for 4.1.3.27) synthesis of
Tryptophan, PAPA antibiotics, PABA, 3-hydroxyanthranilate and
more.; <br>Tryptophan synthesis fig|6666666.60966.peg.2304
CDS 2138110 2137682 -1 - 429 Ferredoxin reductase Anaerobic
respiratory D23_1c2299 Neut_2099 reductases
fig|6666666.60966.peg.2305 CDS 2138482 2138138 -1 - 345
FIG00858997: -none- D23_1c2300 Neut_2100 hypothetical protein
fig|6666666.60966.peg.2306 CDS 2138586 2139236 3 + 651 Iron-sulfur
cluster CBSS-196164.1.peg.1690 D23_1c2301 Neut_2101 regulator SufR
fig|6666666.60966.peg.2307 CDS 2139353 2140534 2 + 1182
FIG00859085: -none- D23_1c2302 Neut_2102 hypothetical protein
fig|6666666.60966.peg.2308 CDS 2142375 2140606 -3 - 1770
Dihydrolipoamide Pyruvate metabolism II: D23_1c2304 Neut_2103
dehydrogenase of acetyl-CoA, acetogenesis pyruvate from pyruvate;
<br>TCA dehydrogenase Cycle complex (EC 1.8.1.4)
fig|6666666.60966.peg.2309 CDS 2143648 2142380 -1 - 1269
Gamma-glutamyl Proline Synthesis D23_1c2305 Neut_2104 phosphate
reductase (EC 1.2.1.41) fig|6666666.60966.peg.2310 CDS 2144399
2143713 -2 - 687 InterPro IPR001440 -none- D23_1c2306 Neut_2105
COGs COG0457 fig|6666666.60966.peg.2311 CDS 2145656 2144412 -2 -
1245 TPR/glycosyl -none- D23_1c2307 Neut_2106 transferase domain
protein fig|6666666.60966.peg.2312 CDS 2146522 2145650 -1 - 873
Esterase/lipase/thioesterase -none- D23_1c2308 Neut_2107 family
active site fig|6666666.60966.peg.2313 CDS 2147373 2146519 -3 - 855
Esterase/lipase/thioesterase -none- D23_1c2309 Neut_2108 family
active site fig|6666666.60966.peg.2314 CDS 2147631 2147380 -3 - 252
FIG00858580: -none- D23_1c2310 Neut_2109 hypothetical protein
fig|6666666.60966.peg.2315 CDS 2147817 2149007 3 + 1191
Tetraacyldisaccharide Broadly distributed D23_1c2311 Neut_2110
4'-kinase (EC proteins not in 2.7.1.130)/FIG002473: subsystems;
<br>KDO2- Protein YcaR in KDO2- Lipid A biosynthesis Lipid A
biosynthesis cluster 2; <br>KDO2- cluster Lipid A
biosynthesis cluster 2 fig|6666666.60966.peg.2316 CDS 2149225
2149353 1 + 129 hypothetical protein -none- D23_1c2312 NA
fig|6666666.60966.peg.2318 CDS 2150705 2149527 -2 - 1179 Lipid
carrier: UDP-N- CBSS- D23_1c2313 Neut_2112
acetylgalactosaminyltransferase 296591.1.peg.2330; (EC 2.4.1.--)/
<br>CBSS- Alpha-1,3-N- 296591.1.peg.2330; acetylgalactosamine
<br>CBSS- transferase PglA (EC 296591.1.peg.2330; 2.4.1.--);
Putative <br>N-linked glycosyltransferase Glycosylation in
Bacteria; <br>N-linked Glycosylation in Bacteria
fig|6666666.60966.peg.2319 CDS 2151819 2150689 -3 - 1131 Glycosyl
transferase, -none- D23_1c2314 Neut_2113 group 1 family protein
fig|6666666.60966.peg.2320 CDS 2153132 2151816 -2 - 1317
hypothetical protein -none- D23_1c2315 NA
fig|6666666.60966.peg.2321 CDS 2154290 2153199 -2 - 1092
Alpha-1,4-N- N-linked Glycosylation in D23_1c2316 Neut_2115
acetylgalactosamine Bacteria transferase PglJ (EC 2.4.1.--)
fig|6666666.60966.peg.2322 CDS 2155270 2154290 -1 - 981 COGs
COG0439 -none- D23_1c2317 Neut_2116 fig|6666666.60966.peg.2323 CDS
2156578 2155337 -1 - 1242 Membrane protein -none- D23_1c2318
Neut_2117 involved in the export of O-antigen, teichoic acid
lipoteichoic acids fig|6666666.60966.peg.2324 CDS 2156818 2157207 1
+ 390 Low molecular weight Capsular Polysaccharides D23_1c2319
Neut_2118 protein-tyrosine- Biosynthesis and phosphatase Wzb (EC
Assembly 3.1.3.48) fig|6666666.60966.peg.2325 CDS 2157230 2158477 2
+ 1248 Capsule polysaccharide -none- D23_1c2320 Neut_2119 export
protein fig|6666666.60966.peg.2326 CDS 2158531 2160774 1 + 2244
Tyrosine-protein kinase Capsular Polysaccharides D23_1c2321
Neut_2120 Wzc (EC 2.7.10.2) Biosynthesis and Assembly
fig|6666666.60966.peg.2327 CDS 2160771 2162330 3 + 1560
Undecaprenyl- -none- D23_1c2322 Neut_2121 phosphate N-
acetylglucosaminyl 1- phosphate transferase (EC 2.7.8.--)
fig|6666666.60966.peg.2329 CDS 2165972 2162400 -2 - 3573 Chromosome
partition DNA structural proteins, D23_1c2323 Neut_2122 protein smc
bacterial fig|6666666.60966.peg.2330 CDS 2166059 2166478 2 + 420
NADPH-dependent 7- -none- D23_1c2324 Neut_2123 cyano-7-deazaguanine
reductase (EC 1.7.1.13) fig|6666666.60966.peg.2331 CDS 2166527
2167927 2 + 1401 Fumarate hydratase TCA Cycle D23_1c2325 Neut_2124
class II (EC 4.2.1.2) fig|6666666.60966.peg.2332 CDS 2168192
2168052 -2 - 141 hypothetical protein -none- D23_1c2326 NA
fig|6666666.60966.peg.2333 CDS 2168473 2168640 1 + 168 hypothetical
protein -none- D23_1c2327 NA fig|6666666.60966.peg.2334 CDS 2168888
2169181 2 + 294 Mobile element protein -none- D23_1c2328
Neut_1719
fig|6666666.60966.peg.2335 CDS 2169280 2170158 1 + 879 Mobile
element protein -none- D23_1c2329 Neut_1720
fig|6666666.60966.peg.2337 CDS 2171884 2170655 -1 - 1230
diguanylate -none- D23_1c2332 Neut_2126 phosphodiesterase
fig|6666666.60966.peg.2338 CDS 2172707 2171898 -2 - 810 Putative
diheme Soluble cytochromes D23_1c2333 Neut_2127 cytochrome c-553
and functionally related electron carriers
fig|6666666.60966.peg.2339 CDS 2172852 2172977 3 + 126 hypothetical
protein -none- D23_1c2334 NA fig|6666666.60966.peg.2340 CDS 2175331
2172950 -1 - 2382 Type II secretory -none- D23_1c2335 Neut_2128
pathway, ATPase PulE/Tfp pilus assembly pathway, ATPase PilB
fig|6666666.60966.peg.2341 CDS 2176108 2175344 -1 - 765 CAMP cAMP
signaling in D23_1c2336 Neut_2129 phosphodiesterases bacteria
class-II:Metallo-beta- lactamase superfamily
fig|6666666.60966.peg.2342 CDS 2176622 2176197 -2 - 426 Universal
stress protein -none- D23_1c2337 Neut_2130 (Usp)
fig|6666666.60966.peg.2343 CDS 2177459 2176734 -2 - 726 Membrane
protein -none- D23_1c2338 Neut_2131 TerC, possibly involved in
tellurium resistance fig|6666666.60966.peg.2344 CDS 2178586 2177462
-1 - 1125 Patatin -none- D23_1c2339 Neut_2132
fig|6666666.60966.peg.2345 CDS 2178900 2179850 3 + 951 Proline
iminopeptidase Proline, 4- D23_1c2340 Neut_2133 (EC 3.4.11.5)
hydroxyproline uptake and utilization fig|6666666.60966.peg.2346
CDS 2180553 2179870 -3 - 684 Dethiobiotin synthetase Biotin
biosynthesis; D23_1c2341 Neut_2134 (EC 6.3.3.3) <br>Biotin
biosynthesis Experimental; <br>Biotin synthesis cluster
fig|6666666.60966.peg.2347 CDS 2181452 2180556 -2 - 897 Biotin
synthesis protein Biotin biosynthesis; D23_1c2342 Neut_2135 BioC
<br>Biotin biosynthesis Experimental; <br>Biotin
synthesis cluster fig|6666666.60966.peg.2348 CDS 2182200 2181442 -3
- 759 Biotin synthesis protein Biotin biosynthesis; D23_1c2343
Neut_2136 BioH <br>Biotin biosynthesis Experimental;
<br>Biotin synthesis cluster fig|6666666.60966.peg.2349 CDS
2183365 2182202 -1 - 1164 8-amino-7- Biotin biosynthesis;
D23_1c2344 Neut_2137 oxononanoate synthase <br>Biotin
biosynthesis (EC 2.3.1.47) Experimental; <br>Biotin synthesis
cluster fig|6666666.60966.peg.2350 CDS 2184393 2183371 -3 - 1023
Biotin synthase (EC Biotin biosynthesis; D23_1c2345 Neut_2138
2.8.1.6) <br>Biotin biosynthesis Experimental;
<br>Biotin synthesis cluster fig|6666666.60966.peg.2351 CDS
2184641 2184453 -2 - 189 hypothetical protein -none- D23_1c2346 NA
fig|6666666.60966.peg.2352 CDS 2184698 2185168 2 + 471 Competence
protein F Biotin biosynthesis D23_1c2347 Neut_2139 homolog,
Experimental; <br>Biotin phosphoribosyltransferase synthesis
cluster; domain; protein <br>CBSS- YhgH required for
216591.1.peg.168 utilization of DNA as sole source of carbon and
energy fig|6666666.60966.peg.2353 CDS 2185222 2185686 1 + 465 tRNA
(cytidine(34)- Biotin synthesis cluster; D23_1c2348 Neut_2140
2'-O)- <br>RNA methylation methyltransferase (EC 2.1.1.207)
## TrmL fig|6666666.60966.peg.2354 CDS 2185773 2186303 3 + 531
protein of unknown -none- D23_1c2349 Neut_2141 function DUF1130
fig|6666666.60966.peg.2355 CDS 2186489 2187325 2 + 837
SAM-dependent -none- D23_1c2350 Neut_2142 methyltransferase (EC
2.1.1.--) fig|6666666.60966.peg.2356 CDS 2189013 2187523 -3 - 1491
Glucose-6-phosphate 1- Pentose phosphate D23_1c2351 Neut_2143
dehydrogenase (EC pathway 1.1.1.49) fig|6666666.60966.peg.2357 CDS
2189925 2189017 -3 - 909 6-phosphogluconate D-gluconate and
D23_1c2352 Neut_2144 dehydrogenase, ketogluconates decarboxylating
(EC metabolism; 1.1.1.44) <br>Pentose phosphate pathway
fig|6666666.60966.peg.2358 CDS 2191152 2189995 -3 - 1158 COGs
COG1397 -none- D23_1c2353 Neut_2145 fig|6666666.60966.peg.2359 CDS
2191494 2191195 -3 - 300 UPF0235 protein CBSS-630.2.peg.3360
D23_1c2354 Neut_2146 VC0458 fig|6666666.60966.peg.2360 CDS 2192054
2191494 -2 - 561 Integral membrane CBSS-630.2.peg.3360 D23_1c2355
Neut_2147 protein YggT, involved in response to extracytoplasmic
stress (osmotic shock) fig|6666666.60966.peg.2361 CDS 2192939
2192127 -2 - 813 Pyrroline-5-carboxylate A Hypothetical Protein
D23_1c2356 Neut_2148 reductase (EC 1.5.1.2) Related to Proline
Metabolism; <br>CBSS- 630.2.peg.3360; <br>Proline
Synthesis fig|6666666.60966.peg.2362 CDS 2193210 2193019 -3 - 192
FIG00859708: -none- D23_1c2357 Neut_2149 hypothetical protein
fig|6666666.60966.peg.2364 CDS 2194302 2194580 3 + 279 Ribonuclease
P protein Cell Division Subsystem D23_1c2359 Neut_2152 component
(EC including YidCD; 3.1.26.5) <br>RNA modification cluster;
<br>tRNA processing fig|6666666.60966.peg.2365 CDS 2194877
2196745 2 + 1869 Inner membrane CTP synthase (EC D23_1c2360
Neut_2154 protein translocase 6.3.4.2) cluster; <br>Cell
component YidC, long Division Subsystem form including YidCD;
<br>RNA modification cluster fig|6666666.60966.peg.2366 CDS
2196792 2198171 3 + 1380 GTPase and tRNA-U34 Cell Division
Subsystem D23_1c2361 Neut_2155 5-formylation enzyme including
YidCD; TrmE <br>RNA modification and chromosome partitioning
cluster; <br>RNA modification cluster; <br>Universal
GTPases; <br>mnm5U34 biosynthesis bacteria; <br>tRNA
modification Bacteria fig|6666666.60966.peg.2367 CDS 2198398
2198667 1 + 270 SSU ribosomal protein -none- D23_1c2363 Neut_2156
S15p (S13e) fig|6666666.60966.peg.2368 CDS 2198846 2200963 2 + 2118
Polyribonucleotide Bacterial RNA- D23_1c2364 Neut_2157
nucleotidyltransferase metabolizing Zn- (EC 2.7.7.8) dependent
hydrolases; <br>Polyadenylation bacterial
fig|6666666.60966.peg.2369 CDS 2201167 2201039 -1 - 129
hypothetical protein -none- D23_1c2365 NA
fig|6666666.60966.peg.2371 CDS 2201553 2202926 3 + 1374 RND efflux
system, Multidrug Resistance D23_1c2367 Neut_2158 outer membrane
Efflux Pumps lipoprotein CmeC fig|6666666.60966.peg.2372 CDS
2203015 2204220 1 + 1206 Membrane fusion Multidrug Resistance
D23_1c2368 Neut_2159 protein of RND family Efflux Pumps multidrug
efflux pump fig|6666666.60966.peg.2373 CDS 2204238 2207432 3 + 3195
RND efflux system, Multidrug Resistance D23_1c2369 Neut_2160 inner
membrane Efflux Pumps transporter CmeB fig|6666666.60966.peg.2375
CDS 2208043 2207702 -1 - 342 hypothetical protein -none- D23_1c2370
Neut_2161 fig|6666666.60966.peg.2376 CDS 2208812 2208072 -2 - 741
conserved hypothetical -none- D23_1c2371 Neut_2162 protein
[Pyrococcus horikoshii]; COG2102: Predicted ATPases of PP-loop
superfamily; IPR002761: Domain of unknown function DUF71
fig|6666666.60966.peg.2377 CDS 2209043 2208924 -2 - 120
FIG00859479: -none- D23_1c2372 Neut_2163 hypothetical protein
fig|6666666.60966.peg.2379 CDS 2210878 2209472 -1 - 1407
GTP-binding protein CBSS- D23_1c2374 Neut_2164 EngA
290633.1.peg.1906; <br>CBSS- 498211.3.peg.1415;
<br>Universal GTPases fig|6666666.60966.peg.2380 CDS 2212159
2210930 -1 - 1230 Outer membrane CBSS- D23_1c2375 Neut_2165 protein
YfgL, lipoprotein 290633.1.peg.1906; component of the
<br>CBSS- protein assembly 498211.3.peg.1415; complex (forms
a <br>Lipopolysaccharide complex with YaeT, assembly YfiO,
and NlpB) fig|6666666.60966.peg.2381 CDS 2212800 2212162 -3 - 639
Mlr7403 protein CBSS- D23_1c2376 Neut_2166 290633.1.peg.1906;
<br>CBSS- 498211.3.peg.1415 fig|6666666.60966.peg.2382 CDS
2214088 2212823 -1 - 1266 Histidyl-tRNA CBSS- D23_1c2377 Neut_2167
synthetase (EC 6.1.1.21) 498211.3.peg.1415; <br>tRNA
aminoacylation, His fig|6666666.60966.peg.2383 CDS 2215286 2214081
-2 - 1206 1-hydroxy-2-methyl-2- CBSS- D23_1c2378 Neut_2168
(E)-butenyl 4- 498211.3.peg.1415; diphosphate synthase
<br>CBSS- (EC 1.17.7.1) 83331.1.peg.3039;
<br>Isoprenoid Biosynthesis; <br>Nonmevalonate Branch
of Isoprenoid Biosynthesis fig|6666666.60966.peg.2384 CDS 2216438
2215359 -2 - 1080 FIG021952: putative CBSS-498211.3.peg.1415
D23_1c2379 Neut_2169 membrane protein fig|6666666.60966.peg.2385
CDS 2217306 2216428 -3 - 879 Type IV pilus biogenesis
CBSS-498211.3.peg.1415 D23_1c2380 Neut_2170 protein PilF
fig|6666666.60966.peg.2386 CDS 2218414 2217275 -1 - 1140 Ribosomal
RNA large CBSS- D23_1c2381 Neut_2171 subunit 498211.3.peg.1415;
methyltransferase N (EC <br>RNA methylation 2.1.1.--)
fig|6666666.60966.peg.2387 CDS 2218877 2218452 -2 - 426 Nucleoside
diphosphate CBSS- D23_1c2382 Neut_2172 kinase (EC 2.7.4.6)
498211.3.peg.1415; <br>Purine conversions;
<br>pyrimidine conversions fig|6666666.60966.peg.2389 CDS
2219591 2219175 -2 - 417 Chain A, Red Copper -none- D23_1c2383
Neut_2173 Protein Nitrosocyanin fig|6666666.60966.peg.2390 CDS
2220042 2221430 3 + 1389 Aminotransferase Hopanes D23_1c2384
Neut_2174 HpnO, required for aminobacteriohopanetriol
fig|6666666.60966.peg.2391 CDS 2222146 2221442 -1 - 705 DNA
polymerase III CBSS-228410.1.peg.134; D23_1c2385 Neut_2175 epsilon
subunit (EC <br>CBSS- 2.7.7.7) 342610.3.peg.1536
fig|6666666.60966.peg.2392 CDS 2222646 2222158 -3 - 489
Ribonuclease HI (EC CBSS-228410.1.peg.134; D23_1c2386 Neut_2176
3.1.26.4) <br>CBSS- 342610.3.peg.1536; <br>Ribonuclease
H fig|6666666.60966.peg.2393 CDS 2223440 2222706 -2 - 735
FIG005121: SAM- CBSS-228410.1.peg.134; D23_1c2387 Neut_2177
