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Carbon monoxide dehydrogenase:A novel target for the development of
new anti-tubercular drugs
Young Min KimDepartment of Biology, Yonsei University
Molecular Microbiology Laboratory, Yonsei University
From Basic to Application
1979: Entered to the CO world (George Hegeman’s Lab., Indiana University)1982: Moved to Yonsei University1985: Isolation of a new CO-oxidizing bacteria2002: Reclassification of the CO-oxidizing isolate2003: Mycobacteria and CO2007: Mycobacterial CO dehydrogenase possesses NO dehydrogenase activity and enhances the survival of Mycobacterium tuberculosis in macrophages
Molecular Microbiology Laboratory, Yonsei University
Studies on the oxidation of CO by bacteria
CO
Molecular Microbiology Laboratory, Yonsei University
- An air pollutant
- A color- and odorless toxic gas : high affinity to metal-containing enzymes (e.g. hemoglobin, a-type cytochromes)
- Also acts as a neurotransmitter : the one produced endogenously during heme degradation
Production and sources - 12 - 14 x 108 tons per year - Major source : incomplete oxidation of fossil fuels
* Constant concentration in atmosphere : 0.03 - 0.9 ppm (50 - 100 ppm in urban district)
Sinks - Major sink (2/3) : Oxidation by hydroxyl radical in the upper atmosphere (troposphere) - Biological oxidation, especially microbial oxidation, plays a major role in the lower atmosphere (soil and water)
Molecular Microbiology Laboratory, Yonsei University
Carboxydobacteria
- A group of aerobic bacteria which are able to grow at the expense of carbon monoxide as the sole source of carbon and energy
- Facultatively chemolithoautotrophs
Molecular Microbiology Laboratory, Yonsei University
Bases of CO utilization
CO dehydrogenase
CO-insensitive electron transport system
Calvin cycle * Mycobacterium tuberculosis: reductive TCA cycle (?)
Molecular Microbiology Laboratory, Yonsei University
CO dehydrogenases
Aerobic bacteria - carboxydobacteria - metals: Mo, Cu, Fe
Anaerobic bacteria - acetogenic bacteria, methanogenic bacteria, phototrophic bacteria, sulfate reducers - metals: Ni, Fe
Molecular Microbiology Laboratory, Yonsei University
CO dehydrogenases in carboxydobacteria
300-380 kD
3 nonidentical subunits (L2M2S2)
Molybdopterin cytosine dinucleotide:[2Fe-2S]:FAD (2:4:2)
Inducible by CO * Mycobacterium sp. strain JC1: constitutive & CO-inducible
Molecular Microbiology Laboratory, Yonsei University
FAD
FeS II
FeS I
MCD-Mo
O. Meyer’s group
O. carboxidovorans
Molecular Microbiology Laboratory, Yonsei University
CO + H2O CO-DH(MCD-HCOO- + H+/[Fe-S]/FAD) CO2
CO-DH(MCD/[Fe-S]/FADH2) CO-DH(MCD/[Fe-S]/FAD) 2H+ + 2e-
Oxidation of CO by CO dehydrogenase
Molecular Microbiology Laboratory, Yonsei University
CO + H2O CO2 + 2H+ + 2e-
Organic materials
NADH UQ/Cyt. b Cyt. c Cyt. a O2
CO UQ/Cyt. b Cyt. o O2
NADH
Electron transport system
Molecular Microbiology Laboratory, Yonsei University
CO2 fixation in carboxydobacteria
Molecular Microbiology Laboratory, Yonsei University
Calvin cycle
Reductive TCA cycle (?)