dependent <br>CBSS- methyltransferase (EC 342610.3.peg.1536;
2.1.1.--) <br>Glutathione: Non- redox reactions
fig|6666666.60966.peg.2394 CDS 2223500 2224267 2 + 768
Hydroxyacylglutathione CBSS-228410.1.peg.134; D23_1c2388 Neut_2178
hydrolase (EC 3.1.2.6) <br>CBSS- 342610.3.peg.1536;
<br>Glutathione: Non- redox reactions;
<br>Methylglyoxal Metabolism fig|6666666.60966.peg.2396 CDS
2225143 2224571 -1 - 573 hypothetical protein -none- D23_1c2389
Neut_2179 fig|6666666.60966.peg.2397 CDS 2225287 2225162 -1 - 126
hypothetical protein -none- D23_1c2390 NA
fig|6666666.60966.peg.2398 CDS 2226167 2225250 -2 - 918
hypothetical protein -none- D23_1c2391 Neut_2180
fig|6666666.60966.peg.2399 CDS 2228864 2226171 -2 - 2694 Helicase,
SNF2/RAD54 -none- D23_1c2392 Neut_2181 family
fig|6666666.60966.peg.2401 CDS 2229650 2229480 -2 - 171
hypothetical protein -none- D23_1c2393 NA
fig|6666666.60966.peg.2402 CDS 2229693 2230814 3 + 1122
Oxidoreductase, FMN- -none- D23_1c2394 Neut_2182 binding
fig|6666666.60966.peg.2403 CDS 2230925 2231368 2 + 444 Ornithine
Arginine and Ornithine D23_1c2395 Neut_2183 cyclodeaminase (EC
Degradation 4.3.1.12) fig|6666666.60966.peg.2404 CDS 2231434
2233005 1 + 1572 Phosphoglucomutase -none- D23_1c2396 Neut_2184 (EC
5.4.2.2) fig|6666666.60966.peg.2405 CDS 2233192 2233344 1 + 153
hypothetical protein -none- D23_1c2397 NA
fig|6666666.60966.peg.2406 CDS 2234195 2233347 -2 - 849 Mobile
element protein -none- D23_1c2398 Neut_1888
fig|6666666.60966.peg.2407 CDS 2234437 2234252 -1 - 186 Mobile
element protein -none- D23_1c2399 Neut_2500
fig|6666666.60966.peg.2408 CDS 2234636 2235049 2 + 414
Cobalt-zinc-cadmium Cobalt-zinc-cadmium D23_1c2400 Neut_2185
resistance protein resistance fig|6666666.60966.peg.2409 CDS
2235949 2235359 -1 - 591 Hydroxyacylglutathione
CBSS-228410.1.peg.134; D23_1c2401 Neut_2178 hydrolase (EC 3.1.2.6)
<br>CBSS- 342610.3.peg.1536; <br>Glutathione: Non-
redox reactions; <br>Methylglyoxal Metabolism
fig|6666666.60966.peg.2410 CDS 2236135 2236287 1 + 153 hypothetical
protein -none- D23_1c2403 Neut_1255 fig|6666666.60966.peg.2411 CDS
2236295 2236462 2 + 168 hypothetical protein -none- D23_1c2404
Neut_2449 fig|6666666.60966.peg.2412 CDS 2236616 2236419 -2 - 198
Mobile element protein -none- D23_1c2405 Neut_2268
fig|6666666.60966.peg.2414 CDS 2236758 2237006 3 + 249 Mobile
element protein -none- D23_1c2406 Neut_1756
fig|6666666.60966.peg.2417 CDS 2240037 2237515 -3 - 2523 Aconitate
hydratase (EC TCA Cycle D23_1c2409 Neut_2457 4.2.1.3)
fig|6666666.60966.peg.2418 CDS 2240239 2240093 -1 - 147 Aconitate
hydratase (EC TCA Cycle D23_1c2410 NA 4.2.1.3)
fig|6666666.60966.peg.2419 CDS 2240661 2241623 3 + 963 Mobile
element protein -none- D23_1c2411 Neut_1278
fig|6666666.60966.peg.2421 CDS 2241835 2241987 1 + 153 Mobile
element protein -none- D23_1c2413 NA fig|6666666.60966.peg.2422 CDS
2242232 2242522 2 + 291 hypothetical protein -none- D23_1c2414 NA
fig|6666666.60966.peg.2423 CDS 2242506 2243450 3 + 945 Agmatinase
(EC Arginine and Ornithine D23_1c2415 Neut_2187 3.5.3.11)
Degradation; <br>Polyamine Metabolism
fig|6666666.60966.peg.2424 CDS 2243462 2245420 2 + 1959
Biosynthetic arginine Arginine and Ornithine D23_1c2416 Neut_2188
decarboxylase (EC Degradation; 4.1.1.19) <br>Polyamine
Metabolism fig|6666666.60966.peg.2425 CDS 2246086 2245436 -1 - 651
Mobile element protein -none- D23_1c2417 Neut_2189
fig|6666666.60966.peg.2426 CDS 2247251 2246148 -2 - 1104
hypothetical protein -none- D23_1c2418 Neut_2191
fig|6666666.60966.peg.2427 CDS 2247251 2247436 2 + 186 Mobile
element protein -none- D23_1c2419 Neut_2500
fig|6666666.60966.peg.2428 CDS 2247493 2248341 1 + 849 Mobile
element protein -none- D23_1c2420 Neut_1375
fig|6666666.60966.peg.2430 CDS 2249188 2249352 1 + 165 Mobile
element protein -none- D23_1c2422 Neut_2186
fig|6666666.60966.peg.2431 CDS 2249749 2251734 1 + 1986
Protein-L-isoaspartate Protein-L-isoaspartate O- D23_1c2423
Neut_2323 O-methyltransferase methyltransferase; (EC 2.1.1.77)
<br>Stationary phase repair cluster; <br>Ton and Tol
transport systems fig|6666666.60966.peg.2432 CDS 2252354 2253127 2
+ 774 hypothetical protein -none- D23_1c2424 Neut_2196
fig|6666666.60966.peg.2433 CDS 2253955 2253515 -1 - 441 tRNA
pseudouridine Colicin V and Bacteriocin D23_1c2425 Neut_2203
synthase A (EC 4.2.1.70) Production Cluster; <br>RNA
pseudouridine syntheses; <br>tRNA modification Bacteria;
<br>tRNA processing fig|6666666.60966.peg.2434 CDS 2254408
2254247 -1 - 162 hypothetical protein -none- D23_1c2426 NA
fig|6666666.60966.peg.2435 CDS 2256251 2254536 -2 - 1716
Selenoprotein O and Selenoprotein O D23_1c2427 Neut_2204
cysteine-containing homologs fig|6666666.60966.peg.2436 CDS 2256898
2257503 1 + 606 GCN5-related N- -none- D23_1c2429 Neut_2208
acetyltransferase fig|6666666.60966.peg.2437 CDS 2258004 2257552 -3
- 453 probable multiple -none- D23_1c2430 Neut_2211 antibiotic
resistance protein marC fig|6666666.60966.peg.2438 CDS 2258357
2258229 -2 - 129 hypothetical protein -none- D23_1c2431 Neut_2212
fig|6666666.60966.peg.2440 CDS 2259106 2259264 1 + 159 hypothetical
protein -none- D23_1c2432 NA fig|6666666.60966.peg.2441 CDS 2259280
2260221 1 + 942 Ornithine Arginine and Ornithine D23_1c2433
Neut_2213 cyclodeaminase (EC Degradation 4.3.1.12)
fig|6666666.60966.peg.2442 CDS 2260562 2261791 2 + 1230
hypothetical protein -none- D23_1c2434 Neut_2214
fig|6666666.60966.peg.2443 CDS 2262110 2262748 2 + 639 hypothetical
protein -none- D23_1c2435 Neut_2232 fig|6666666.60966.peg.2444 CDS
2262936 2263406 3 + 471 FIG00858867: -none- D23_1c2436 Neut_2233
hypothetical protein fig|6666666.60966.peg.2446 CDS 2264766 2263630
-3 - 1137 N-succinyl-L,L- Arginine Biosynthesis-- D23_1c2437
Neut_2234 diaminopimelate gjo; <br>Arginine desuccinylase (EC
Biosynthesis extended; 3.5.1.18) <br>Lysine Biosynthesis DAP
Pathway, GJO scratch fig|6666666.60966.peg.2447 CDS 2265597 2264815
-3 - 783 Methionine ABC Methionine D23_1c2438 Neut_2235 transporter
ATP-binding Biosynthesis; protein <br>Methionine Degradation
fig|6666666.60966.peg.2448 CDS 2266742 2265597 -2 - 1146 ABC-type
transport -none- D23_1c2439 Neut_2236 system involved in resistance
to organic solvents, permease component USSDB6A
fig|6666666.60966.peg.2449 CDS 2267603 2266767 -2 - 837
Prolipoprotein Lipoprotein Biosynthesis D23_1c2440 Neut_2237
diacylglyceryl transferase (EC 2.4.99.--)
fig|6666666.60966.peg.2450 CDS 2267740 2269413 1 + 1674
Dihydroxy-acid Branched-Chain Amino D23_1c2441 Neut_2238
dehydratase (EC Acid Biosynthesis 4.2.1.9)
fig|6666666.60966.peg.2451 CDS 2269430 2271499 2 + 2070 Thymidylate
kinase (EC pyrimidine conversions D23_1c2442 Neut_2241 2.7.4.9)
fig|6666666.60966.peg.2452 CDS 2271523 2271834 1 + 312 Cytochrome
c551/c552 Soluble cytochromes D23_1c2443 Neut_2242 and functionally
related electron carriers fig|6666666.60966.peg.2454 CDS 2272004
2272972 2 + 969 D-3-phosphoglycerate Glycine and Serine D23_1c2444
Neut_2243 dehydrogenase (EC Utilization; 1.1.1.95)
<br>Pyridoxin (Vitamin B6) Biosynthesis; <br>Serine
Biosynthesis fig|6666666.60966.peg.2455 CDS 2273050 2273595 1 + 546
dTDP-4- Rhamnose containing D23_1c2445 Neut_2244 dehydrorhamnose
3,5- glycans; <br>dTDP- epimerase (EC 5.1.3.13) rhamnose
synthesis fig|6666666.60966.peg.2456 CDS 2273700 2274983 3 + 1284
Permeases of the major -none- D23_1c2446 Neut_2245 facilitator
superfamily fig|6666666.60966.peg.2457 CDS 2275758 2274997 -3 - 762
hypothetical protein -none- D23_1c2447 NA
fig|6666666.60966.peg.2458 CDS 2275968 2276633 3 + 666 Chromosomal
Cell Division Subsystem D23_1c2449 Neut_2247 replication initiator
including YidCD; protein DnaA <br>DNA replication cluster 1
fig|6666666.60966.peg.2459 CDS 2276770 2277435 1 + 666
Phosphoserine Glycine and Serine D23_1c2450 Neut_2248 phosphatase
(EC Utilization; <br>Serine 3.1.3.3) Biosynthesis;
<br>Serine Biosynthesis fig|6666666.60966.peg.2460 CDS
2277481 2277846 1 + 366 FIG00859424: -none- D23_1c2451 Neut_2249
hypothetical protein fig|6666666.60966.peg.2461 CDS 2277800 2277958
2 + 159 hypothetical protein -none- D23_1c2452 NA
fig|6666666.60966.peg.2462 CDS 2277971 2279434 2 + 1464 Inosine-5'-
Purine conversions; D23_1c2453 Neut_2250 monophosphate
<br>Purine salvage dehydrogenase (EC cluster 1.1.1.205)
fig|6666666.60966.peg.2463 CDS 2279447 2281006 2 + 1560 GMP
synthase GMP synthase; <br>GMP D23_1c2454 Neut_2251
[glutamine- synthase; <br>Purine hydrolyzing], conversions;
<br>Purine amidotransferase conversions; <br>Purine
subunit (EC 6.3.5.2)/ salvage cluster; GMP synthase
<br>Purine salvage [glutamine- cluster hydrolyzing], ATP
pyrophosphatase subunit (EC 6.3.5.2) fig|6666666.60966.peg.2465 CDS
2282716 2281352 -1 - 1365 hypothetical protein -none- D23_1c2455 NA
fig|6666666.60966.peg.2466 CDS 2282899 2282762 -1 - 138 Mobile
element protein -none- D23_1c2456 Neut_2501
fig|6666666.60966.peg.2467 CDS 2283609 2282872 -3 - 738 Mobile
element protein -none- D23_1c2457 Neut_1888
fig|6666666.60966.peg.2468 CDS 2283851 2283666 -2 - 186 Mobile
element protein -none- D23_1c2458 Neut_2500
fig|6666666.60966.peg.2469 CDS 2285015 2284020 -2 - 996
hypothetical protein -none- D23_1c2459 NA
fig|6666666.60966.peg.2470 CDS 2285305 2285048 -1 - 258
hypothetical protein -none- D23_1c2460 NA
fig|6666666.60966.peg.2471 CDS 2285448 2285573 3 + 126 hypothetical
protein -none- D23_1c2461 NA fig|6666666.60966.peg.2472 CDS 2285631
2286293 3 + 663 Thiopurine S- -none- D23_1c2462 Neut_2272
methyltransferase (EC 2.1.1.67) fig|6666666.60966.peg.2473 CDS
2286615 2288795 3 + 2181 hypothetical protein -none- D23_1c2463
Neut_2273 fig|6666666.60966.peg.2474 CDS 2289016 2291046 1 + 2031
oligopeptide -none- D23_1c2464 Neut_2274 transporter
fig|6666666.60966.peg.2475 CDS 2291342 2291145 -2 - 198
FIG00859558: -none- D23_1c2465 Neut_2275 hypothetical protein
fig|6666666.60966.peg.2476 CDS 2291757 2291362 -3 - 396
FIG00859558: -none- D23_1c2466 Neut_2275 hypothetical protein
fig|6666666.60966.peg.2477 CDS 2292959 2291901 -2 - 1059 Putative
permease -none- D23_1c2467 Neut_2276 often clustered with de novo
purine synthesis fig|6666666.60966.peg.2478 CDS 2293039 2294097 1 +
1059 Phosphoribosylformylglycinamidine De Novo Purine D23_1c2468
Neut_2277 cyclo-ligase Biosynthesis (EC 6.3.3.1)
fig|6666666.60966.peg.2479 CDS 2294109 2294741 3 + 633
Phosphoribosylglycinamide 5-FCL-like protein; D23_1c2469 Neut_2278
formyltransferase <br>De Novo Purine (EC 2.1.2.2)
Biosynthesis fig|6666666.60966.peg.2480 CDS 2294738 2295460 2 + 723
FIG00859545: -none- D23_1c2470 Neut_2279 hypothetical protein
fig|6666666.60966.peg.2481 CDS 2295477 2296751 3 + 1275 Fmu
(Sun)/eukaryotic -none- D23_1c2471 Neut_2280
nucleolar NOL1/Nop2p; tRNAand rRNA cytosine-C5-methylases
fig|6666666.60966.peg.2482 CDS 2297068 2296832 -1 - 237
hypothetical protein -none- D23_1c2472 Neut_2281 PA0941
fig|6666666.60966.peg.2483 CDS 2297785 2297237 -1 - 549 InterPro
-none- D23_1c2473 Neut_2282 IPR000694:IPR001734
fig|6666666.60966.peg.2484 CDS 2297997 2297800 -3 - 198
hypothetical protein -none- D23_1c2474 Neut_2283
fig|6666666.60966.peg.2485 CDS 2298574 2299293 1 + 720 possible
-none- D23_1c2475 Neut_2284 transmembrane protein
fig|6666666.60966.peg.2486 CDS 2299389 2301113 3 + 1725 Diguanylate
-none- D23_1c2476 Neut_2285 cyclase/phosphodiesterase domain 2
(EAL) fig|6666666.60966.peg.2488 CDS 2301326 2301784 2 + 459
FKBP-type peptidyl- -none- D23_1c2477 Neut_2286 prolyl cis-trans
isomerase fig|6666666.60966.peg.2489 CDS 2302743 2301856 -3 - 888
Ribosome small Universal GTPases D23_1c2478 Neut_2287
subunit-stimulated GTPase EngC fig|6666666.60966.peg.2490 CDS
2303060 2302782 -2 - 279 Pterin-4-alpha- Pterin carbinolamine
D23_1c2479 Neut_2288 carbinolamine dehydratase dehydratase (EC
4.2.1.96) fig|6666666.60966.peg.2491 CDS 2304388 2303120 -1 - 1269
macromolecule -none- D23_1c2480 Neut_2289 metabolism; macromolecule
degradation; degradation of proteins, peptides, glycopeptides
fig|6666666.60966.peg.2492 CDS 2304540 2305085 3 + 546 3'-to-5' RNA
processing and D23_1c2481 Neut_2290 oligoribonuclease (orn)
degradation, bacterial fig|6666666.60966.peg.2493 CDS 2305123
2307678 1 + 2556 Glycogen Glycogen metabolism D23_1c2482 Neut_2291
phosphorylase (EC 2.4.1.1) fig|6666666.60966.peg.2494 CDS 2308460
2307702 -2 - 759 Pantoate--beta-alanine Coenzyme A D23_1c2483
Neut_2292 ligase (EC 6.3.2.1) Biosynthesis; <br>Coenzyme A
Biosynthesis cluster fig|6666666.60966.peg.2495 CDS 2309368 2308559
-1 - 810 3-methyl-2- Coenzyme A D23_1c2484 Neut_2293 oxobutanoate
Biosynthesis; hydroxymethyltransferase <br>Coenzyme A (EC
2.1.2.11) Biosynthesis cluster fig|6666666.60966.peg.2496 CDS
2310016 2309372 -1 - 645 Deoxyadenosine kinase Purine conversions;
D23_1c2485 Neut_2294 (EC 2.7.1.76)/ <br>Purine conversions
Deoxyguanosine kinase (EC 2.7.1.113) fig|6666666.60966.peg.2497 CDS
2310525 2310013 -3 - 513 2-amino-4-hydroxy-6- Folate Biosynthesis
D23_1c2486 Neut_2295 hydroxymethyldihydropteridine
pyrophosphokinase (EC 2.7.6.3) fig|6666666.60966.peg.2498 CDS
2311910 2310522 -2 - 1389 Poly(A) polymerase (EC Polyadenylation
D23_1c2487 Neut_2296 2.7.7.19) bacterial fig|6666666.60966.peg.2499
CDS 2313230 2312073 -2 - 1158 Cardiolipin synthetase Cardiolipin
synthesis; D23_1c2488 Neut_2297 (EC 2.7.8.--)
<br>Glycerolipid and Glycerophospholipid Metabolism in
Bacteria fig|6666666.60966.peg.2500 CDS 2314054 2313227 -1 - 828
Endonuclease/exonuclease/ -none- D23_1c2489 Neut_2298 phosphatase
family protein fig|6666666.60966.peg.2501 CDS 2315160 2314060 -3 -
1101 Quinolinate synthetase Mycobacterium D23_1c2490 Neut_2299 (EC
2.5.1.72) virulence operon possibly involved in quinolinate
biosynthesis; <br>NAD and NADP cofactor biosynthesis global
fig|6666666.60966.peg.2502 CDS 2315495 2316031 2 + 537 FIG00859627:
-none- D23_1c2491 Neut_2300 hypothetical protein
fig|6666666.60966.peg.2503 CDS 2316137 2316652 2 + 516 LptA,
protein essential Lipopolysaccharide D23_1c2492 Neut_2301 for LPS
transport across assembly the periplasm fig|6666666.60966.peg.2504
CDS 2316704 2317426 2 + 723 Lipopolysaccharide ABC
Lipopolysaccharide D23_1c2493 Neut_2302 transporter, ATP- assembly
binding protein LptB fig|6666666.60966.peg.2505 CDS 2317432 2318895
1 + 1464 RNA polymerase sigma- Flagellar motility; D23_1c2494
Neut_2303 54 factor RpoN <br>Flagellum;
<br>Transcription initiation, bacterial sigma factors
fig|6666666.60966.peg.2506 CDS 2319070 2319405 1 + 336 Ribosome
hibernation Ribosome activity D23_1c2495 Neut_2304 protein YhbH
modulation fig|6666666.60966.peg.2507 CDS 2319646 2320116 1 + 471
PTS system nitrogen- -none- D23_1c2496 Neut_2305 specific IIA
component, PtsN fig|6666666.60966.peg.2508 CDS 2320103 2321074 2 +
972 HPr HPr catabolite D23_1c2497 Neut_2306 kinase/phosphorylase
repression system (EC 2.7.1.--) (EC 2.7.4.--)
fig|6666666.60966.peg.2509 CDS 2321107 2321223 1 + 117 hypothetical
protein -none- D23_1c2498 NA fig|6666666.60966.peg.2510 CDS 2321260
2321874 1 + 615 3-polyprenyl-4- Ubiquinone D23_1c2499 Neut_2307
hydroxybenzoate Biosynthesis; carboxy-lyase UbiX (EC
<br>Ubiquinone 4.1.1.--) Biosynthesis-gjo
fig|6666666.60966.peg.2511 CDS 2322562 2321924 -1 - 639 5-
5-FCL-like protein; D23_1c2500 Neut_2308 formyltetrahydrofolate
<br>Folate Biosynthesis; cyclo-ligase (EC 6.3.3.2)
<br>One-carbon metabolism by tetrahydropterines
fig|6666666.60966.peg.2512 CDS 2323682 2322555 -2 - 1128
A/G-specific adenine DNA repair, bacterial D23_1c2501 Neut_2309
glycosylase (EC 3.2.2.--) fig|6666666.60966.peg.2513 CDS 2324249
2323704 -2 - 546 Intracellular septation CBSS-211586.9.peg.2729
D23_1c2503 Neut_2310 protein IspA fig|6666666.60966.peg.2514 CDS
2326043 2324346 -2 - 1698 Lipid A export ATP- KDO2-Lipid A
D23_1c2504 Neut_2311 binding/permease biosynthesis cluster 2
protein MsbA (EC 3.6.3.25) fig|6666666.60966.peg.2515 CDS 2327134
2326562 -1 - 573 hypothetical protein -none- D23_1c2505 Neut_2312
fig|6666666.60966.peg.2516 CDS 2329375 2327231 -1 - 2145 Copper
resistance Copper homeostasis D23_1c2506 Neut_2313 protein D
fig|6666666.60966.peg.2517 CDS 2329755 2329381 -3 - 375 Copper
resistance -none- D23_1c2507 Neut_2314 protein CopC precursor
fig|6666666.60966.peg.2518 CDS 2330496 2329909 -3 - 588
hypothetical protein -none- D23_1c2508 Neut_2074
fig|6666666.60966.peg.2519 CDS 2331308 2330568 -2 - 741 putative
(U92432) ORF4 -none- D23_1c2509 Neut_2316 (Nitrosospira sp. NpAV)
fig|6666666.60966.peg.2520 CDS 2332640 2331375 -2 - 1266
Particulate methane Particulate methane D23_1c2510 Neut_2317
monooxygenase B- monooxygenase subunit (EC 1.14.13.25) (pMMO)
fig|6666666.60966.peg.2521 CDS 2333470 2332640 -1 - 831 Particulate
methane Particulate methane D23_1c2511 Neut_2318 monooxygenase A-
monooxygenase subunit (EC 1.14.13.25) (pMMO)
fig|6666666.60966.peg.2522 CDS 2334459 2333644 -3 - 816 Particulate
methane Particulate methane D23_1c2512 Neut_2319 monooxygenase C-
monooxygenase subunit (EC 1.14.13.25) (pMMO)
fig|6666666.60966.peg.2523 CDS 2334883 2335908 1 + 1026 TsaC
protein (YrdC-Sua5 -none- D23_1c2513 Neut_2320 domains) required
for threonylcarbamoyladenosine t(6)A37 modification in tRNA
fig|6666666.60966.peg.2524 CDS 2335923 2336666 3 + 744 Hypothetical
protein -none- D23_1c2514 Neut_2321 CbbY fig|6666666.60966.peg.2525
CDS 2337688 2336702 -1 - 987 Lipoprotein NlpD Stationary phase
repair D23_1c2515 Neut_2322 cluster fig|6666666.60966.peg.2526 CDS
2338471 2337803 -1 - 669 Protein-L-isoaspartate
Protein-L-isoaspartate O- D23_1c2516 Neut_2323 O-methyltransferase
methyltransferase; (EC 2.1.1.77) <br>Stationary phase repair
cluster; <br>Ton and Tol transport systems
fig|6666666.60966.peg.2528 CDS 2339405 2338662 -2 - 744
5-nucleotidase SurE (EC Housecleaning D23_1c2517 Neut_2324 3.1.3.5)
@ nucleoside triphosphate Exopolyphosphatase pyrophosphatases; (EC
3.6.1.11) <br>Phosphate metabolism; <br>Polyphosphate;
<br>Stationary phase repair cluster
fig|6666666.60966.peg.2529 CDS 2340272 2339964 -2 - 309 Integration
host factor DNA structural proteins, D23_1c2519 Neut_2325 alpha
subunit bacterial fig|6666666.60966.peg.2530 CDS 2342785 2340485 -1
- 2301 Phenylalanyl-tRNA tRNA aminoacylation, D23_1c2520 Neut_2326
synthetase beta chain Phe (EC 6.1.1.20) fig|6666666.60966.peg.2531
CDS 2343901 2342882 -1 - 1020 Phenylalanyl-tRNA tRNA
aminoacylation, D23_1c2521 Neut_2327 synthetase alpha chain Phe (EC
6.1.1.20) fig|6666666.60966.peg.2532 CDS 2344231 2343989 -1 - 243
LSU ribosomal protein -none- D23_1c2522 Neut_2328 L20p
fig|6666666.60966.peg.2533 CDS 2345202 2344723 -3 - 480 Translation
initiation Translation initiation D23_1c2524 Neut_2330 factor 3
factors bacterial fig|6666666.60966.peg.2534 CDS 2347209 2345302 -3
- 1908 Threonyl-tRNA tRNA aminoacylation, D23_1c2525 Neut_2331
synthetase (EC 6.1.1.3) Thr fig|6666666.60966.peg.2535 CDS 2348256
2347537 -3 - 720 Cytochrome c-type -none- D23_1c2526 Neut_1790
protein TorY fig|6666666.60966.peg.2536 CDS 2348966 2348259 -2 -
708 Cytochrome c family -none- D23_1c2527 Neut_2333 protein
fig|6666666.60966.peg.2537 CDS 2350169 2349048 -2 - 1122
FIG00859557: -none- D23_1c2528 Neut_1792 hypothetical protein
fig|6666666.60966.peg.2538 CDS 2351878 2350166 -1 - 1713
Hydroxylamine -none- D23_1c2529 Neut_2335 oxidoreductase precursor
(EC 1.7.3.4) fig|6666666.60966.peg.2539 CDS 2352170 2353255 2 +
1086 tRNA-specific 2- RNA methylation D23_1c2530 Neut_2336
thiouridylase MnmA fig|6666666.60966.peg.2540 CDS 2354395 2353256
-1 - 1140 Twitching motility -none- D23_1c2531 Neut_2337 protein
PilT fig|6666666.60966.peg.2541 CDS 2355448 2354405 -1 - 1044
Twitching motility -none- D23_1c2532 Neut_2338 protein PilT
fig|6666666.60966.peg.2543 CDS 2355643 2356359 1 + 717 Hypothetical
protein A Hypothetical Protein D23_1c2533 Neut_2339 YggS, proline
synthase Related to Proline co-transcribed bacterial Metabolism;
<br>CBSS- homolog PROSC 630.2.peg.3360
fig|6666666.60966.peg.2544 CDS 2356597 2356328 -1 - 270 4Fe--4S
ferredoxin, iron- Inorganic Sulfur D23_1c2534 Neut_2340 sulfur
binding Assimilation fig|6666666.60966.peg.2545 CDS 2357097 2356603
-3 - 495 Phosphopantetheine CBSS- D23_1c2535 Neut_2341
adenylyltransferase (EC 266117.6.peg.1260; 2.7.7.3)
<br>CBSS-269801.1.peg.1715; <br>Coenzyme A Biosynthesis
fig|6666666.60966.peg.2546 CDS 2357644 2357090 -1 - 555 16S rRNA
CBSS- D23_1c2536 Neut_2342 (guanine(966)-N(2))- 266117.6.peg.1260;
methyltransferase (EC <br>CBSS- 2.1.1.171) ## SSU rRNA
269801.1.peg.1715;
m(2)G966 <br>Heat shock Cell division Proteases and a
Methyltransferase; <br>RNA methylation
fig|6666666.60966.peg.2547 CDS 2358960 2357659 -3 - 1302 FIG015287:
Zinc Heat shock Cell division D23_1c2537 Neut_2343 protease
Proteases and a Methyltransferase fig|6666666.60966.peg.2548 CDS
2359437 2359126 -3 - 312 Transposase -none- D23_1c2538 Neut_2344
fig|6666666.60966.peg.2549 CDS 2360187 2359819 -3 - 369 Mobile
element protein -none- D23_1c2539 Neut_1814
fig|6666666.60966.peg.2550 CDS 2360570 2360247 -2 - 324 Putative
periplasmic -none- D23_1c2540 Neut_2357 protein
fig|6666666.60966.peg.2551 CDS 2361073 2360771 -1 - 303
hypothetical protein -none- D23_1c2541 Neut_2349
fig|6666666.60966.peg.2552 CDS 2361307 2361110 -1 - 198 CsbD family
protein -none- D23_1c2542 Neut_2359 fig|6666666.60966.peg.2553 CDS
2361551 2361384 -2 - 168 protein of unknown -none- D23_1c2543 NA
function DUF1328 fig|6666666.60966.peg.2554 CDS 2361863 2362066 2 +
204 Mobile element protein -none- D23_1c2544 Neut_2365
fig|6666666.60966.peg.2555 CDS 2362071 2362247 3 + 177 hypothetical
protein -none- D23_1c2545 NA fig|6666666.60966.peg.2556 CDS 2362394
2362957 2 + 564 Alkyl hydroperoxide Thioredoxin-disulfide
D23_1c2546 Neut_2366 reductase protein C (EC reductase 1.6.4.--)
fig|6666666.60966.peg.2557 CDS 2363052 2363633 3 + 582 putative
lipoprotein -none- D23_1c2547 Neut_2367 fig|6666666.60966.peg.2558
CDS 2364440 2363661 -2 - 780 Putative -none- D23_1c2548 Neut_2368
stomatin/prohibitin- family membrane protease subunit aq_911
fig|6666666.60966.peg.2559 CDS 2365869 2364442 -3 - 1428 Putative
membrane- -none- D23_1c2549 Neut_2369 bound ClpP-class protease
associated with aq_911 fig|6666666.60966.peg.2560 CDS 2366482
2365880 -1 - 603 ADP-ribose CBSS-216591.1.peg.168; D23_1c2550
Neut_2370 pyrophosphatase (EC <br>NADand NADP 3.6.1.13)
cofactor biosynthesis global; <br>Nudix proteins (nucleoside
triphosphate hydrolases) fig|6666666.60966.peg.2561 CDS 2367579
2366665 -3 - 915 putative membrane -none- D23_1c2551 Neut_2371
protein fig|6666666.60966.peg.2562 CDS 2367673 2368539 1 + 867
Protein YicC CBSS-323097.3.peg.2594 D23_1c2552 Neut_2372
fig|6666666.60966.peg.2563 CDS 2369652 2368633 -3 - 1020
C4-dicarboxylate -none- D23_1c2553 Neut_2373 transporter/malic acid
transport protein fig|6666666.60966.peg.2564 CDS 2371015 2370053 -1
- 963 Mobile element protein -none- D23_1c2554 Neut_1746
fig|6666666.60966.peg.2565 CDS 2371724 2371065 -2 - 660
Glucose-1-phosphate Rhamnose containing D23_1c2555 Neut_2374
thymidylyltransferase glycans; <br>dTDP- (EC 2.7.7.24)
rhamnose synthesis fig|6666666.60966.peg.2566 CDS 2372737 2371739
-1 - 999 COG3178: Predicted -none- D23_1c2556 Neut_2375
phosphotransferase related to Ser/Thr protein kinases
fig|6666666.60966.peg.2567 CDS 2372902 2373210 1 + 309 Putative
cytoplasmic -none- D23_1c2557 Neut_2376 protein
fig|6666666.60966.peg.2568 CDS 2373276 2374775 3 + 1500 MG(2+)
CHELATASE -none- D23_1c2559 Neut_2377 FAMILY PROTEIN/ ComM-related
protein fig|6666666.60966.peg.2569 CDS 2376191 2374794 -2 - 1398
Replicative DNA -none- D23_1c2560 Neut_2378 helicase (EC 3.6.1.--)
fig|6666666.60966.peg.2571 CDS 2376752 2376297 -2 - 456 LSU
ribosomal protein Primosomal replication D23_1c2561 Neut_2379 L9p
protein N clusters with ribosomal proteins
fig|6666666.60966.peg.2572 CDS 2377049 2376771 -2 - 279 SSU
ribosomal protein Primosomal replication D23_1c2562 Neut_2380 S18p
@ SSU ribosomal protein N clusters with protein S18p, zinc-
ribosomal proteins independent fig|6666666.60966.peg.2573 CDS
2377399 2377091 -1 - 309 Primosomal replication Primosomal
replication D23_1c2563 Neut_2381 protein N protein N clusters with
ribosomal proteins fig|6666666.60966.peg.2574 CDS 2377721 2377401
-2 - 321 SSU ribosomal protein Primosomal replication D23_1c2564
Neut_2382 S6p protein N clusters with ribosomal proteins
fig|6666666.60966.peg.2576 CDS 2378765 2378340 -2 - 426
hypothetical protein -none- D23_1c2565 NA
fig|6666666.60966.peg.2578 CDS 2379069 2380031 3 + 963 Mobile
element protein -none- D23_1c2566 Neut_1746
fig|6666666.60966.peg.2580 CDS 2380409 2380864 2 + 456 Mobile
element protein -none- D23_1c2567 Neut_0883
fig|6666666.60966.peg.2581 CDS 2381862 2380975 -3 - 888
Acetylglutamate kinase Arginine Biosynthesis-- D23_1c2568 Neut_2384
(EC 2.7.2.8) gjo; <br>Arginine Biosynthesis extended
fig|6666666.60966.peg.2582 CDS 2382398 2381919 -2 - 480 type IV
pili signal -none- D23_1c2569 Neut_2385 transduction protein Pill
fig|6666666.60966.peg.2583 CDS 2382774 2382427 -3 - 348 twitching
motility -none- D23_1c2570 Neut_2386 protein PilH
fig|6666666.60966.peg.2584 CDS 2383169 2383639 2 + 471 21 kDa
hemolysin CBSS-160492.1.peg.550 D23_1c2571 Neut_2387 precursor
fig|6666666.60966.peg.2585 CDS 2383676 2385043 2 + 1368 Fe--S
protein, homolog -none- D23_1c2572 Neut_2388 of lactate
dehydrogenase SO1521 fig|6666666.60966.peg.2586 CDS 2386032 2385136
-3 - 897 Heme O synthase, Biogenesis of D23_1c2573 Neut_2389
protoheme IX cytochrome c oxidases; farnesyltransferase (EC
<br>CBSS- 2.5.1.--) COX10-CtaB 196164.1.peg.1690;
<br>CBSS- 316057.3.peg.563 fig|6666666.60966.peg.2587 CDS
2386422 2386123 -3 - 300 Probable -none- D23_1c2574 Neut_2390
transmembrane protein fig|6666666.60966.peg.2588 CDS 2387398
2386679 -1 - 720 Cytochrome oxidase Biogenesis of D23_1c2575
Neut_2391 biogenesis protein cytochrome c oxidases; Surf1,
facilitates heme <br>CBSS- A insertion 316057.3.peg.563
fig|6666666.60966.peg.2589 CDS 2388336 2387491 -3 - 846 Cytochrome
c oxidase CBSS-316057.3.peg.563; D23_1c2576 Neut_2392 polypeptide
III (EC <br>Terminal 1.9.3.1) cytochrome C oxidases
fig|6666666.60966.peg.2590 CDS 2389047 2388529 -3 - 519 Cytochrome
oxidase Biogenesis of cytochrome c oxidases; D23_1c2577 Neut_2393
biogenesis protein <br>CBSS- Cox11-CtaG, copper
316057.3.peg.563 delivery to Cox1 fig|6666666.60966.peg.2591 CDS
2390759 2389182 -2 - 1578 Cytochrome c oxidase Terminal cytochrome
C D23_1c2578 Neut_2394 polypeptide I (EC oxidases 1.9.3.1)
fig|6666666.60966.peg.2592 CDS 2391643 2390819 -1 - 825 Cytochrome
c oxidase CBSS-316057.3.peg.563; D23_1c2579 Neut_2395 polypeptide
II (EC <br>Terminal 1.9.3.1) cytochrome C oxidases
fig|6666666.60966.peg.2594 CDS 2392145 2392567 2 + 423 Putative
TEGT family CBSS-326442.4.peg.1852 D23_1c2580 NA carrier/transport
protein fig|6666666.60966.peg.2595 CDS 2392600 2392884 1 + 285
Putative TEGT family CBSS-326442.4.peg.1852 D23_1c2581 Neut_1715
carrier/transport protein fig|6666666.60966.peg.2596 CDS 2393084
2393302 2 + 219 Copper chaperone Copper homeostasis D23_1c2582
Neut_2397 fig|6666666.60966.peg.2597 CDS 2393426 2394394 2 + 969
Acetyl-coenzyme A Fatty Acid Biosynthesis D23_1c2583 Neut_2398
carboxyl transferase FASII alpha chain (EC 6.4.1.2)