Hydroxypropionate pathway
Acetyl-CoA pathway
CO + H2O CO-DH(MCD-HCOO- + H+/[Fe-S]/FAD) CO2
CO-DH(MCD/[Fe-S]/FADH2) CO-DH(MCD/[Fe-S]/FAD) 2H+ + 2e-
Oxidation of CO by CO dehydrogenase
Molecular Microbiology Laboratory, Yonsei University
CO + H2O CO2 + 2H+ + 2e-
Cellular
materials
Energy
Mycobacteria and CO
Molecular Microbiology Laboratory, Yonsei University
Reclassification of CO-oxidizing isolate
Molecular Microbiology Laboratory, Yonsei University
Acinetobacter sp. strain JC1 (1985)
Mycobacterium sp. strain JC1 (2002)
Mycobacterial carboxydobacteria
++
+ + + +
M. phlei
M. flavescens
+ + +M. peregrinum
+ + +M. neoaurum
+ + +M. Smegmatis MC2
+ + +M. gastri
+ + +M. vaccae+ + +
- + +M. tuberculosis H37Ra
+ + +Mycobacterium sp. strain JC1
M. parafortuitum
Growth on CO
CO-DHactivity
RubisCOactivityBacteria
Molecular Microbiology Laboratory, Yonsei University
Park et al., J. Bacteriol. 185:142-147 (2003)
Activity staining and Immunoblotting of CO-DHs in mycobacteria
1 2 3 4 5 6 7 8 9 10
A
B
Molecular Microbiology Laboratory, Yonsei University
Identity of amino acid sequence of Mycobacterium sp. strain JC1 CO-DH to those of CO-DHs in other bacteria
Large Medium SmallBacteria
O. carboxidovorans
P. thermocarboxydovorans
H. pseudoflava
M. tuberculosis
55.7 38.2 57.7
57.7 36.9 57.4
57.8 40.4 57.0
87.7 71.2 81.7
Amino acid identity (%)
Molecular Microbiology Laboratory, Yonsei University
* No immunological relationship between CO-DHs in mycobacteria and Gram-negative bacteria
moaE cutR cutB1 cutC1 cutA1 orf7 orf8 orf9 orf10 orf11 orf12 orf13modC cutB2 cutC2 cutA2 orf17 orf18 orf19 orf20 orf21
Mycobacterim sp. strain JC1
M. tuberculosis H37Rv
0376c 0375c 0374c 0373c 0372c 0370c0371c 0369c rv0377 0368c
0383c 0382c 0381c 0380c 0379c 0377c0378c 0376cmb0384 0375c
M. bovis0414c 0413c 0412c 0411c 0410c 0408c0409c 0407cbcg0415 0406c
M. bovis BCG
M. marinum0654 0655 0656 0657 0658 06600659 0661mmar0653 0662
M. smegmatis
0743 0744 0745 0746 0747 07490748msmeg0742 0750
cutM cutS cutL
H. pseudoflava
orf1
cutB cutC cutA orf4
O. carboxidovorans
P. thermocarboxydovorans
0477 0478 0479 0480 0481 04830482mjls0476 0484
Mycobacterium sp. JLS0499 0500 0501 0502 0503 05050504mkms0498 0506
Mycobacterium sp. KMS0488 0489 0490 0491 0492 04940493mmcs0487 0495
Mycobacterium sp. MCS
coxC coxM coxS coxL coxD coxE coxGcoxB coxHcoxF coxKcoxI
trd_A0566 0565 0564 0563
T. roseum coxC coxM coxS coxL coxD coxE coxF coxG
R. jostii 0523205231rha1_ro05229 05230 05233 0523505234 05236
1 kb
Molecular Microbiology Laboratory, Yonsei University
CO-DH genes and conserved genes up- and downstream of the CO-DH genes in mycobacteria
Park et al., Microbiology 156:999-1008 (2010)
What is the physiological role ofCO dehydrogenase in
pathogenic mycobacteria?
Molecular Microbiology Laboratory, Yonsei University
Molecular Microbiology Laboratory, Yonsei University
MW: 28 MW: 30
NO
Molecular Microbiology Laboratory, Yonsei University
- An air pollutant
- An important signaling molecule in human body- Beneficial and detrimental
- Kills bacteria in macrophages
CO-DH and NO-DH activities in mycobacterial and a Gram-negative carboxydobacteriaa
Molecular Microbiology Laboratory, Yonsei University
Park et al., BBRC 362:449-453 (2007)
a Activity was determined with cell-free extracts prepared from cells grown at 37oC in SMB-CO.b Nanomoles of INT reduced per milligram of protein per minute.
NO source: sodium nitroprusside (SNP)
BacteriaSpecific activityb
SourceCO-DH NO-DH
Mycobacterium sp. strain JC1 DSM 3803 M. tuberculosis H37Ra ATCC 35835M. vaccae ATCC 15483O. carboxidovorans OM5 DSM 1227
6.09.9
17.518.1
1.52.03.10.0
1 21 2
Lane 1: Stained for CO-DH (CO) Lane 2: Stained for NO-DH (SNP)
CO-DH and NO-DH stained by activity
Molecular Microbiology Laboratory, Yonsei University
Purified CO-DH of Mycobacterium sp. strain JC1 - CO-DH activity : 139.3 nmol of INT reduced/mg protein/min - NO-DH activity : 32.6 nmol of INT reduced/mg protein/min
Purified CO-DH possesses NO-DH activity
CO-DH activity : 150 mM methanol NO-DH activity : 75 mM methanol
CO-DH and NO-DH activities were inhibited by methanol
Molecular Microbiology Laboratory, Yonsei University
Molecular Microbiology Laboratory, Yonsei University
NO + H2O NO2 + 2H+ + 2e-
Oxidation of NO by NO-DH activity of CO-DH
CO + H2O CO2 + 2H+ + 2e-
CO-DH and NO-DH activities in cells incubated in the presence and absence of SNPa
a Cells were grown in SMB-CO in the presence (+SNP) and absence (-SNP) of 5 mM SNP. Activity was determined with cell-free extracts prepared from cells harvested at the indicated time intervals after inoculation of the CO-grown cells into the appropriate medium.b Nanomoles of INT reduced per milligram of protein per minute.