fig|6666666.60966.peg.2598 CDS 2394357 2395742 3 + 1386
tRNA(Ile)-lysidine -none- D23_1c2584 Neut_2399 synthetase
fig|6666666.60966.peg.2599 CDS 2395746 2396807 3 + 1062
dTDP-glucose 4,6- CBSS- D23_1c2585 Neut_2400 dehydratase (EC
296591.1.peg.2330; 4.2.1.46) <br>Rhamnose containing glycans;
<br>dTDP-rhamnose synthesis fig|6666666.60966.peg.2600 CDS
2396804 2397700 2 + 897 dTDP-4- Rhamnose containing D23_1c2586
Neut_2401 dehydrorhamnose glycans; <br>dTDP- reductase (EC
rhamnose synthesis 1.1.1.133) fig|6666666.60966.peg.2601 CDS
2398663 2397710 -1 - 954 InterPro IPR002142 -none- D23_1c2587
Neut_2402 COGs COG0616 fig|6666666.60966.peg.2602 CDS 2399353
2398691 -1 - 663 Outer membrane Ton and Tol transport D23_1c2588
Neut_2403 lipoprotein omp16 systems precursor
fig|6666666.60966.peg.2603 CDS 2400398 2399562 -2 - 837 SH3, type 3
domain -none- D23_1c2590 Neut_2404 protein
fig|6666666.60966.peg.2604 CDS 2400602 2401477 2 + 876
esterase/lipase/thioesterase -none- D23_1c2591 Neut_2408 family
active site fig|6666666.60966.peg.2605 CDS 2402010 2401492 -3 - 519
Mobile element protein -none- D23_1c2592 Neut_2502
fig|6666666.60966.peg.2606 CDS 2402097 2403560 3 + 1464
hypothetical protein -none- D23_1c2593 Neut_2493
fig|6666666.60966.peg.2607 CDS 2403699 2404946 3 + 1248 Lipoprotein
releasing Lipopolysaccharide D23_1c2594 Neut_2492 system
transmembrane assembly; protein LolE <br>Lipoprotein sorting
system fig|6666666.60966.peg.2608 CDS 2404939 2405613 1 + 675
Lipoprotein releasing Lipopolysaccharide D23_1c2595 Neut_2491
system ATP-binding assembly; protein LolD <br>Lipoprotein
sorting system fig|6666666.60966.peg.2609 CDS 2406957 2405641 -3 -
1317 FIG065221: Holliday CBSS-83333.1.peg.876 D23_1c2596 Neut_2490
junction DNA helicase fig|6666666.60966.peg.2610 CDS 2407570
2406950 -1 - 621 Outer membrane CBSS-83333.1.peg.876; D23_1c2597
Neut_2489 lipoprotein carrier <br>Lipopolysaccharide protein
LolA assembly; <br>Lipoprotein sorting system
fig|6666666.60966.peg.2611 CDS 2409936 2407630 -3 - 2307 Cell
division protein Bacterial cell Division; D23_1c2598 Neut_2488 FtsK
<br>Bacterial cytoskeleton; <br>Bacterial RNA-
metabolizing Zn- dependent hydrolases; <br>CBSS-
83333.1.peg.876 fig|6666666.60966.peg.2612 CDS 2411206 2410151 -1 -
1056 InterPro IPR002110 -none- D23_1c2600 Neut_2487 COGs COG0666
fig|6666666.60966.peg.2613 CDS 2412939 2411203 -3 - 1737 Succinate
Succinate D23_1c2601 Neut_2486 dehydrogenase dehydrogenase;
flavoprotein subunit (EC <br>TCA Cycle 1.3.99.1)
fig|6666666.60966.peg.2614 CDS 2413237 2412968 -1 - 270 Succinate
Succinate D23_1c2602 Neut_2485 dehydrogenase dehydrogenase
hydrophobic membrane anchor protein fig|6666666.60966.peg.2615 CDS
2413803 2413315 -3 - 489 Succinate Succinate D23_1c2603 Neut_2484
dehydrogenase dehydrogenase cytochrome b-556 subunit
fig|6666666.60966.peg.2616 CDS 2413889 2415583 2 + 1695 CTP
synthase (EC CTP synthase (EC D23_1c2604 Neut_2483 6.3.4.2)
6.3.4.2) cluster; <br>pyrimidine conversions
fig|6666666.60966.peg.2617 CDS 2415872 2417158 2 + 1287 Enolase (EC
4.2.1.11) Glycolysis and D23_1c2605 Neut_2482
Gluconeogenesis fig|6666666.60966.peg.2618 CDS 2417185 2417436 1 +
252 Cell division protein Bacterial cell Division; D23_1c2606
Neut_2481 DivIC (FtsB), stabilizes <br>Bacterial FtsL against
RasP cytoskeleton; cleavage <br>Stationary phase repair
cluster fig|6666666.60966.peg.2619 CDS 2417726 2417860 2 + 135
hypothetical protein -none- D23_1c2607 NA
fig|6666666.60966.peg.2621 CDS 2419576 2418317 -1 - 1260
Transcription Transcription factors D23_1c2609 Neut_2479
termination factor Rho bacterial fig|6666666.60966.peg.2622 CDS
2420006 2419791 -2 - 216 Thioredoxin -none- D23_1c2610 Neut_2478
fig|6666666.60966.peg.2624 CDS 2420605 2421762 1 + 1158
Membrane-bound lytic Murein Hydrolases; D23_1c2611 Neut_2477 murein
transglycosylase <br>Peptidoglycan B precursor (EC 3.2.1.--)
Biosynthesis fig|6666666.60966.peg.2625 CDS 2422278 2421835 -3 -
444 Universal stress protein -none- D23_1c2612 Neut_2476 family
COG0589 fig|6666666.60966.peg.2626 CDS 2424743 2422389 -2 - 2355
Partial urea carboxylase Urea carboxylase and D23_1c2613 Neut_2475
2 (EC 6.3.4.6) Allophanate hydrolase cluster; <br>Urea
decomposition fig|6666666.60966.peg.2627 CDS 2425462 2424797 -1 -
666 Urea carboxylase- Urea decomposition D23_1c2614 Neut_2474
related aminomethyltransferase (EC 2.1.2.10)
fig|6666666.60966.peg.2628 CDS 2426187 2425459 -3 - 729 Urea
carboxylase- Urea decomposition D23_1c2615 Neut_2473 related
aminomethyltransferase (EC 2.1.2.10) fig|6666666.60966.peg.2629 CDS
2427740 2426202 -2 - 1539 Urea carboxylase- Urea decomposition
D23_1c2616 Neut_2472 related amino acid permease
fig|6666666.60966.peg.2630 CDS 2427773 2427892 2 + 120 hypothetical
protein -none- D23_1c2617 NA fig|6666666.60966.peg.2631 CDS 2428128
2428319 3 + 192 hypothetical protein -none- D23_1c2618 NA
fig|6666666.60966.peg.2632 CDS 2428646 2428518 -2 - 129
hypothetical protein -none- D23_1c2620 NA
fig|6666666.60966.peg.2633 CDS 2428671 2432291 3 + 3621 Urea
carboxylase (EC Urea carboxylase and D23_1c2621 Neut_2470 6.3.4.6)
Allophanate hydrolase cluster; <br>Urea decomposition
fig|6666666.60966.peg.2634 CDS 2433643 2432279 -1 - 1365
Membrane-bound lytic CBSS-228410.1.peg.134; D23_1c2622 Neut_2469
murein transglycosylase <br>CBSS- D precursor (EC 3.2.1.--)
342610.3.peg.1536; <br>Murein Hydrolases
fig|6666666.60966.peg.2635 CDS 2434924 2433791 -1 - 1134
Ribonucleotide Ribonucleotide D23_1c2623 Neut_2468 reductase of
class Ia reduction (aerobic), beta subunit (EC 1.17.4.1)
fig|6666666.60966.peg.2636 CDS 2437918 2434976 -1 - 2943
Ribonucleotide Ribonucleotide D23_1c2624 Neut_2467 reductase of
class Ia reduction (aerobic), alpha subunit (EC 1.17.4.1)
fig|6666666.60966.peg.2637 CDS 2438096 2441536 2 + 3441
Long-chain-fatty-acid-- Biotin biosynthesis; D23_1c2625 Neut_2466
CoA ligase (EC 6.2.1.3) <br>Biotin synthesis cluster;
<br>Fatty acid metabolism cluster fig|6666666.60966.peg.2638
CDS 2441648 2441788 2 + 141 hypothetical protein -none- D23_1c2626
NA fig|6666666.60966.peg.2639 CDS 2441958 2441845 -3 - 114
hypothetical protein -none- D23_1c2627 NA
fig|6666666.60966.peg.2640 CDS 2441984 2442337 2 + 354
S-adenosylmethionine Polyamine Metabolism D23_1c2628 Neut_2465
decarboxylase proenzyme (EC 4.1.1.50), prokaryotic class 1B
fig|6666666.60966.peg.2641 CDS 2442337 2443296 1 + 960 Spermidine
synthase Polyamine Metabolism D23_1c2629 Neut_2464 (EC 2.5.1.16)
fig|6666666.60966.peg.2642 CDS 2444178 2443342 -3 - 837 Cytochrome
c family -none- D23_1c2630 Neut_2463 protein
fig|6666666.60966.peg.2643 CDS 2446065 2444275 -3 - 1791 ABC
transporter, fused -none- D23_1c2631 Neut_2462 permease and ATPase
domains fig|6666666.60966.peg.2644 CDS 2446735 2446268 -1 - 468
Single-stranded DNA- DNA repair, bacterial D23_1c2632 Neut_2461
binding protein fig|6666666.60966.peg.2645 CDS 2448142 2446736 -1 -
1407 Putative transport -none- D23_1c2633 Neut_2460 protein
fig|6666666.60966.peg.2646 CDS 2448217 2451054 1 + 2838
Excinuclease ABC DNA repair, UvrABC D23_1c2634 Neut_2459 subunit A
system fig|6666666.60966.peg.2647 CDS 2451051 2452322 3 + 1272
D-glycerate 2-kinase (EC Glycerate metabolism D23_1c2635 Neut_2458
2.7.1.--) fig|6666666.60966.peg.2648 CDS 2455286 2452443 -2 - 2844
Aconitate hydratase (EC TCA Cycle D23_1c2637 Neut_2457 4.2.1.3)
fig|6666666.60966.peg.2649 CDS 2455429 2456334 1 + 906 Aldose
1-epimerase -none- D23_1c2638 Neut_2456 fig|6666666.60966.peg.2650
CDS 2456378 2456941 2 + 564 NADPH-dependent -none- D23_1c2639
Neut_2455 FMN reductase fig|6666666.60966.peg.2651 CDS 2457281
2457051 -2 - 231 HrgA protein -none- D23_1c2640 Neut_2454
fig|6666666.60966.peg.2652 CDS 2457998 2457480 -2 - 519 HrgA
protein -none- D23_1c2641 NA fig|6666666.60966.peg.2653 CDS 2459350
2458013 -1 - 1338 hypothetical protein -none- D23_1c2642 NA
fig|6666666.60966.peg.2654 CDS 2460249 2459347 -3 - 903
hypothetical protein -none- D23_1c2643 NA
fig|6666666.60966.peg.2655 CDS 2463305 2460264 -2 - 3042 Type I
restriction- Restriction-Modification D23_1c2644 NA modification
system, System; <br>Type I restriction subunit R (EC
Restriction-Modification 3.1.21.3) fig|6666666.60966.peg.2656 CDS
2463943 2463341 -1 - 603 hypothetical protein -none- D23_1c2645 NA
fig|6666666.60966.peg.2657 CDS 2465348 2463960 -2 - 1389 Type I
restriction- Restriction-Modification D23_1c2646 NA modification
system, System; <br>Type I specificity subunit S (EC
Restriction-Modification 3.1.21.3) fig|6666666.60966.peg.2658 CDS
2467567 2465348 -1 - 2220 Type I restriction-
Restriction-Modification D23_1c2647 Neut_0541 modification system,
System; <br>Type I DNA-methyltransferase
Restriction-Modification subunit M (EC 2.1.1.72)
fig|6666666.60966.peg.2659 CDS 2468029 2467751 -1 - 279 Type I
restriction- Restriction-Modification D23_1c2648 Neut_2448
modification system, System; <br>Type I DNA-methyltransferase
Restriction-Modification subunit M (EC 2.1.1.72)
fig|6666666.60966.peg.2660 CDS 2468945 2468235 -2 - 711 RNA
polymerase sigma Flagellar motility; D23_1c2650 Neut_2447 factor
for flagellar <br>Flagellum; operon <br>Transcription
initiation, bacterial sigma factors fig|6666666.60966.peg.2661 CDS
2469847 2468954 -1 - 894 Flagellar synthesis Flagellar motility;
D23_1c2651 Neut_2446 regulator FleN <br>Flagellum
fig|6666666.60966.peg.2662 CDS 2471090 2469840 -2 - 1251 Flagellar
biosynthesis Flagellar motility; D23_1c2652 Neut_2445 protein FlhF
<br>Flagellum fig|6666666.60966.peg.2663 CDS 2473171 2471087
-1 - 2085 Flagellar biosynthesis Flagellar motility; D23_1c2653
Neut_2444 protein FlhA <br>Flagellum
fig|6666666.60966.peg.2664 CDS 2474349 2473219 -3 - 1131 Flagellar
biosynthesis Flagellar motility; D23_1c2654 Neut_2443 protein FlhB
<br>Flagellum fig|6666666.60966.peg.2665 CDS 2476208 2474601
-2 - 1608 Peptide chain release Translation termination D23_1c2655
Neut_2442 factor 3 factors bacterial fig|6666666.60966.peg.2666 CDS
2478262 2476208 -1 - 2055 Dipeptide transport ABC transporter
D23_1c2656 Neut_2441 ATP-binding protein dipeptide (TC 3.A.1.5.2)
DppF (TC 3.A.1.5.2) fig|6666666.60966.peg.2667 CDS 2479752 2478259
-3 - 1494 Oligopeptide transport -none- D23_1c2657 Neut_2440 system
permease protein fig|6666666.60966.peg.2669 CDS 2480032 2480334 1 +
303 Negative regulator of Flagellum D23_1c2658 Neut_2439 flagellin
synthesis fig|6666666.60966.peg.2670 CDS 2480417 2480800 2 + 384
Flagellar biosynthesis Flagellum D23_1c2659 Neut_2438 protein FlgN
fig|6666666.60966.peg.2671 CDS 2481184 2483109 1 + 1926 tRNA
uridine 5- Cell Division Subsystem D23_1c2660 Neut_2437
carboxymethylaminomethyl including YidCD; modification
<br>RNA modification enzyme GidA and chromosome partitioning
cluster; <br>mnm5U34 biosynthesis bacteria; <br>tRNA
modification Bacteria fig|6666666.60966.peg.2672 CDS 2483084
2483728 2 + 645 rRNA small subunit 7- Cell Division Subsystem
D23_1c2661 Neut_2436 methylguanosine (m7G) including YidCD;
methyltransferase GidB <br>RNA methylation; <br>RNA
modification and chromosome partitioning cluster
fig|6666666.60966.peg.2673 CDS 2483792 2484556 2 + 765 Chromosome
(plasmid) Bacterial Cell Division; D23_1c2662 Neut_2435
partitioning protein <br>Bacterial ParA/Sporulation
Cytoskeleton; initiation inhibitor <br>Bacterial protein Soj
Cytoskeleton; <br>Cell Division Subsystem including YidCD;
<br>RNA modification and chromosome partitioning cluster
fig|6666666.60966.peg.2674 CDS 2484637 2485440 1 + 804 Chromosome
(plasmid) Bacterial Cytoskeleton; D23_1c2663 Neut_2434 partitioning
protein <br>Bacterial ParB/Stage 0 Cytoskeleton;
<br>Cell sporulation protein J Division Subsystem including
YidCD; <br>RNA modification and chromosome partitioning
cluster fig|6666666.60966.peg.2675 CDS 2485777 2488083 1 + 2307
Glucose-6-phosphate Glycolysis and D23_1c2664 Neut_2433 isomerase
(EC 5.3.1.9) Gluconeogenesis fig|6666666.60966.peg.2676 CDS 2488076
2489131 2 + 1056 6-phosphogluconate D-gluconate and D23_1c2665
Neut_2432 dehydrogenase, ketogluconates decarboxylating (EC
metabolism; 1.1.1.44) <br>Pentose phosphate pathway
fig|6666666.60966.peg.2677 CDS 2489149 2490591 1 + 1443
Glucose-6-phosphate 1- Pentose phosphate D23_1c2666 Neut_2431
dehydrogenase (EC pathway 1.1.1.49) fig|6666666.60966.peg.2678 CDS
2490598 2490741 1 + 144 hypothetical protein -none- D23_1c2667 NA
fig|6666666.60966.peg.2679 CDS 2491345 2490770 -1 - 576 putative
membrane -none- D23_1c2668 Neut_2430 protein
fig|6666666.60966.peg.2680 CDS 2491701 2492270 3 + 570 DedA family
inner DedA family of inner D23_1c2669 Neut_2429 membrane protein
membrane proteins YohD fig|6666666.60966.peg.2681 CDS 2492664
2492897 3 + 234 Mobile element protein -none- D23_1c2671 Neut_2428
fig|6666666.60966.peg.2682 CDS 2493050 2494789 2 + 1740 ABC-type
anion -none- D23_1c2672 Neut_2427 transport system, duplicated
permease component fig|6666666.60966.peg.2683 CDS 2494811 2496100 2
+ 1290 ABC-type Alkanesulfonate D23_1c2673 Neut_2426
nitrate/sulfonate/bicarbonate assimilation transport system, ATPase
component fig|6666666.60966.peg.2684 CDS 2499268 2496263 -1 - 3006
Exonuclease SbcC DNA repair, bacterial; D23_1c2676 Neut_2425
<br>Rad50-Mre11 DNA repair cluster
fig|6666666.60966.peg.2685 CDS 2499230 2499520 2 + 291 hypothetical
protein -none- D23_1c2677 NA fig|6666666.60966.peg.2686 CDS 2500770
2499526 -3 - 1245 Exonuclease SbcD DNA repair, bacterial;
D23_1c2678 Neut_2424 <br>Rad50-Mre11 DNA repair cluster
fig|6666666.60966.peg.2687 CDS 2501402 2500767 -2 - 636
FIG01057587: -none- D23_1c2679 NA hypothetical protein
fig|6666666.60966.peg.2688 CDS 2501615 2502037 2 + 423 Mobile
element protein -none- D23_1c2680 Neut_2450
fig|6666666.60966.peg.2689 CDS 2502217 2502050 -1 - 168
hypothetical protein -none- D23_1c2681 NA
fig|6666666.60966.peg.2691 CDS 2503677 2502628 -3 - 1050
hypothetical protein -none- D23_1c2682 Neut_2415
fig|6666666.60966.peg.2692 CDS 2503893 2504105 3 + 213 hypothetical
protein -none- D23_1c2683 NA fig|6666666.60966.peg.2693 CDS 2505239
2504595 -2 - 645 hypothetical protein -none- D23_1c2685 NA
fig|6666666.60966.peg.2694 CDS 2506092 2505229 -3 - 864 Mobile
element protein -none- D23_1c2686 Neut_2192
fig|6666666.60966.peg.2695 CDS 2506385 2506089 -2 - 297 Mobile
element protein -none- D23_1c2687 Neut_2193
fig|6666666.60966.peg.2696 CDS 2506924 2506445 -1 - 480 DNA
primase/helicase, Phage replication D23_1c2688 NA phage-associated
fig|6666666.60966.peg.2697 CDS 2507166 2506921 -3 - 246
hypothetical protein -none- D23_1c2689 NA
fig|6666666.60966.peg.2698 CDS 2507393 2507166 -2 - 228
hypothetical protein -none- D23_1c2690 NA
fig|6666666.60966.peg.2699 CDS 2507735 2508577 2 + 843 hypothetical
protein -none- D23_1c2691 NA fig|6666666.60966.peg.2700 CDS 2508650
2509111 2 + 462 Putative bacteriophage- -none- D23_1c2692 NA
related protein fig|6666666.60966.peg.2701 CDS 2509108 2510448 1 +
1341 probable DNA invertase -none- D23_1c2693 Neut_2563
fig|6666666.60966.peg.2702 CDS 2510478 2510897 3 + 420 elements of
external -none- D23_1c2694 NA origin; phage-related functions and
prophages fig|6666666.60966.peg.2703 CDS 2512240 2511590 -1 - 651
Similar to 2-phosphoglycolate D23_1c2696 Neut_2506 phosphoglycolate
salvage phosphatase, clustered with ubiquinone biosynthesis SAM-
dependent O- methyltransferase fig|6666666.60966.peg.2704 CDS
2512973 2512269 -2 - 705 3-demethylubiquinol 3- Ubiquinone
D23_1c2697 Neut_2507 O-methyltransferase Biosynthesis; (EC
2.1.1.64) <br>Ubiquinone Biosynthesis-gjo
fig|6666666.60966.peg.2705 CDS 2513079 2512963 -3 - 117
hypothetical protein -none- D23_1c2698 NA
fig|6666666.60966.peg.2706 CDS 2513892 2513197 -3 - 696 Outer
membrane Osmoregulation D23_1c2699 Neut_2508 protein A precursor
fig|6666666.60966.peg.2708 CDS 2514251 2515009 2 + 759 ABC-type
multidrug CBSS-196164.1.peg.1690 D23_1c2700 Neut_2509 transport
system, ATPase component fig|6666666.60966.peg.2709 CDS 2515006
2515752 1 + 747 gliding motility protein -none- D23_1c2701
Neut_2510 GldF fig|6666666.60966.peg.2710 CDS 2515776 2517128 3 +
1353 Mucin 2 precursor -none- D23_1c2702 Neut_2511
fig|6666666.60966.peg.2711 CDS 2517144 2517959 3 + 816
Formamidopyrimidine- DNA Repair Base D23_1c2703 Neut_2512 DNA
glycosylase (EC Excision 3.2.2.23) fig|6666666.60966.peg.2712 CDS
2518479 2517994 -3 - 486 Thioredoxin -none- D23_1c2704 Neut_2513
fig|6666666.60966.peg.2713 CDS 2520458 2518644 -2 - 1815
GTP-binding protein Universal GTPases D23_1c2705 Neut_2514
TypA/BipA fig|6666666.60966.peg.2714 CDS 2520591 2521196 3 + 606
Riboflavin synthase Riboflavin, FMN and FAD D23_1c2706 Neut_2515
eubacterial/eukaryotic metabolism; (EC 2.5.1.9)
<br>Riboflavin, FMN and FAD metabolism in plants;
<br>Riboflavin synthesis cluster; <br>riboflavin to FAD
fig|6666666.60966.peg.2715 CDS 2521193 2522302 2 + 1110
3,4-dihydroxy-2- Riboflavin, FMN and FAD D23_1c2707 Neut_2516
butanone 4-phosphate metabolism; synthase (EC 4.1.99.12)/
<br>Riboflavin, FMN and GTP cyclohydrolase II FAD metabolism;
(EC 3.5.4.25) <br>Riboflavin, FMN and FAD metabolism in
plants; <br>Riboflavin, FMN and FAD metabolism in plants;
<br>Riboflavin synthesis cluster; <br>Riboflavin
synthesis cluster; <br>riboflavin to FAD
fig|6666666.60966.peg.2716 CDS 2522529 2523026 3 + 498
6,7-dimethyl-8- Possible RNA D23_1c2708 Neut_2517 ribityllumazine
synthase degradation cluster; (EC 2.5.1.78) <br>Riboflavin,
FMN and FAD metabolism; <br>Riboflavin, FMN and FAD
metabolism in plants; <br>Riboflavin synthesis cluster
fig|6666666.60966.peg.2717 CDS 2523023 2523526 2 + 504
Transcription Riboflavin synthesis D23_1c2709 Neut_2518 termination
protein cluster; NusB <br>Transcription factors bacterial
fig|6666666.60966.peg.2719 CDS 2523801 2524787 3 + 987 Thiamine-
5-FCL-like protein; D23_1c2710 Neut_2519 monophosphate kinase
<br>Riboflavin synthesis (EC 2.7.4.16) cluster;
<br>Thiamin biosynthesis fig|6666666.60966.peg.2720 CDS
2524864 2525307 1 + 444 Phosphatidylglycerophosphatase Glycerolipid
and D23_1c2711 Neut_2520 A (EC 3.1.3.27) Glycerophospholipid
Metabolism in Bacteria; <br>Riboflavin synthesis cluster
fig|6666666.60966.peg.2721 CDS 2525304 2525846 3 + 543 C-terminal
domain of DNA repair system D23_1c2712 Neut_2521 CinA type S;
Protein including RecA, MutS Implicated in DNA and a hypothetical
repair function with protein; <br>NAD and RecA and MutS NADP
cofactor biosynthesis global; <br>NAD and NADP cofactor
biosynthesis global; <br>Possible RNA degradation cluster;
<br>Riboflavin, FMN and FAD metabolism in plants;
<br>Riboflavin synthesis cluster fig|6666666.60966.peg.2722
CDS 2527502 2526306 -2 - 1197 FIG00859610: -none- D23_1c2713
Neut_2522 hypothetical protein fig|6666666.60966.peg.2723 CDS
2529448 2527829 -1 - 1620 ATP-dependent DNA -none- D23_1c2714
Neut_2523 helicase RecQ fig|6666666.60966.peg.2724 CDS 2529855
2529445 -3 - 411 Ribosome-associated DNA replication cluster
D23_1c2715 Neut_2524 heat shock protein 1; <br>Heat shock
dnaK implicated in the gene cluster extended recycling of the 50S
subunit (S4 paralog) fig|6666666.60966.peg.2725 CDS 2530686 2529877
-3 - 810 InterPro IPR002781 -none- D23_1c2716 Neut_2525 COGs
COG0730 fig|6666666.60966.peg.2726 CDS 2532376 2530694 -1 - 1683
FIG003847: CBSS-269482.4.peg.5018 D23_1c2717 Neut_2526
Oxidoreductase (flavoprotein) fig|6666666.60966.peg.2727 CDS
2532913 2532488 -1 - 426 Transcriptional -none- D23_1c2718
Neut_2527 regulator, ArsR family fig|6666666.60966.peg.2728 CDS
2533377 2532910 -3 - 468 GENE II AND X -none- D23_1c2719 Neut_2528
PROTEINS fig|6666666.60966.peg.2729 CDS 2533835 2533407 -2 - 429
Probable -none- D23_1c2720 Neut_2529 transmembrane protein
fig|6666666.60966.peg.2730 CDS 2533940 2534806 2 + 867 FIG146518:
Zn- CBSS-269482.4.peg.5018 D23_1c2721 Neut_2530 dependent
hydrolases, including glyoxylases fig|6666666.60966.peg.2731 CDS
2535475 2534891 -1 - 585 FIG001587: exported -none- D23_1c2722
Neut_2531 protein fig|6666666.60966.peg.2732 CDS 2537039 2535534 -2
- 1506 FIG00859025: -none- D23_1c2723 Neut_2532 hypothetical
protein fig|6666666.60966.peg.2733 CDS 2537388 2537077 -3 - 312
hypothetical protein -none- D23_1c2724 NA fig|6666666.60966.rna.11
RNA 226254 226324 3 + 71 tRNA-Gly-CCC tRNAs NA NA
fig|6666666.60966.rna.2 RNA 6795 6868 3 + 74 tRNA-Cys-GCA tRNAs NA
NA fig|6666666.60966.rna.39 RNA 1810921 1810848 -1 - 74
tRNA-Gly-TCC -none- NA NA fig|6666666.60966.rna.23 RNA 969765
969839 3 + 75 tRNA-Gln-TTG -none- NA NA fig|6666666.60966.rna.36
RNA 1758968 1759042 2 + 75 tRNA-Val-CAC tRNAs NA NA
fig|6666666.60966.rna.38 RNA 1810812 1810738 -3 - 75 tRNA-Thr-GGT
-none- NA NA fig|6666666.60966.rna.1 RNA 6614 6689 2 + 76
tRNA-Gly-GCC tRNAs NA NA fig|6666666.60966.rna.7 RNA 120428 120503
2 + 76 tRNA-Ala-TGC -none- NA NA fig|6666666.60966.rna.12 RNA
284547 284472 -3 - 76 tRNA-Glu-TTC -none- NA NA
fig|6666666.60966.rna.13 RNA 284648 284573 -2 - 76 tRNA-Ala-GGC
tRNAs NA NA fig|6666666.60966.rna.14 RNA 493566 493641 3 + 76
tRNA-Thr-CGT -none- NA NA fig|6666666.60966.rna.16 RNA 561828
561903 3 + 76 tRNA-Val-TAC -none- NA NA fig|6666666.60966.rna.20
RNA 859357 859282 -1 - 76 tRNA-Lys-TTT -none- NA NA
fig|6666666.60966.rna.21 RNA 948801 948876 3 + 76 tRNA-Thr-TGT
-none- NA NA fig|6666666.60966.rna.24 RNA 1157662 1157587 -1 - 76
tRNA-Arg-CCT -none- NA NA fig|6666666.60966.rna.25 RNA 1199325
1199250 -3 - 76 tRNA-His-GTG -none- NA NA fig|6666666.60966.rna.29
RNA 1470510 1470435 -3 - 76 tRNA-Asn-GTT -none- NA NA
fig|6666666.60966.rna.33 RNA 1618239 1618314 3 + 76 tRNA-Met-CAT
-none- NA NA fig|6666666.60966.rna.34 RNA 1673498 1673423 -2 - 76
tRNA-Arg-CCG tRNAs NA NA fig|6666666.60966.rna.37 RNA 1809438
1809363 -3 - 76 tRNA-Trp-CCA tRNAs NA NA fig|6666666.60966.rna.42
RNA 2107281 2107356 3 + 76 tRNA-Phe-GAA tRNAs NA NA
fig|6666666.60966.rna.6 RNA 120349 120425 1 + 77 tRNA-Ile-GAT
-none- NA NA fig|6666666.60966.rna.10 RNA 196762 196838 1 + 77
tRNA-Met-CAT -none- NA NA fig|6666666.60966.rna.15 RNA 524553
524629 3 + 77 tRNA-Val-GAC tRNAs NA NA fig|6666666.60966.rna.17 RNA
561963 562039 3 + 77 tRNA-Asp-GTC -none- NA NA
fig|6666666.60966.rna.18 RNA 728392 728316 -1 - 77 tRNA-Pro-CGG
tRNAs NA NA fig|6666666.60966.rna.26 RNA 1199452 1199376 -1 - 77
tRNA-Arg-TCT -none- NA NA fig|6666666.60966.rna.27 RNA 1199573
1199497 -2 - 77 tRNA-Pro-TGG -none- NA NA fig|6666666.60966.rna.28
RNA 1427736 1427812 3 + 77 tRNA-Met-CAT -none- NA NA
fig|6666666.60966.rna.41 RNA 2107137 2107213 3 + 77 tRNA-Arg-ACG
tRNAs NA NA fig|6666666.60966.rna.44 RNA 2339644 2339568 -1 - 77
tRNA-Pro-GGG tRNAs NA NA fig|6666666.60966.rna.19 RNA 835520 835604
2 + 85 tRNA-Leu-GAG tRNAs NA NA fig|6666666.60966.rna.32 RNA
1597631 1597715 2 + 85 tRNA-Leu-CAG tRNAs NA NA
fig|6666666.60966.rna.40 RNA 1811116 1811032 -1 - 85 tRNA-Tyr-GTA
-none- NA NA fig|6666666.60966.rna.4 RNA 97072 96987 -1 - 86
tRNA-Leu-TAG -none- NA NA fig|6666666.60966.rna.31 RNA 1574940
1574854 -3 - 87 tRNA-Leu-CAA tRNAs NA NA fig|6666666.60966.rna.30
RNA 1550222 1550135 -2 - 88 tRNA-Ser-TGA -none- NA NA
fig|6666666.60966.rna.3 RNA 6894 6982 3 + 89 tRNA-Leu-TAA -none- NA
NA fig|6666666.60966.rna.22 RNA 956464 956374 -1 - 91 tRNA-Ser-GGA
tRNAs NA NA fig|6666666.60966.rna.35 RNA 1757250 1757342 3 + 93
tRNA-Ser-CGA tRNAs NA NA fig|6666666.60966.rna.43 RNA 2120297
2120205 -2 - 93 tRNA-Ser-GCT -none- NA NA fig|6666666.60966.peg.111
CDS 108515 108628 2 + 114 hypothetical protein -none- NA NA
fig|6666666.60966.peg.353 CDS 326760 326647 -3 - 114 hypothetical
protein -none- NA NA fig|6666666.60966.peg.404 CDS 375917 375804 -2
- 114 hypothetical protein -none- NA NA fig|6666666.60966.peg.432
CDS 397539 397426 -3 - 114 hypothetical protein -none- NA NA
fig|6666666.60966.peg.509 CDS 474482 474369 -2 - 114 hypothetical
protein -none- NA NA fig|6666666.60966.peg.589 CDS 543008 543121 2
+ 114 hypothetical protein -none- NA NA fig|6666666.60966.peg.838
CDS 770105 770218 2 + 114 hypothetical protein -none- NA NA
fig|6666666.60966.peg.923 CDS 855159 855046 -3 - 114 hypothetical
protein -none- NA NA fig|6666666.60966.peg.943 CDS 873193 873306 1
+ 114 hypothetical protein -none- NA NA fig|6666666.60966.peg.1081
CDS 1010260 1010373 1 + 114 hypothetical protein -none- NA NA
fig|6666666.60966.peg.1333 CDS 1235666 1235779 2 + 114 hypothetical
protein -none- NA NA fig|6666666.60966.peg.1414 CDS 1326350 1326463
2 + 114 hypothetical protein -none- NA NA
fig|6666666.60966.peg.1695 CDS 1575540 1575653 3 + 114 hypothetical
protein -none- NA NA fig|6666666.60966.peg.1875 CDS 1749599 1749486
-2 - 114 Mobile element protein -none- NA NA
fig|6666666.60966.peg.2082 CDS 1936491 1936378 -3 - 114
hypothetical protein -none- NA NA fig|6666666.60966.peg.2205 CDS
2047715 2047828 2 + 114 hypothetical protein -none- NA NA
fig|6666666.60966.peg.2370 CDS 2201390 2201277 -2 - 114
hypothetical protein -none- NA NA fig|6666666.60966.peg.2413 CDS
2236764 2236651 -3 - 114 hypothetical protein -none- NA NA
fig|6666666.60966.peg.2577 CDS 2379043 2378930 -1 - 114
hypothetical protein -none- NA NA fig|6666666.60966.peg.421 CDS
392634 392518 -3 - 117 hypothetical protein -none- NA NA
fig|6666666.60966.peg.431 CDS 397234 397350 1 + 117 hypothetical
protein -none- NA NA fig|6666666.60966.peg.1104 CDS 1033773 1033889
3 + 117 hypothetical protein -none- NA NA
fig|6666666.60966.peg.1856 CDS 1730271 1730155 -3 - 117
hypothetical protein -none- NA NA fig|6666666.60966.peg.2044 CDS
1907891 1907775 -2 - 117 hypothetical protein -none- NA NA
fig|6666666.60966.peg.2046 CDS 1908400 1908516 1 + 117 hypothetical
protein -none- NA NA fig|6666666.60966.peg.2250 CDS 2086632 2086516
-3 - 117 hypothetical protein -none- NA NA
fig|6666666.60966.peg.2378 CDS 2209362 2209246 -3 - 117
hypothetical protein -none- NA NA fig|6666666.60966.peg.28 CDS
31960 31841 -1 - 120 hypothetical protein -none- NA NA
fig|6666666.60966.peg.536 CDS 496598 496717 2 + 120 hypothetical
protein -none- NA NA fig|6666666.60966.peg.866 CDS 794273 794392 2
+ 120 hypothetical protein -none- NA NA fig|6666666.60966.peg.1031
CDS 956342 956223 -2 - 120 hypothetical protein -none- NA NA
fig|6666666.60966.peg.1238 CDS 1152349 1152230 -1 - 120
hypothetical protein -none- NA NA fig|6666666.60966.peg.1279 CDS
1184453 1184572 2 + 120 hypothetical protein -none- NA NA
fig|6666666.60966.peg.1566 CDS 1462529 1462410 -2 - 120
hypothetical protein -none- NA NA fig|6666666.60966.peg.1604 CDS
1492079 1491960 -2 - 120 hypothetical protein -none- NA NA
fig|6666666.60966.peg.1610 CDS 1495100 1495219 2 + 120 hypothetical
protein -none- NA NA fig|6666666.60966.peg.1938 CDS 1820165 1820046
-2 - 120 hypothetical protein -none- NA NA
fig|6666666.60966.peg.1940 CDS 1820392 1820511 1 + 120 hypothetical
protein -none- NA NA fig|6666666.60966.peg.2194 CDS 2040715 2040596
-1 - 120 hypothetical protein -none- NA NA
fig|6666666.60966.peg.2229 CDS 2069192 2069073 -2 - 120
hypothetical protein -none- NA NA fig|6666666.60966.peg.2542 CDS
2355482 2355601 2 + 120 hypothetical protein -none- NA NA
fig|6666666.60966.peg.477 CDS 444630 444508 -3 - 123 hypothetical
protein -none- NA NA fig|6666666.60966.peg.634 CDS 579242 579364 2
+ 123 hypothetical protein -none- NA NA fig|6666666.60966.peg.927
CDS 859107 859229 3 + 123 hypothetical protein -none- NA NA
fig|6666666.60966.peg.1015 CDS 941818 941940 1 + 123 hypothetical
protein -none- NA NA fig|6666666.60966.peg.1388 CDS 1298114 1298236
2 + 123 hypothetical protein -none- NA NA
fig|6666666.60966.peg.1755 CDS 1633195 1633073 -1 - 123
hypothetical protein -none- NA NA fig|6666666.60966.peg.2224 CDS
2067753 2067631 -3 - 123 hypothetical protein -none- NA NA
fig|6666666.60966.peg.2271 CDS 2103666 2103788 3 + 123 hypothetical
protein -none- NA NA fig|6666666.60966.peg.2336 CDS 2170340 2170462
2 + 123 hypothetical protein -none- NA NA
fig|6666666.60966.peg.2415 CDS 2237130 2237008 -3 - 123
Hydroxyacylglutathione CBSS-228410.1.peg.134; NA NA hydrolase (EC
3.1.2.6) <br>CBSS- 342610.3.peg.1536; <br>Glutathione:
Non- redox reactions; <br>Methylglyoxal Metabolism
fig|6666666.60966.peg.82 CDS 79801 79676 -1 - 126 hypothetical
protein -none- NA NA fig|6666666.60966.peg.585 CDS 541998 542123 3
+ 126 hypothetical protein -none- NA NA fig|6666666.60966.peg.1268
CDS 1176741 1176866 3 + 126 hypothetical protein -none- NA NA
fig|6666666.60966.peg.1473 CDS 1385674 1385799 1 + 126 hypothetical
protein -none- NA NA fig|6666666.60966.peg.1510 CDS 1423155 1423030
-3 - 126 hypothetical protein -none- NA NA
fig|6666666.60966.peg.1690 CDS 1573599 1573474 -3 - 126
hypothetical protein -none- NA NA fig|6666666.60966.peg.1758 CDS
1635456 1635331 -3 - 126 hypothetical protein -none- NA NA
fig|6666666.60966.peg.1935 CDS 1816227 1816352 3 + 126 hypothetical
protein -none- NA NA fig|6666666.60966.peg.1966 CDS 1832788 1832913
1 + 126 hypothetical protein -none- NA NA
fig|6666666.60966.peg.2285 CDS 2119314 2119439 3 + 126 hypothetical
protein -none- NA NA fig|6666666.60966.peg.21 CDS 28650 28522 -3 -
129 hypothetical protein -none- NA NA fig|6666666.60966.peg.27 CDS
31632 31760 3 + 129 hypothetical protein -none- NA NA
fig|6666666.60966.peg.247 CDS 231537 231665 3 + 129 hypothetical
protein -none- NA NA fig|6666666.60966.peg.300 CDS 272364 272492 3
+ 129 hypothetical protein -none- NA NA fig|6666666.60966.peg.864
CDS 792354 792226 -3 - 129 hypothetical protein -none- NA NA
fig|6666666.60966.peg.1166 CDS 1092637 1092509 -1 - 129
hypothetical protein -none- NA NA fig|6666666.60966.peg.1314 CDS
1216530 1216658 3 + 129 hypothetical protein -none- NA NA
fig|6666666.60966.peg.1730 CDS 1612183 1612311 1 + 129 hypothetical
protein -none- NA NA fig|6666666.60966.peg.2328 CDS 2162434 2162306
-1 - 129 hypothetical protein -none- NA NA
fig|6666666.60966.peg.122 CDS 124194 124063 -3 - 132 hypothetical
protein -none- NA NA fig|6666666.60966.peg.154 CDS 155514 155645 3
+ 132 hypothetical protein -none- NA NA fig|6666666.60966.peg.874
CDS 801546 801677 3 + 132 hypothetical protein -none- NA NA
fig|6666666.60966.peg.894 CDS 823808 823939 2 + 132 hypothetical
protein -none- NA NA fig|6666666.60966.peg.960 CDS 886681 886550 -1
- 132 hypothetical protein -none- NA NA fig|6666666.60966.peg.1188
CDS 1108861 1108730 -1 - 132 hypothetical protein -none- NA NA
fig|6666666.60966.peg.1578 CDS 1468706 1468837 2 + 132 hypothetical
protein -none- NA NA fig|6666666.60966.peg.1950 CDS 1824304 1824435
1 + 132 hypothetical protein -none- NA NA
fig|6666666.60966.peg.1983 CDS 1850338 1850469 1 + 132 hypothetical
protein -none- NA NA fig|6666666.60966.peg.2066 CDS 1923319 1923450
1 + 132 hypothetical protein -none- NA NA
fig|6666666.60966.peg.2445 CDS 2263603 2263472 -1 - 132
hypothetical protein -none- NA NA fig|6666666.60966.peg.2570 CDS
2376200 2376331 2 + 132 hypothetical protein -none- NA NA
fig|6666666.60966.peg.296 CDS 267656 267790 2 + 135 hypothetical
protein -none- NA NA fig|6666666.60966.peg.1086 CDS 1016149 1016015
-1 - 135 hypothetical protein -none- NA NA
fig|6666666.60966.peg.1167 CDS 1092703 1092837 1 + 135 hypothetical
protein -none- NA NA fig|6666666.60966.peg.1560 CDS 1459112 1459246
2 + 135 hypothetical protein -none- NA NA
fig|6666666.60966.peg.1597 CDS 1486647 1486513 -3 - 135
hypothetical protein -none- NA NA fig|6666666.60966.peg.1949 CDS
1824258 1824124 -3 - 135 hypothetical protein -none- NA NA
fig|6666666.60966.peg.2059 CDS 1916861 1916995 2 + 135 hypothetical
protein -none- NA NA fig|6666666.60966.peg.2151 CDS 1995848 1995982
2 + 135 FIG00858674: -none- NA NA hypothetical protein
fig|6666666.60966.peg.2230 CDS 2069201 2069335 2 + 135 hypothetical
protein -none- NA NA fig|6666666.60966.peg.2363 CDS 2194044 2194178
3 + 135 LSU ribosomal protein Cell Division Subsystem NA NA L34p
including YidCD; <br>RNA modification cluster
fig|6666666.60966.peg.2527 CDS 2338623 2338489 -3 - 135
hypothetical protein -none- NA NA fig|6666666.60966.peg.1276 CDS
1182314 1182177 -2 - 138 hypothetical protein -none- NA NA
fig|6666666.60966.peg.1317 CDS 1218021 1218158 3 + 138 hypothetical
protein -none- NA NA fig|6666666.60966.peg.1606 CDS 1493209 1493072
-1 - 138 hypothetical protein -none- NA NA
fig|6666666.60966.peg.1867 CDS 1739233 1739370 1 + 138 Error-prone,
lesion -none- NA NA bypass DNA polymerase V(UmuC)
fig|6666666.60966.peg.2117 CDS 1966387 1966250 -1 - 138
hypothetical protein -none- NA NA fig|6666666.60966.peg.2227 CDS
2068598 2068735 2 + 138 hypothetical protein -none- NA NA
fig|6666666.60966.peg.163 CDS 160970 160830 -2 - 141 hypothetical
protein -none- NA NA fig|6666666.60966.peg.173 CDS 168825 168965 3
+ 141 hypothetical protein -none- NA NA fig|6666666.60966.peg.1286
CDS 1189481 1189621 2 + 141 hypothetical protein -none- NA NA
fig|6666666.60966.peg.1416 CDS 1328534 1328674 2 + 141 hypothetical
protein -none- NA NA fig|6666666.60966.peg.1422 CDS 1330733 1330873
2 + 141 hypothetical protein -none- NA NA
fig|6666666.60966.peg.1759 CDS 1635699 1635839 3 + 141 hypothetical
protein -none- NA NA fig|6666666.60966.peg.1775 CDS 1649712 1649572
-3 - 141 Mobile element protein -none- NA NA
fig|6666666.60966.peg.1984 CDS 1850712 1850572 -3 - 141
hypothetical protein -none- NA NA fig|6666666.60966.peg.2003 CDS
1866906 1867046 3 + 141 hypothetical protein -none- NA NA
fig|6666666.60966.peg.2080 CDS 1935668 1935808 2 + 141 hypothetical
protein -none- NA NA fig|6666666.60966.peg.2487 CDS 2301272 2301132
-2 - 141 hypothetical protein -none- NA NA
fig|6666666.60966.peg.369 CDS 342367 342224 -1 - 144 hypothetical
protein -none- NA NA fig|6666666.60966.peg.635 CDS 579509 579652 2
+ 144 hypothetical protein -none- NA NA fig|6666666.60966.peg.1001
CDS 928837 928980 1 + 144 hypothetical protein -none- NA NA
fig|6666666.60966.peg.1642 CDS 1524746 1524603 -2 - 144
hypothetical protein -none- NA NA fig|6666666.60966.peg.2114 CDS
1962886 1963029 1 + 144 hypothetical protein -none- NA NA
fig|6666666.60966.peg.2593 CDS 2391861 2392004 3 + 144 hypothetical
protein -none- NA NA
fig|6666666.60966.peg.205 CDS 197036 196890 -2 - 147 Integrase
-none- NA NA fig|6666666.60966.peg.284 CDS 260995 261141 1 + 147
hypothetical protein -none- NA NA fig|6666666.60966.peg.1885 CDS
1759287 1759141 -3 - 147 hypothetical protein -none- NA NA
fig|6666666.60966.peg.2453 CDS 2272001 2271855 -2 - 147
hypothetical protein -none- NA NA fig|6666666.60966.peg.2620 CDS
2417974 2417828 -1 - 147 hypothetical protein -none- NA NA
fig|6666666.60966.peg.2623 CDS 2420545 2420399 -1 - 147
hypothetical protein -none- NA NA fig|6666666.60966.peg.108 CDS
106117 106266 1 + 150 hypothetical protein -none- NA NA
fig|6666666.60966.peg.813 CDS 746234 746085 -2 - 150 hypothetical
protein -none- NA NA fig|6666666.60966.peg.1296 CDS 1205130 1205279
3 + 150 hypothetical protein -none- NA NA
fig|6666666.60966.peg.1334 CDS 1235992 1235843 -1 - 150
hypothetical protein -none- NA NA fig|6666666.60966.peg.2300 CDS
2134634 2134485 -2 - 150 hypothetical protein -none- NA NA
fig|6666666.60966.peg.35 CDS 36062 35910 -2 - 153 hypothetical
protein -none- NA NA fig|6666666.60966.peg.1312 CDS 1215961 1216113
1 + 153 hypothetical protein -none- NA NA
fig|6666666.60966.peg.2143 CDS 1990257 1990105 -3 - 153
hypothetical protein -none- NA NA fig|6666666.60966.peg.359 CDS
335237 335392 2 + 156 hypothetical protein -none- NA NA
fig|6666666.60966.peg.546 CDS 506105 505950 -2 - 156 FIG00858972:
-none- NA NA hypothetical protein fig|6666666.60966.peg.1174 CDS
1095978 1095823 -3 - 156 Mobile element protein -none- NA NA
fig|6666666.60966.peg.1384 CDS 1296435 1296280 -3 - 156
hypothetical protein -none- NA NA fig|6666666.60966.peg.2575 CDS
2378324 2378169 -2 - 156 hypothetical protein -none- NA NA
fig|6666666.60966.peg.89 CDS 85217 85059 -2 - 159 hypothetical
protein -none- NA NA fig|6666666.60966.peg.556 CDS 516983 516825 -2
- 159 hypothetical protein -none- NA NA fig|6666666.60966.peg.562
CDS 523304 523462 2 + 159 hypothetical protein -none- NA NA
fig|6666666.60966.peg.1099 CDS 1029431 1029589 2 + 159 hypothetical
protein -none- NA NA fig|6666666.60966.peg.1571 CDS 1466563 1466405
-1 - 159 hypothetical protein -none- NA NA
fig|6666666.60966.peg.613 CDS 562226 562065 -2 - 162 hypothetical
protein -none- NA NA fig|6666666.60966.peg.886 CDS 814562 814401 -2
- 162 hypothetical protein -none- NA NA fig|6666666.60966.peg.1114
CDS 1043720 1043559 -2 - 162 hypothetical protein -none- NA NA
fig|6666666.60966.peg.291 CDS 265661 265825 2 + 165 FIG00856904:
-none- NA NA hypothetical protein fig|6666666.60966.peg.2077 CDS
1934012 1933848 -2 - 165 hypothetical protein -none- NA NA
fig|6666666.60966.peg.620 CDS 568234 568401 1 + 168
Methyltransferase (EC -none- NA NA 2.1.1.--)
fig|6666666.60966.peg.2317 CDS 2149354 2149521 1 + 168 Mobile
element protein -none- NA NA fig|6666666.60966.peg.2420 CDS 2241817
2241650 -1 - 168 hypothetical protein -none- NA NA
fig|6666666.60966.peg.856 CDS 785317 785147 -1 - 171 hypothetical
protein -none- NA NA fig|6666666.60966.peg.1487 CDS 1401876 1401706
-3 - 171 FIG00858878: -none- NA NA hypothetical protein
fig|6666666.60966.peg.2286 CDS 2119703 2119873 2 + 171 hypothetical
protein -none- NA NA fig|6666666.60966.peg.2707 CDS 2514260 2514090
-2 - 171 hypothetical protein -none- NA NA
fig|6666666.60966.peg.862 CDS 790885 790712 -1 - 174 hypothetical
protein -none- NA NA fig|6666666.60966.peg.1450 CDS 1360555 1360382
-1 - 174 Mobile element protein -none- NA NA
fig|6666666.60966.peg.1572 CDS 1466783 1466956 2 + 174 hypothetical
protein -none- NA NA fig|6666666.60966.peg.1608 CDS 1494659 1494835
2 + 177 hypothetical protein -none- NA NA
fig|6666666.60966.peg.2416 CDS 2237303 2237127 -2 - 177
hypothetical protein -none- NA NA fig|6666666.60966.peg.2668 CDS
2479940 2479764 -2 - 177 hypothetical protein -none- NA NA
fig|6666666.60966.peg.748 CDS 694556 694377 -2 - 180 hypothetical
protein -none- NA NA fig|6666666.60966.peg.1667 CDS 1550475 1550296
-3 - 180 hypothetical protein -none- NA NA
fig|6666666.60966.peg.2116 CDS 1965779 1965600 -2 - 180
hypothetical protein -none- NA NA fig|6666666.60966.peg.2144 CDS
1990362 1990541 3 + 180 Mobile element protein -none- NA NA
fig|6666666.60966.peg.2400 CDS 2229074 2228895 -2 - 180
hypothetical protein -none- NA NA fig|6666666.60966.peg.287 CDS
262264 262446 1 + 183 hypothetical protein -none- NA NA
fig|6666666.60966.peg.422 CDS 392649 392831 3 + 183 hypothetical
protein -none- NA NA fig|6666666.60966.peg.1562 CDS 1459862 1460044
2 + 183 hypothetical protein -none- NA NA
fig|6666666.60966.peg.2388 CDS 2218996 2219178 1 + 183 hypothetical
protein -none- NA NA fig|6666666.60966.peg.338 CDS 308508 308323 -3
- 186 hypothetical protein -none- NA NA fig|6666666.60966.peg.1842
CDS 1720173 1719988 -3 - 186 hypothetical protein -none- NA NA
fig|6666666.60966.peg.286 CDS 262147 261959 -1 - 189 hypothetical
protein -none- NA NA fig|6666666.60966.peg.1202 CDS 1125016 1124828
-1 - 189 hypothetical protein -none- NA NA
fig|6666666.60966.peg.1304 CDS 1209919 1209731 -1 - 189
FIG00858878: -none- NA NA hypothetical protein
fig|6666666.60966.peg.2395 CDS 2224520 2224332 -2 - 189
hypothetical protein -none- NA NA fig|6666666.60966.peg.250 CDS
233011 233202 1 + 192 hypothetical protein -none- NA NA
fig|6666666.60966.peg.794 CDS 729662 729471 -2 - 192 hypothetical
protein -none- NA NA fig|6666666.60966.peg.1764 CDS 1639415 1639606
2 + 192 hypothetical protein -none- NA NA fig|6666666.60966.peg.808
CDS 741018 740824 -3 - 195 hypothetical protein -none- NA NA
fig|6666666.60966.peg.276 CDS 255673 255870 1 + 198 Mobile element
protein -none- NA NA fig|6666666.60966.peg.749 CDS 694591 694788 1
+ 198 hypothetical protein -none- NA NA fig|6666666.60966.peg.2718
CDS 2523733 2523536 -1 - 198 hypothetical protein -none- NA NA
fig|6666666.60966.peg.217 CDS 203959 204159 1 + 201 Mobile element
protein -none- NA NA fig|6666666.60966.peg.682 CDS 631759 631959 1
+ 201 FIG00859622: -none- NA NA hypothetical protein
fig|6666666.60966.peg.208 CDS 199189 199392 1 + 204 Cold shock
protein CspA Cold shock, CspA family NA NA of proteins
fig|6666666.60966.peg.380 CDS 348880 348677 -1 - 204 SSU ribosomal
protein -none- NA NA S16p fig|6666666.60966.peg.2149 CDS 1995706
1995503 -1 - 204 dTDP-4- Rhamnose containing NA NA dehydrorhamnose
glycans; <br>dTDP- reductase (EC rhamnose synthesis
1.1.1.133) fig|6666666.60966.peg.1148 CDS 1073050 1073259 1 + 210
hypothetical protein -none- NA NA fig|6666666.60966.peg.2464 CDS
2281343 2281134 -2 - 210 hypothetical protein -none- NA NA
fig|6666666.60966.peg.522 CDS 484104 484316 3 + 213 LSU ribosomal
protein -none- NA NA L29p (L35e) fig|6666666.60966.peg.1481 CDS
1395113 1394901 -2 - 213 hypothetical protein -none- NA NA
fig|6666666.60966.peg.292 CDS 265809 266024 3 + 216 hypothetical
protein -none- NA NA fig|6666666.60966.peg.511 CDS 475254 475469 3
+ 216 SSU ribosomal protein Mycobacterium NA NA S12p (S23e)
virulence operon involved in protein synthesis (SSU ribosomal
proteins); <br>Ribosomal protein S12p Asp
methylthiotransferase fig|6666666.60966.peg.529 CDS 490129 490347 1
+ 219 Translation initiation Translation initiation NA NA factor 1
factors bacterial fig|6666666.60966.peg.2374 CDS 2207422 2207640 1
+ 219 hypothetical protein -none- NA NA fig|6666666.60966.peg.2105
CDS 1956719 1956940 2 + 222 hypothetical protein -none- NA NA
fig|6666666.60966.peg.2690 CDS 2502317 2502538 2 + 222 hypothetical
protein -none- NA NA fig|6666666.60966.peg.2153 CDS 1996354 1996578
1 + 225 hypothetical protein -none- NA NA
fig|6666666.60966.peg.2138 CDS 1985283 1985510 3 + 228 hypothetical
protein -none- NA NA fig|6666666.60966.peg.442 CDS 405529 405299 -1
- 231 hypothetical protein -none- NA NA fig|6666666.60966.peg.1716
CDS 1598000 1597770 -2 - 231 hypothetical protein -none- NA NA
fig|6666666.60966.peg.2439 CDS 2259000 2258770 -3 - 231
hypothetical protein -none- NA NA fig|6666666.60966.peg.1111 CDS
1042874 1043110 2 + 237 Mobile element protein -none- NA NA
fig|6666666.60966.peg.1999 CDS 1865704 1865468 -1 - 237
hypothetical protein -none- NA NA fig|6666666.60966.peg.1214 CDS
1136308 1136069 -1 - 240 hypothetical protein -none- NA NA
fig|6666666.60966.peg.1733 CDS 1614273 1614031 -3 - 243
hypothetical protein -none- NA NA fig|6666666.60966.peg.48 CDS
47253 47498 3 + 246 Alpha-L-Rha alpha-1,3- Rhamnose containing NA
NA L-rhamnosyltransferase glycans (EC 2.4.1.--)
fig|6666666.60966.peg.423 CDS 393586 393338 -1 - 249 Mobile element
protein -none- NA NA fig|6666666.60966.peg.429 CDS 396754 396506 -1
- 249 Transglycosylase- -none- NA NA associated protein
fig|6666666.60966.peg.1147 CDS 1072594 1072842 1 + 249 hypothetical
protein -none- NA NA fig|6666666.60966.peg.1951 CDS 1824656 1824408
-2 - 249 Plasmid stabilization -none- NA NA system protein
fig|6666666.60966.peg.2579 CDS 2380195 2380446 1 + 252 Mobile
element protein -none- NA NA fig|6666666.60966.peg.523 CDS 484294
484548 1 + 255 SSU ribosomal protein -none- NA NA S17p (S11e)
fig|6666666.60966.peg.1022 CDS 948522 948782 3 + 261 Stringent
starvation Carbon Starvation NA NA protein B
fig|6666666.60966.peg.1957 CDS 1826664 1826936 3 + 273 hypothetical
protein -none- NA NA fig|6666666.60966.peg.2273 CDS 2108052 2108336
3 + 285 putative DNA transport -none- NA NA competence protein
fig|6666666.60966.peg.46 CDS 46807 46481 -1 - 327 Conserved domain
-none- NA NA protein fig|6666666.60966.peg.2109 CDS 1959886 1960239
1 + 354 hypothetical protein -none- NA NA
fig|6666666.60966.peg.2429 CDS 2248841 2248488 -2 - 354
hypothetical protein -none- NA NA fig|6666666.60966.peg.1579 CDS
1468834 1469334 1 + 501 hypothetical protein -none- NA NA
fig|6666666.60966.peg.293 CDS 266114 266689 2 + 576 hypothetical
protein -none- NA NA
TABLE-US-00019 SUPPLEMENTARY TABLE 2 Selected D23 sequences SEQ ID
and length Description Sequence SEQ ID amoC1
MATTLGTSSASSVSSRGYDMSLWYDSKFYKFGLITMLLVAIFWVWYQRYF NO: 4 (D23_1c22
AYSHGMDSMEPEFDRVWMGLWRVHMAIMPLFALVTWGWIWKTRDTEEQLN (271 72)
NLDPKLEIKRYFYYMMWLGVYIFGVYWGGSFFTEQDASWHQVIIRDTSFT aa) protein
PSHVVVFYGSFPMYIVCGVATYLYAMTRLPLFHRGISFPLVMAIAGPLMI
LPNVGLNEWGHAFWFMEELFSAPLHWGFVVLGWAGLFQGGVAAQIITRYS
NLTDVVWNNQSKEILNNRVVA SEQ ID amoC1
ATGGCAACTACGTTAGGAACGAGCAGTGCCTCATCAGTCTCATCAAGAGG NO: 5 (D23_1c22
CTATGACATGTCACTGTGGTATGACTCCAAATTTTATAAATTTGGTTTAA (816 72) DNA
TAACCATGTTGTTGGTAGCGATATTCTGGGTATGGTATCAACGTTACTTT nt)
GCCTATTCACACGGAATGGATTCAATGGAACCAGAGTTTGACCGTGTATG
GATGGGCCTGTGGCGTGTGCACATGGCCATTATGCCGCTGTTTGCACTGG
TAACCTGGGGCTGGATCTGGAAAACACGTGATACAGAAGAGCAATTGAAT
AACCTGGATCCGAAACTGGAAATCAAACGCTACTTCTACTACATGATGTG
GCTGGGTGTATACATTTTTGGTGTTTACTGGGGTGGTAGCTTCTTTACGG
AGCAAGATGCCTCCTGGCACCAGGTGATTATTCGTGACACCAGCTTTACA
CCAAGTCACGTAGTCGTGTTTTATGGATCATTTCCGATGTACATCGTCTG
CGGAGTTGCAACCTATCTGTATGCAATGACCCGTCTGCCGCTGTTTCATC
GTGGAATTTCTTTCCCACTGGTGATGGCGATTGCAGGTCCTCTGATGATT
CTGCCAAACGTTGGTCTGAATGAATGGGGTCATGCTTTCTGGTTCATGGA
AGAGCTGTTCAGCGCACCGCTGCATTGGGGTTTTGTAGTGCTCGGTTGGG
CTGGGTTATTCCAGGGTGGAGTTGCTGCCCAAATCATTACCCGTTATTCC
AACCTGACTGACGTGGTCTGGAATAATCAAAGCAAAGAAATTCTGAATAA CCGGGTTGTAGCTTAG
SEQ ID amoA1 VSIFRTEEILKAAKMPPEAVHMSRLIDAVYFPILVVLLVGTYHMHFMLLA NO:
6 (D23_1c22 GDWDFWMDWKDRQWWPVVTPIVGITYCSAIMYYLWVNYRQPFGATLCVVC (276
71) LLIGEWLTRYWGFYWWSHYPLNFVTPGIMLPGALMLDFTMYLTRNWLVTA aa) protein
LVGGGFFGLLFYPGNWAIFGPTHLPIVVEGTLLSMADYMGHLYVRTGTPE
YVRHIEQGSLRTFGGHTTVIAAFFAAFVSMLMFAVWWYLGKVYCTAFFYV
KGKRGRIVQRNDVTAFGEEGFPEGIK SEQ ID amoA1
GTGAGTATATTTAGAACAGAAGAGATCCTGAAAGCGGCCAAGATGCCGCC NO: 7 (D23_1c22
GGAAGCGGTCCATATGTCACGCCTGATTGATGCGGTTTATTTTCCGATTC (831 71) DNA
TGGTTGTTCTGTTGGTAGGTACCTACCATATGCACTTCATGTTGTTGGCA nt)
GGTGACTGGGATTTCTGGATGGACTGGAAAGATCGTCAATGGTGGCCTGT
AGTAACACCTATTGTAGGCATTACCTATTGCTCGGCAATTATGTATTACC
TGTGGGTCAACTACCGTCAACCATTTGGTGCGACTCTGTGCGTAGTGTGT
TTGCTGATAGGTGAGTGGCTGACACGTTACTGGGGTTTCTACTGGTGGTC
ACACTATCCACTCAATTTTGTAACCCCAGGTATCATGCTCCCGGGTGCAT
TGATGTTGGATTTCACAATGTATCTGACACGTAACTGGTTGGTGACTGCA
TTGGTTGGGGGTGGATTCTTTGGTCTGCTGTTTTACCCGGGTAACTGGGC
AATCTTTGGTCCGACCCATCTGCCAATCGTTGTAGAAGGAACACTGTTGT
CGATGGCTGACTATATGGGTCACCTGTATGTTCGTACGGGTACACCTGAG
TATGTTCGTCATATTGAACAAGGTTCATTACGTACCTTTGGTGGTCACAC
CACAGTTATTGCAGCATTCTTCGCTGCGTTTGTATCCATGCTGATGTTTG
CAGTCTGGTGGTATCTTGGAAAAGTTTACTGCACAGCCTTCTTCTACGTT
AAAGGTAAAAGAGGACGTATCGTGCAGCGCAATGATGTTACGGCATTTGG
TGAAGAAGGGTTTCCAGAGGGGATCAAATAA SEQ ID amoB1
MGIKNLYKRGMMGLCGVAVYAMAALTMTVTLDVSTVAAHGERSQEPFLRM NO: 8 (D23_1c22
RTVQWYDVKWGPEVTKVNENAQITGKFHLAEDWPRAAARPDFAFFNVGSP (421 70)
SSVYVRLSTKINGHPWFISGPLQIGRDYAFEVQLRARIPGRHHMHAMLNV aa) protein
KDAGPIAGPGAWMNITGSWDDFTNPLKLLTGETIDSETFNLSNGIFWHIL
WMSIGIFWIGIFVARPMFLPRSRVLLAYGDDLLLDPMDKKITWVLAILTL
AIVWGGYRYTETKHPYTVPIQAGQSKVAPLPVAPNPVAIKITDANYDVPG
RALRVSMEVTNNGDTPVTFGEFTTAGIRFVNSTGRKYLDPQYPRELVAVG
LNFDDDGAIQPGETKQLRMEAKDALWEIQRLMALLGDPESRFGGLLMSWD
SEGNRHINSIAGPVIPVFTKL SEQ ID amoB1
ATGGGTATCAAGAACCTTTATAAACGTGGAATGATGGGACTTTGTGGCGT NO: 9 (D23_1c22
TGCTGTTTATGCAATGGCGGCACTGACCATGACAGTGACACTAGATGTCT (1266 70) DNA
CAACAGTAGCAGCCCATGGAGAACGATCCCAGGAACCGTTTCTTCGGATG nt)
CGTACAGTACAGTGGTACGATGTTAAGTGGGGTCCGGAAGTAACCAAAGT
CAATGAGAATGCCCAAATTACCGGCAAATTTCACTTGGCTGAAGACTGGC
CGCGTGCGGCAGCAAGACCGGATTTCGCATTCTTTAACGTAGGTAGCCCA
AGCTCGGTATACGTGCGTTTGAGTACGAAGATTAATGGCCACCCATGGTT
TATTTCAGGTCCGCTGCAAATTGGTCGTGACTATGCGTTCGAAGTTCAGC
TGAGAGCACGTATTCCAGGACGCCATCACATGCACGCCATGTTAAACGTT
AAAGATGCAGGTCCAATTGCAGGACCGGGTGCATGGATGAACATTACCGG
AAGCTGGGATGATTTTACTAATCCACTCAAGCTGCTGACAGGCGAAACAA
TTGACTCAGAAACATTCAACCTGTCAAACGGTATTTTCTGGCATATTCTC
TGGATGTCAATTGGTATATTTTGGATTGGTATCTTTGTAGCGCGTCCGAT
GTTCCTGCCACGTAGCCGGGTATTGCTCGCTTATGGTGATGATCTGTTGC
TGGATCCGATGGATAAGAAAATCACCTGGGTACTTGCAATCCTGACCTTG
GCTATAGTATGGGGTGGATACCGCTATACAGAAACCAAGCATCCATACAC
AGTACCTATCCAGGCTGGTCAATCCAAAGTTGCACCATTACCGGTAGCAC
CAAATCCGGTAGCAATCAAAATTACAGATGCTAACTATGACGTACCGGGA
CGTGCACTGCGTGTATCGATGGAAGTAACCAACAACGGTGATACACCAGT
CACATTTGGTGAATTTACCACAGCAGGTATTCGTTTCGTTAACAGTACCG
GCCGCAAGTACCTGGATCCACAGTATCCTCGTGAACTGGTTGCAGTAGGC
TTGAATTTTGATGATGATGGTGCAATTCAGCCAGGCGAGACCAAGCAATT
GAGGATGGAAGCCAAAGATGCTCTGTGGGAAATCCAACGTCTGATGGCGT
TGCTGGGTGACCCGGAAAGCCGTTTTGGTGGACTGTTAATGTCTTGGGAT
TCAGAAGGTAATCGCCATATCAACAGTATTGCTGGTCCGGTGATTCCAGT CTTTACCAAGCTCTAA
SEQ ID amoC2 MATTLGTSSASSVSSRGYDMSLWYDSKFYKFGLITMLLVAIFWVWYQRYF NO:
10 (D23_1c25 AYSHGMDSMEPEFDRVWMGLWRVHMAIMPLFALVTWGWIWKTRDTEEQLN
(271 12) NLDPKLEIKRYFYYMMWLGVYIFGVYWGGSFFTEQDASWHQVIIRDTSFT aa)
protein PSHVVVFYGSFPMYIVCGVATYLYAMTRLPLFHRGISFPLVMAIAGPLMI
LPNVGLNEWGHAFWFMEELFSAPLHWGFVVLGWAGLFQGGVAAQIITRYS
NLTDVVWNNQSKEILNNRVVA SEQ ID amoC2
ATGGCAACTACGTTAGGAACGAGCAGTGCCTCATCAGTCTCATCAAGAGG NO: 11 (D23_1c25
CTATGACATGTCACTGTGGTATGACTCCAAATTTTATAAATTTGGTTTAA (816 12) DNA
TAACCATGTTGTTGGTAGCGATATTCTGGGTATGGTATCAACGTTACTTT nt)
GCCTATTCACACGGAATGGATTCAATGGAACCAGAGTTTGACCGTGTATG
GATGGGCCTGTGGCGTGTGCACATGGCCATTATGCCGCTGTTTGCACTGG
TAACCTGGGGCTGGATCTGGAAAACACGTGATACAGAAGAGCAATTGAAT
AACCTGGATCCGAAACTGGAAATCAAACGCTACTTCTACTACATGATGTG
GCTGGGTGTATACATTTTTGGTGTTTACTGGGGTGGTAGCTTCTTTACGG
AGCAAGATGCCTCCTGGCACCAGGTGATTATTCGTGACACCAGCTTTACA
CCAAGTCACGTAGTCGTGTTTTATGGATCATTTCCGATGTACATCGTCTG
CGGAGTTGCAACCTATCTGTATGCAATGACCCGTCTGCCGCTGTTTCATC
GTGGAATTTCTTTCCCACTGGTGATGGCGATTGCAGGTCCTCTGATGATT
CTGCCAAACGTTGGTCTGAATGAATGGGGTCATGCTTTCTGGTTCATGGA
AGAGCTGTTCAGCGCACCGCTGCATTGGGGTTTTGTAGTGCTCGGTTGGG
CTGGGTTATTCCAGGGTGGAGTTGCTGCCCAAATCATTACCCGTTATTCC
AACCTGACTGACGTGGTCTGGAATAATCAAAGCAAAGAAATTCTGAATAA CCGGGTTGTAGCTTAG
SEQ ID amoA2 VSIFRTEEILKAAKMPPEAVHMSRLIDAVYFPILVVLLVGTYHMHFMLLA NO:
12 (D23_1c25 GDWDFWMDWKDRQWWPVVTPIVGITYCSAIMYYLWVNYRQPFGATLCVVC
(276 11) LLIGEWLTRYWGFYWWSHYPLNFVTPGIMLPGALMLDFTMYLTRNWLVTA aa)
protein LVGGGFFGLLFYPGNWAIFGPTHLPIVVEGTLLSMADYMGHLYVRTGTPE
YVRHIEQGSLRTFGGHTTVIAAFFAAFVSMLMFAVWWYLGKVYCTAFFYV
KGKRGRIVQRNDVTAFGEEGFPEGIK SEQ ID amoA2
GTGAGTATATTTAGAACAGAAGAGATCCTGAAAGCGGCCAAGATGCCGCC NO: 13 (D23_1c25
GGAAGCGGTCCATATGTCACGCCTGATTGATGCGGTTTATTTTCCGATTC (831 11) DNA
TGGTTGTTCTGTTGGTAGGTACCTACCATATGCACTTCATGTTGTTGGCA nt)
GGTGACTGGGATTTCTGGATGGACTGGAAAGATCGTCAATGGTGGCCTGT
AGTAACACCTATTGTAGGCATTACCTATTGCTCGGCAATTATGTATTACC
TGTGGGTCAACTACCGTCAACCATTTGGTGCGACTCTGTGCGTAGTGTGT
TTGCTGATAGGTGAGTGGCTGACACGTTACTGGGGTTTCTACTGGTGGTC
ACACTATCCACTCAATTTTGTAACCCCAGGTATCATGCTCCCGGGTGCAT
TGATGTTGGATTTCACAATGTATCTGACACGTAACTGGTTGGTGACTGCA
TTGGTTGGGGGTGGATTCTTTGGTCTGCTGTTTTACCCGGGTAACTGGGC
AATCTTTGGTCCGACCCATCTGCCAATCGTTGTAGAAGGAACACTGTTGT
CGATGGCTGACTATATGGGTCACCTGTATGTTCGTACGGGTACACCTGAG
TATGTTCGTCATATTGAACAAGGTTCATTACGTACCTTTGGTGGTCACAC
CACAGTTATTGCAGCATTCTTCGCTGCGTTTGTATCCATGCTGATGTTTG
CAGTCTGGTGGTATCTTGGAAAAGTTTACTGCACAGCCTTCTTCTACGTT
AAAGGTAAAAGAGGACGTATCGTGCAGCGCAATGATGTTACGGCATTTGG
TGAAGAAGGGTTTCCAGAGGGGATCAAATAA SEQ ID amoB2
MGIKNLYKRGMMGLCGVAVYAMAALTMTVTLDVSTVAAHGERSQEPFLRM NO: 14 (D23_1c25
RTVQWYDVKWGPEVTKVNENAQITGKFHLAEDWPRAAARPDFAFFNVGSP (421 10)
SSVYVRLSTKINGHPWFISGPLQIGRDYAFEVQLRARIPGRHHMHAMLNV aa) protein
KDAGPIAGPGAWMNITGSWDDFTNPLKLLTGETIDSETFNLSNGIFWHIL
WMSIGIFWIGIFVARPMFLPRSRVLLAYGDDLLLDPMDKKITWVLAILTL
AIVWGGYRYTETKHPYTVPIQAGQSKVAPLPVAPNPVAIKITDANYDVPG
RALRVSMEVTNNGDTPVTFGEFTTAGIRFVNSTGRKYLDPQYPRELVAVG
LNFDDDGAIQPGETKQLRMEAKDALWEIQRLMALLGDPESRFGGLLMSWD
SEGNRHINSIAGPVIPVFTKL SEQ ID amoB2
ATGGGTATCAAGAACCTTTATAAACGTGGAATGATGGGACTTTGTGGCGT NO: 15 (D23_1c25
TGCTGTTTATGCAATGGCGGCACTGACCATGACAGTGACACTAGATGTCT (1266 10) DNA
CAACAGTAGCAGCCCATGGAGAACGATCCCAGGAACCGTTTCTTCGGATG nt)
CGTACAGTACAGTGGTACGATGTTAAGTGGGGTCCGGAAGTAACCAAAGT
CAATGAGAATGCCCAAATTACCGGCAAATTTCACTTGGCTGAAGACTGGC
CGCGTGCGGCAGCAAGACCGGATTTCGCATTCTTTAACGTAGGTAGCCCA
AGCTCGGTATACGTGCGTTTGAGTACGAAGATTAATGGCCACCCATGGTT
TATTTCAGGTCCGCTGCAAATTGGTCGTGACTATGCGTTCGAAGTTCAGC
TGAGAGCACGTATTCCAGGACGCCATCACATGCACGCCATGTTAAACGTT
AAAGATGCAGGTCCAATTGCAGGACCGGGTGCATGGATGAACATTACCGG
AAGCTGGGATGATTTTACTAATCCACTCAAGCTGCTGACAGGCGAAACAA
TTGACTCAGAAACATTCAACCTGTCAAACGGTATTTTCTGGCATATTCTC
TGGATGTCAATTGGTATATTTTGGATTGGTATCTTTGTAGCGCGTCCGAT
GTTCCTGCCACGTAGCCGGGTATTGCTCGCTTATGGTGATGATCTGTTGC
TGGATCCGATGGATAAGAAAATCACCTGGGTACTTGCAATCCTGACCTTG
GCTATAGTATGGGGTGGATACCGCTATACAGAAACCAAGCATCCATACAC
AGTACCTATCCAGGCTGGTCAATCCAAAGTTGCACCATTACCGGTAGCAC
CAAATCCGGTAGCAATCAAAATTACAGATGCTAACTATGACGTACCGGGA
CGTGCACTGCGTGTATCGATGGAAGTAACCAACAACGGTGATACACCAGT
CACATTTGGTGAATTTACCACAGCAGGTATTCGTTTCGTTAACAGTACCG
GCCGCAAGTACCTGGATCCACAGTATCCTCGTGAACTGGTTGCAGTAGGC
TTGAATTTTGATGATGATGGTGCAATTCAGCCAGGCGAGACCAAGCAATT
GAGGATGGAAGCCAAAGATGCTCTGTGGGAAATCCAACGTCTGATGGCGT
TGCTGGGTGACCCGGAAAGCCGTTTTGGTGGACTGTTAATGTCTTGGGAT
TCAGAAGGTAATCGCCATATCAACAGTATTGCTGGTCCGGTGATTCCAGT CTTTACCAAGCTCTAA
SEQ ID amoC3 MATNILKDKAAQQVADKPTYDKSEWFDAKYYKFGLLPILAVAVMWVYFQR NO:
16 (D23_1c16 TYAYSHGMDSMEPEFDRIWMGLWRVQMAALPLIALFTWGWLYKTRNTAEQ
(274 05) LANLTPKQEIKRYFYFLMWLGVYIFAVYWGSSFFTEQDASWHQVIIRDTS aa)
protein FTPSHIPLFYGSFPVYIIMGVSMIIYANTRLPLYNKGWSFPLIMTVAGPL
MSLPNVGLNEWGHAFWFMEELFSAPLHWGFVILAWAALFQGGLAVQIIAR
FSNLLDVEWNKQDRAILDDVVTAP SEQ ID amoC3
ATGGCTACAAATATATTAAAAGACAAAGCTGCACAGCAGGTTGCTGATAA NO: 17 (D23_1c16
ACCAACTTATGATAAATCCGAGTGGTTTGATGCTAAATACTATAAATTCG (825 05) DNA
GGCTGCTACCTATCTTAGCTGTAGCTGTGATGTGGGTTTATTTCCAGCGC nt)
ACATACGCCTATTCTCACGGCATGGATTCAATGGAACCGGAATTTGACCG
GATCTGGATGGGCTTGTGGCGTGTTCAAATGGCCGCTCTGCCTCTTATAG
CACTTTTTACGTGGGGATGGTTATATAAAACCCGCAATACTGCAGAACAG
CTTGCCAATCTGACTCCAAAGCAGGAAATAAAGCGGTATTTCTATTTCCT
CATGTGGCTTGGGGTCTATATATTTGCAGTTTACTGGGGATCAAGCTTCT
TTACCGAGCAGGACGCTTCATGGCACCAGGTGATTATCAGGGATACAAGT
TTTACTCCTAGCCATATTCCTCTGTTTTATGGTTCATTCCCGGTATACAT
CATCATGGGAGTATCGATGATTATTTACGCCAACACCCGGTTGCCGCTGT
ACAACAAAGGGTGGTCATTCCCTCTGATCATGACCGTAGCAGGACCGTTG
ATGAGTCTGCCTAACGTTGGCCTGAACGAGTGGGGACACGCCTTCTGGTT
CATGGAAGAACTTTTCAGCGCACCGCTGCACTGGGGCTTCGTGATTCTGG
CTTGGGCTGCCCTGTTCCAGGGTGGGCTTGCAGTACAGATCATAGCTCGC
TTTTCCAACTTGCTTGACGTGGAGTGGAATAAACAAGACAGAGCCATATT
GGACGATGTCGTAACTGCTCCTTAA SEQ ID hao1
MRLGEYLKGMLLCAGLLLIGPVQADISTVPDETYEALKLDRSKATPKETY NO: 18 (D23_1c25
DALVKRYKDPAHGAGKGTMGDYWEPIALSIYMDPSTFYKPPVSPKEIAER (570 29)
KDCVECHSDETPVWVRAWKRSTHANLDKIRNLKPEDPLFYKKGKLEEVEN aa) protein
NLRSMGKLGEKEALKEVGCIDCHVDINAKKKADHTKDVRMPTADVCGTCH
LREFAERESERDTMIWPNGQWPDGRPSHALDYTANIETTVWAAMPQREVA
EGCTMCHTNQNKCDNCHTRHEFSAAESRKPEACATCHSGVDHNNYEAYIM
SKHGKLAEMNRENWNWNVRLKDAFSKGGQTAPTCAACHMEYEGEYTHNIT
RKTRWANYPFVPGIAENITSDWSEARLDSWVVTCTQCHSERFARSYLDLM
DKGTLEGLAKYQEANAIVHKMYEDGTLTGQKTNRPNPPAPEKPGFGIFTQ
LFWSKGNNPASLELKVLEMAENNLAKMHVGLAHVNPGGWTYTEGWGPMNR
AYVEIQDEYTKMQEMTALQARVNKLEGKKTSLLDLKGAGEKISLGGLGGG
MLLAGAIALIGWRKRKQTQA SEQ ID hao1
ATGAGATTAGGGGAGTATTTGAAGGGGATGCTGCTGTGTGCGGGCCTGTT NO: 19 (D23_1c25
GTTGATTGGGCCGGTACAGGCGGATATATCGACGGTACCGGATGAGACGT (1713 29) DNA
ATGAAGCATTGAAGCTGGATCGCAGCAAAGCCACGCCGAAAGAGACCTAT nt)
GATGCGCTGGTGAAGCGTTACAAGGATCCTGCACATGGTGCTGGCAAGGG
CACGATGGGAGACTACTGGGAACCGATAGCGCTTAGTATCTACATGGACC
CGAGCACCTTTTACAAACCACCGGTTTCCCCGAAAGAAATTGCTGAGCGC
AAAGACTGCGTTGAATGCCACTCTGATGAAACGCCGGTTTGGGTAAGAGC
ATGGAAACGCAGCACCCACGCCAACCTGGACAAAATACGCAACCTCAAGC
CGGAAGATCCGCTTTTTTACAAAAAAGGCAAGCTGGAAGAAGTTGAGAAC
AACCTGCGCTCCATGGGCAAACTTGGAGAGAAGGAAGCGCTCAAGGAAGT
AGGCTGTATTGACTGTCACGTTGACATCAACGCCAAAAAGAAAGCAGATC
ACACCAAAGACGTACGCATGCCTACAGCTGACGTTTGCGGAACCTGTCAC
CTGAGAGAATTTGCCGAGCGTGAATCCGAGCGTGACACCATGATCTGGCC
GAATGGCCAGTGGCCTGACGGACGTCCATCCCACGCACTGGACTACACAG
CCAACATTGAAACCACCGTTTGGGCAGCCATGCCGCAACGTGAAGTGGCA
GAAGGTTGCACCATGTGCCACACCAACCAGAACAAATGCGACAACTGCCA
TACCCGCCATGAATTTTCGGCGGCAGAATCCCGCAAACCGGAAGCCTGTG
CCACCTGTCACAGCGGCGTGGATCATAATAACTATGAAGCCTACATTATG
TCCAAGCACGGCAAACTGGCTGAAATGAACCGGGAGAACTGGAACTGGAA
TGTTCGTCTGAAAGACGCCTTCTCCAAAGGAGGTCAGACCGCACCGACCT
GTGCAGCCTGCCACATGGAATACGAAGGGGAATATACCCATAACATCACC
CGTAAGACCCGCTGGGCAAACTACCCGTTTGTTCCGGGGATTGCAGAAAA
CATCACCAGCGACTGGTCAGAAGCTCGTCTGGATTCCTGGGTTGTGACCT
GTACCCAATGTCACTCGGAACGGTTTGCCCGCTCCTACCTGGATCTCATG
GACAAAGGTACCCTGGAAGGGTTGGCTAAATACCAGGAAGCCAATGCCAT
TGTTCACAAAATGTATGAAGACGGCACCCTGACTGGTCAAAAAACCAATC
GTCCGAATCCACCGGCGCCAGAGAAACCGGGTTTTGGTATCTTCACCCAA
CTGTTCTGGTCCAAGGGTAACAACCCGGCCTCACTTGAACTGAAAGTGCT
GGAAATGGCAGAAAACAACCTGGCCAAAATGCACGTAGGACTGGCACACG
TTAATCCAGGTGGCTGGACATATACCGAAGGTTGGGGCCCGATGAACCGT
GCCTATGTTGAAATCCAGGATGAATACACCAAGATGCAGGAAATGACAGC
TCTGCAAGCGCGTGTTAACAAACTGGAAGGTAAAAAAACCAGCCTGCTTG
ACCTCAAGGGAGCGGGAGAAAAGATCTCGCTGGGAGGACTGGGAGGTGGC
ATGTTGCTGGCGGGAGCGATTGCTCTGATTGGCTGGCGTAAACGTAAGCA AACGCAAGCTTGA
SEQ ID hao2 MRLGEYLKGMLLCAGLLLIGPVQADISTVPDETYEALKLDRSKATPKETY NO:
20 (D23_1c19 DALVKRYKDPAHGAGKGTMGDYWEPIALSIYMDPSTFYKPPVSPKEIAER
(570 26) KDCVECHSDETPVWVRAWKRSTHANLDKIRNLKPEDPLFYKKGKLEEVEN aa)
protein NLRSMGKLGEKEALKEVGCIDCHVDINAKKKADHTKDVRMPTADVCGTCH
LREFAERESERDTMIWPNGQWPDGRPSHALDYTANIETTVWAAMPQREVA
EGCTMCHTNQNKCDNCHTRHEFSAAESRKPEACATCHSGVDHNNYEAYIM
SKHGKLAEMNRENWNWNVRLKDAFSKGGQTAPTCAACHMEYEGEYTHNIT
RKTRWANYPFVPGIAENITSDWSEARLDSWVVTCTQCHSERFARSYLDLM
DKGTLEGLAKYQEANAIVHKMYEDGTLTGQKTNRPNPPAPEKPGFGIFTQ
LFWSKGNNPASLELKVLEMAENNLAKMHVGLAHVNPGGWTYTEGWGPMNR
AYVEIQDEYTKMQEMTALQARVNKLEGKKTSLLDLKGAGEKISLGGLGGG
MLLAGAIALIGWRKRKQTQA SEQ ID hao2
ATGAGATTAGGGGAGTATTTGAAGGGGATGCTGCTGTGTGCGGGCCTGTT NO: 21 (D23_1c19
GTTGATTGGGCCGGTACAGGCGGATATATCGACGGTACCGGATGAGACGT (1713 26) DNA
ATGAAGCATTGAAGCTGGATCGCAGCAAAGCCACGCCGAAAGAGACCTAT nt)
GATGCGCTGGTGAAGCGTTACAAGGATCCTGCACATGGTGCTGGCAAGGG
CACGATGGGAGACTACTGGGAACCGATAGCGCTTAGTATCTACATGGACC
CGAGCACCTTTTACAAACCACCGGTTTCCCCGAAAGAAATTGCTGAGCGC
AAAGACTGCGTTGAATGCCACTCTGATGAAACGCCGGTTTGGGTAAGAGC
ATGGAAACGCAGCACCCACGCCAACCTGGACAAAATACGCAACCTCAAGC
CGGAAGATCCGCTTTTTTACAAAAAAGGCAAGCTGGAAGAAGTTGAGAAC
AACCTGCGCTCCATGGGCAAACTTGGAGAGAAGGAAGCGCTCAAGGAAGT
AGGCTGTATTGACTGTCACGTTGACATCAACGCCAAAAAGAAAGCAGATC
ACACCAAAGACGTACGCATGCCTACAGCTGACGTTTGCGGAACCTGTCAC
CTGAGAGAATTTGCCGAGCGTGAATCCGAGCGTGACACCATGATCTGGCC
GAATGGCCAGTGGCCTGACGGACGTCCATCCCACGCACTGGACTACACAG
CCAACATTGAAACCACCGTTTGGGCAGCCATGCCGCAACGTGAAGTGGCA
GAAGGTTGCACCATGTGCCACACCAACCAGAACAAATGCGACAACTGCCA
TACCCGCCATGAATTTTCGGCGGCAGAATCCCGCAAACCGGAAGCCTGTG
CCACCTGTCACAGCGGCGTGGATCATAATAACTATGAAGCCTACATTATG
TCCAAGCACGGCAAACTGGCTGAAATGAACCGGGAGAACTGGAACTGGAA
TGTTCGTCTGAAAGACGCCTTCTCCAAAGGAGGTCAGACCGCACCGACCT
GTGCAGCCTGCCACATGGAATACGAAGGGGAATATACCCATAACATCACC
CGTAAGACCCGCTGGGCAAACTACCCGTTTGTTCCGGGGATTGCAGAAAA
CATCACCAGCGACTGGTCAGAAGCTCGTCTGGATTCCTGGGTTGTGACCT
GTACCCAATGTCACTCGGAACGGTTTGCCCGCTCCTACCTGGATCTCATG
GACAAAGGTACCCTGGAAGGGTTGGCTAAATACCAGGAAGCCAATGCCAT
TGTTCACAAAATGTATGAAGACGGCACCCTGACTGGTCAAAAAACCAATC
GTCCGAATCCACCGGCGCCAGAGAAACCGGGTTTTGGTATCTTCACCCAA
CTGTTCTGGTCCAAGGGTAACAACCCGGCCTCACTTGAACTGAAAGTGCT
GGAAATGGCAGAAAACAACCTGGCCAAAATGCACGTAGGACTGGCACACG
TTAATCCAGGTGGCTGGACATATACCGAAGGTTGGGGCCCGATGAACCGT
GCCTATGTTGAAATCCAGGATGAATACACCAAGATGCAGGAAATGACAGC
TCTGCAAGCGCGTGTTAACAAACTGGAAGGTAAAAAAACCAGCCTGCTTG
ACCTCAAGGGAGCGGGAGAAAAGATCTCGCTGGGAGGACTGGGAGGTGGC
ATGTTGCTGGCGGGAGCGATTGCTCTGATTGGCTGGCGTAAACGTAAGCA AACGCAAGCTTGA
SEQ ID hao3 MRLGEYLKGMLLCAGLLLIGPVQADISTVPDETYEALKLDRSKATPKETY NO:
22 (D23_1c17 DALVKRYKDPAHGAGKGTMGDYWEPIALSIYMDPSTFYKPPVSPKEIAER
(570 88) KDCVECHSDETPVWVRAWKRSTHANLDKIRNLKPEDPLFYKKGKLEEVEN aa)
protein NLRSMGKLGEKEALKEVGCIDCHVDINAKKKADHTKDVRMPTADVCGTCH
LREFAERESERDTMIWPNGQWPDGRPSHALDYTANIETTVWAAMPQREVA
EGCTMCHTNQNKCDNCHTRHEFSAAESRKPEACATCHSGVDHNNYEAYIM
SKHGKLAEMNRENWNWNVRLKDAFSKGGQTAPTCAACHMEYEGEYTHNIT
RKTRWANYPFVPGIAENITSDWSEARLDSWVVTCTQCHSERFARSYLDLM
DKGTLEGLAKYQEANAIVHKMYEDGTLTGQKTNRPNPPAPEKPGFGIFTQ
LFWSKGNNPASLELKVLEMAENNLAKMHVGLAHVNPGGWTYTEGWGPMNR
AYVEIQDEYTKMQEMTALQARVNKLEGKKTSLLDLKGAGEKISLGGLGGG
MLLAGAIALIGWRKRKQTQA SEQ ID hao3
ATGAGATTAGGGGAGTATTTGAAGGGGATGCTGCTGTGTGCGGGCCTGTT NO: 23 (D23_1c17
GTTGATTGGGCCGGTACAGGCGGATATATCGACGGTACCGGATGAGACGT (1713 88) DNA
ATGAAGCATTGAAGCTGGATCGCAGCAAAGCCACGCCGAAAGAGACCTAT nt)
GATGCGCTGGTGAAGCGTTACAAGGATCCTGCGCATGGTGCTGGCAAGGG
CACGATGGGAGACTACTGGGAACCGATAGCGCTTAGTATCTACATGGACC
CGAGCACCTTTTACAAACCACCGGTTTCCCCGAAAGAAATTGCTGAGCGC
AAAGACTGCGTTGAATGCCACTCTGATGAAACGCCGGTTTGGGTAAGAGC
ATGGAAACGCAGCACCCACGCCAACCTGGACAAAATACGCAACCTCAAGC
CGGAAGATCCGCTTTTTTACAAAAAAGGCAAGCTGGAAGAAGTTGAGAAC
AACCTGCGCTCCATGGGCAAACTTGGAGAGAAGGAAGCGCTCAAGGAAGT
AGGCTGTATTGACTGTCACGTTGACATCAACGCCAAAAAGAAAGCAGATC
ACACCAAAGACGTACGCATGCCTACAGCTGACGTTTGCGGAACCTGTCAC
CTGAGAGAATTTGCCGAGCGTGAATCCGAGCGTGACACCATGATCTGGCC
GAATGGCCAGTGGCCTGACGGACGTCCATCCCACGCACTGGACTACACAG
CCAACATTGAAACCACCGTTTGGGCAGCCATGCCGCAACGTGAAGTGGCA
GAAGGTTGCACCATGTGCCACACCAACCAGAACAAATGCGACAACTGCCA
TACCCGCCATGAATTTTCGGCGGCAGAATCCCGCAAACCGGAAGCCTGTG
CCACCTGTCACAGCGGCGTGGATCATAATAACTATGAAGCCTACATTATG
TCCAAGCACGGCAAACTGGCTGAAATGAACCGGGAGAACTGGAACTGGAA
TGTTCGTCTGAAAGACGCCTTCTCCAAAGGAGGTCAGACCGCACCGACCT
GTGCAGCCTGCCACATGGAATACGAAGGGGAATATACCCATAACATCACC
CGTAAGACCCGCTGGGCAAACTACCCGTTTGTTCCGGGGATTGCAGAAAA
CATCACCAGCGACTGGTCAGAAGCTCGTCTGGATTCCTGGGTTGTGACCT
GTACCCAATGTCACTCGGAACGGTTTGCCCGCTCCTACCTGGATCTCATG
GACAAAGGTACCCTGGAAGGGTTGGCTAAATACCAGGAAGCCAATGCCAT
TGTTCACAAAATGTATGAAGACGGCACCCTGACTGGTCAAAAAACCAATC
GTCCGAATCCACCGGCGCCAGAGAAACCGGGTTTTGGTATCTTCACCCAA
CTGTTCTGGTCCAAGGGTAACAACCCGGCCTCACTTGAACTGAAAGTGCT
GGAAATGGCAGAAAACAACCTGGCCAAAATGCACGTAGGACTGGCACACG
TTAATCCAGGTGGCTGGACATATACCGAAGGTTGGGGCCCGATGAACCGT
GCCTATGTTGAAATCCAGGATGAATACACCAAGATGCAGGAAATGACAGC
TCTGCAAGCGCGTGTTAACAAACTGGAAGGTAAAAAAACCAGCCTGCTTG
ACCTCAAGGGAGCGGGAGAAAAGATCTCGCTGGGAGGACTGGGAGGTGGC
ATGTTGCTGGCGGGAGCGATTGCTCTGATTGGCTGGCGTAAACGTAAGCA AACGCAAGCTTGA
SEQ ID c554 MKIIIACGLVAAALFTLTSGQSLAADAPFEGRKKCSSCHKPQAQSWKHTA NO:
24 cycA1 HAKAMESLKPNVKVEAKQKAKLDPTKDYTQDKDCVGCHVDGFGQKGGYTI (235
(D23_1c25 DSPKPMLTGVGCESCHGPGRKYRGDHRKAGQAFEKSGKKAPRKTLASKGQ aa)
27) DFNFEERCSACHLNYEGSPWKGAKPPYTPYTPEVDPKYTFKFDEMVKDVK protein
AMHEHYKLDGVFDGEPKFKFHDEFQANAKTAKKGK SEQ ID c554
ATGAAAATAATAATAGCCTGCGGACTGGTTGCTGCAGCCCTGTTCACCCT NO: 25 cycA1
GACAAGTGGGCAGAGTCTGGCAGCGGATGCTCCGTTTGAAGGTCGGAAAA (708 (D23_1c25
AGTGCAGTTCCTGTCACAAACCACAAGCCCAGTCGTGGAAACATACTGCC nt) 27) DNA
CACGCCAAGGCGATGGAATCGCTCAAGCCCAATGTCAAAGTGGAAGCCAA
ACAAAAAGCCAAACTGGATCCTACCAAGGACTACACCCAGGACAAAGACT
GCGTAGGTTGCCACGTGGATGGATTTGGCCAGAAAGGCGGCTACACGATA
GACTCCCCCAAACCCATGCTGACTGGCGTAGGCTGTGAATCCTGCCACGG
GCCTGGACGTAAATACCGGGGAGATCACCGCAAGGCCGGGCAAGCATTTG
AGAAATCGGGCAAAAAAGCGCCGCGCAAGACCCTGGCAAGCAAGGGGCAA
GACTTTAATTTTGAAGAACGTTGCAGCGCCTGCCATCTGAACTATGAAGG
GTCACCCTGGAAAGGAGCAAAACCTCCCTATACCCCGTATACACCGGAAG
TGGATCCGAAATACACCTTCAAGTTTGACGAGATGGTAAAAGACGTCAAA
GCCATGCACGAGCATTACAAACTGGATGGCGTATTTGACGGAGAGCCTAA
ATTCAAGTTCCATGACGAATTCCAGGCCAACGCTAAAACTGCCAAAAAAG GAAAATAG SEQ ID
cycA2 MKIIIACGLVAAALFTLTSGQSLAADAPFEGRKKCSSCHKPQAQSWKHTA NO: 26
(D23_1c19 HAKAMESLKPNVKVEAKQKAKLDPTKDYTQDKDCVGCHVDGFGQKGGYTI (235
24) DSPKPMLTGVGCESCHGPGRKYRGDHRKAGQAFEKSGKKAPRKTLASKGQ aa) protein
DFNFEERCSACHLNYEGSPWKGAKPPYTPYTPEVDPKYTFKFDEMVKDVK
AMHEHYKLDGVFDGEPKFKFHDEFQANAKTAKKGK SEQ ID cycA2
ATGAAAATAATAATAGCCTGCGGACTGGTTGCTGCAGCCCTGTTCACCCT NO: 27 (D23_1c19
GACAAGTGGGCAGAGTCTGGCAGCGGATGCTCCGTTTGAAGGTCGGAAAA (708 24) DNA
AGTGCAGTTCCTGTCACAAACCACAAGCCCAGTCGTGGAAACATACTGCC nt)
CACGCCAAGGCGATGGAATCGCTCAAGCCCAATGTCAAAGTGGAAGCCAA
ACAAAAAGCCAAACTGGATCCTACCAAGGACTACACCCAGGACAAAGACT
GCGTAGGTTGCCACGTGGATGGATTTGGCCAGAAAGGCGGCTACACGATA
GACTCCCCCAAACCCATGCTGACTGGCGTAGGCTGTGAATCCTGCCACGG
GCCTGGACGTAAATACCGGGGAGATCACCGCAAGGCTGGGCAAGCATTTG
AGAAATCGGGCAAAAAAGCGCCGCGCAAGACCCTGGCAAGCAAGGGGCAA
GACTTTAATTTTGAAGAACGTTGCAGCGCCTGCCATCTGAACTATGAAGG
GTCACCCTGGAAAGGAGCAAAACCTCCCTATACCCCGTATACACCGGAAG
TGGATCCGAAATACACCTTCAAGTTTGACGAGATGGTAAAAGACGTCAAA
GCCATGCACGAGCATTACAAACTGGATGGCGTATTTGACGGAGAGCCTAA
ATTCAAGTTCCATGACGAATTCCAGGCCAACGCTAAAACTGCCAAAAAAG GAAAATAG SEQ ID
cycA3 MKIIIACGLVAAALFTLTSGQSLAADAPFEGRKKCSSCHKPQAQSWKHTA NO: 28
(D23_1c17 HAKAMESLKPNVKVEAKQKAKLDPTKDYTQDKDCVGCHVDGFGQKGGYTI (235
86) DSPKPMLTGVGCESCHGPGRKYRGDHRKAGQAFEKSGKKAPRKTLASKGQ aa) protein
DFNFEERCSACHLNYEGSPWKGAKPPYTPYTPEVDPKYTFKFDEMVKDVK
AMHEHYKLDGVFDGEPKFKFHDEFQANAKTAKKGK SEQ ID cycA3
ATGAAAATAATAATAGCCTGCGGACTGGTTGCTGCAGCCCTGTTCACCCT NO: 29 (D23_1c17
GACAAGTGGGCAGAGTCTGGCAGCGGATGCTCCGTTTGAAGGTCGGAAAA (708 86) DNA
AGTGCAGTTCCTGTCACAAACCACAAGCCCAGTCGTGGAAACATACTGCC nt)
CACGCCAAGGCGATGGAATCGCTCAAGCCCAATGTCAAAGTGGAAGCCAA
ACAAAAAGCCAAACTGGATCCTACCAAGGACTACACCCAGGACAAAGACT
GCGTAGGTTGCCACGTGGATGGATTTGGCCAGAAAGGCGGCTACACGATA
GACTCCCCCAAACCCATGCTGACTGGCGTAGGCTGTGAATCCTGCCACGG
GCCTGGACGTAAATACCGGGGAGATCACCGCAAGGCTGGGCAAGCATTTG
AGAAATCGGGCAAAAAAGCGCCGCGCAAGACCCTGGCAAGCAAGGGGCAA
GACTTTAATTTTGAAGAACGTTGCAGCGCCTGCCATCTGAACTATGAAGG
GTCACCCTGGAAAGGAGCAAAACCTCCCTATACCCCGTATACACCGGAAG
TGGATCCGAAATACACCTTCAAGTTTGACGAGATGGTAAAAGACGTCAAA
GCCATGCACGAGCATTACAAACTGGATGGCGTATTTGACGGAGAGCCTAA
ATTCAAGTTCCATGACGAATTCCAGGCCAACGCTAAAACTGCCAAAAAAG GAAAATAG SEQ ID
cM552 MTRLQKGSIGTLLTGALLGIALVAVVFGGEAALSTEEFCTSCHSMSYPQS NO: 30
cycB1 ELKESTHYGALGVNPTCKDCHIPQGIENFHLAVATHVVDGARELWLEMVN (239
(D23_1c19 DYSTLEKFNERRLEMAHDARMNLKKWDSITCRTCHVKPAPPGESAQAEHK aa)
23) KMETEGATCIDCHQNLVHEEAPMTDLNASLAAGKLVLKPEEGDGDDDDDV protein
DVDDEEEDEEVEVEVEETETADDSDSASSSNHDDDSDDE SEQ ID cM552
ATGACTAGACTGCAAAAAGGATCAATTGGTACTTTACTGACAGGAGCTCT NO: 31 cycB1
GCTGGGAATAGCATTGGTGGCTGTGGTTTTTGGTGGGGAAGCTGCGTTAT (720 (D23_1c19
CGACCGAAGAGTTTTGTACCAGCTGTCATTCCATGTCATACCCACAGAGT nt) 23) DNA
GAATTAAAAGAATCCACCCACTATGGTGCATTGGGGGTTAATCCGACTTG
TAAAGACTGTCATATTCCACAAGGGATAGAAAATTTCCACCTGGCAGTAG
CAACTCACGTGGTTGATGGTGCCAGAGAACTTTGGTTGGAGATGGTCAAT
GACTACTCCACCCTGGAGAAGTTCAACGAAAGAAGATTGGAAATGGCGCA
TGATGCCCGGATGAACCTCAAGAAATGGGACAGCATCACCTGCCGTACCT
GTCATGTAAAACCAGCTCCTCCGGGAGAAAGCGCCCAGGCGGAACATAAG
AAAATGGAAACGGAAGGAGCAACCTGCATAGACTGTCATCAGAATCTGGT
GCATGAAGAAGCGCCGATGACAGATTTGAATGCAAGTCTTGCTGCAGGCA
AGCTGGTATTAAAGCCAGAAGAGGGTGACGGTGACGATGACGATGACGTT
GACGTTGATGACGAGGAGGAGGATGAAGAAGTCGAGGTGGAAGTTGAAGA
AACTGAAACAGCTGACGACAGCGACTCCGCTTCCTCCAGCAACCATGATG
ACGATAGTGATGATGAGTAA SEQ ID cycB2
MTRLQKGSIGTLLTGALLGIALVAVVFGGEAALSTEEFCTSCHSMSYPQS NO: 32 (D23_1c25
ELKESTHYGALGVNPTCKDCHIPQGIENFHLAVATHVVDGARELWLEMVN (239 26)
DYSTLEKFNERRLEMAHDARMNLKKWDSITCRTCHVKPAPPGESAQAEHK aa) protein
KMETEGATCIDCHQNLVHEEAPMTDLNASLAAGKLVLKPEEGDDDDDDDV
DVDDEEEDEEVEVEVEETETADDSDSASSSNHDDDSDDE SEQ ID cycB2
ATGACTAGACTGCAAAAAGGATCAATTGGCACTTTACTGACAGGAGCTCT NO: 33 (D23_1c25
GCTGGGAATAGCATTGGTGGCTGTGGTTTTTGGTGGGGAAGCTGCGTTAT (720 26) DNA
CGACCGAAGAGTTTTGTACCAGCTGTCATTCCATGTCATACCCACAGAGT nt)
GAATTAAAAGAATCCACCCACTATGGTGCATTGGGGGTTAATCCGACTTG
TAAAGACTGTCATATTCCACAAGGGATAGAAAATTTCCACCTGGCAGTAG
CAACTCACGTGGTTGATGGTGCCAGAGAACTTTGGTTGGAGATGGTCAAT
GACTACTCCACCCTGGAGAAGTTCAACGAAAGAAGATTGGAAATGGCGCA
TGATGCCCGGATGAACCTCAAGAAATGGGACAGCATCACCTGCCGTACCT
GTCATGTAAAACCAGCTCCTCCGGGAGAAAGCGCCCAGGCGGAACATAAG
AAAATGGAAACGGAAGGAGCAACCTGCATAGACTGTCATCAGAATCTGGT
GCATGAAGAAGCGCCGATGACAGATTTGAATGCAAGTCTTGCTGCAGGCA
AGCTGGTATTAAAGCCAGAAGAGGGTGACGATGACGATGACGATGACGTT
GACGTTGATGACGAGGAGGAGGATGAAGAAGTCGAGGTGGAAGTTGAAGA
AACTGAAACAGCTGACGACAGCGACTCCGCTTCCTCCAGCAACCATGATG
ACGATAGTGATGATGAGTAA
INCORPORATION BY REFERENCE
[0764] All publications and patents mentioned herein are hereby
incorporated by reference in their entirety as if each individual
publication or patent was specifically and individually indicated
to be incorporated by reference.
[0765] While specific embodiments of the subject invention have
been discussed, the above specification is illustrative and not
restrictive. Many variations of the invention will become apparent
to those skilled in the art upon review of this specification and
the claims below. The full scope of the invention should be
determined by reference to the claims, along with their full scope
of equivalents, and the specification, along with such
variations.
[0766] Certain embodiments are within the following claims.
Sequence CWU 0 SQTB SEQUENCE LISTING The patent application
contains a lengthy "Sequence Listing" section. A copy of the
"Sequence Listing" is available in electronic form from the USPTO
web site
(http://seqdata.uspto.gov/?pageRequest=docDetail&DocID=US20170037363A1).
An electronic copy of the "Sequence Listing" will also be available
from the USPTO upon request and payment of the fee set forth in 37
CFR 1.19(b)(3).
0 SQTB SEQUENCE LISTING The patent application contains a lengthy
"Sequence Listing" section. A copy of the "Sequence Listing" is
available in electronic form from the USPTO web site
(http://seqdata.uspto.gov/?pageRequest=docDetail&DocID=US20170037363A1).
An electronic copy of the "Sequence Listing" will also be available
from the USPTO upon request and payment of the fee set forth in 37
CFR 1.19(b)(3).
* * * * *
References