Molecular Microbiology Laboratory, Yonsei University
Bacteria
Specific activityb
CO-DH NO-DH
Mycobacterium sp. strain JC1
O. carboxidovorans OM5
02040
5.7 8.5 0.0
17.6 7.6 7.8
Time after inoculation
(min)
1.51.41.5
0.00.00.0
1.52.10.0
0.00.00.0
-SNP +SNP –SNP +SNP
5.75.76.0
17.617.014.5
02040
Effect of SNP on the expression of CO-DH
Immunoblotting of CO-DH
Mycobacterium sp. strain JC1 SMB-glucose + SNP
0 20 40(min)
Panel A: Mycobacterium sp. JC1, CO, stained with CBBPanel B: Mycobacterium sp. JC1, CO, stained by activityPanel C: Mycobacterium sp. JC1, glucose, stained by activityPanel D: O. carboxidovorans OM5, CO, stained by activity Cells were harvested at the time of inoculation (lane 1) and at 20 min (lane 2) and 40 min (lane 3) after inoculation
-SNP +SNP
1 2 3 1 2 3
A
B
C
D
Molecular Microbiology Laboratory, Yonsei University
Tuberculosis
Molecular Microbiology Laboratory, Yonsei University
- A common and often deadly disease caused in human mainly by Mycobacterium tuberculosis
- Systemic but usually attacks lung
• Infects over a third of the world’s population (~2 billions)
- one in 10 asymptomatic latent infections progresses to active TB (8~9 millions per year)
• Accounts for 2 million death annually (one every 15-20 seconds)
• Infects a fourth of AIDS patients - accounts for a third of AIDS patient’s death
Molecular Microbiology Laboratory, Yonsei University
M. tuberculosis
Molecular Microbiology Laboratory, Yonsei University
RNSROS
RNS
Strategies of mycobacteria to survive inside host macrophages
1. Prevention of phagosome-lysosome fusion
2. Inactivation of toxic reactive oxygen species by KatG etc.
3. Inactivation of toxic reactive nitrogen species by; - NO dioxygenase activity of Hmp and trHbN - Peroxinitritase activity of KatG and alkylhydroperoxide reductase AhpC
Molecular Microbiology Laboratory, Yonsei University
ROS
RNS
Strategies of mycobacteria to survive inside host macrophages
1. Prevention of phagosome-lysosome fusion
2. Inactivation of toxic reactive oxygen species by KatG etc.
3. Inactivation of toxic reactive nitrogen species by; - NO dioxygenase activity of Hmp and trHbN - Peroxinitritase activity of KatG and alkylhydroperoxide reductase AhpC - NO-DH activity of CO-DH (?)
Molecular Microbiology Laboratory, Yonsei University
ROS
Effect of CO-DH on the survival of E. coli under NO stress
Molecular Microbiology Laboratory, Yonsei University
E. coli DH5α, 5 mM SNP, 50 mM Tris-HCl (pH 7.5), RT 50 g of Mycobacterium sp. JC1 purified CO-DH
Effect of NO on the survival of Mycobacterium sp. JC1 cutR- mutant under NO stress
Mycobacterium sp. strain JC1 wild type and cutR- mutant cells, 5 mM SNP, RT
Molecular Microbiology Laboratory, Yonsei University
cutR cutB cutC cutA212 2555 2984 7669
2 3244 3564 3906 4686 6916 7152
2 3167 3487 3829 4609 6839 7075
2464 2907 7592
BamHI
EcoRI
(base)
BamHI
EcoRI
(base)
Copy 1
Copy 2
cutR cutB cutC cutA212 2555 2984 7669
2 3244 3564 3906 4686 6916 7152
2 3167 3487 3829 4609 6839 7075
2464 2907 7592
BamHI
EcoRI
(base)
BamHI
EcoRI
(base)
Copy 1
Copy 2
Effect of NO on the survival of Mycobacterium sp. strain JC1 cutA- mutant under NO stress
Molecular Microbiology Laboratory, Yonsei University
cutR cutB cutC cutA212 2555 2984 7669
2 3244 3564 3906 4686 6916 7152
2 3167 3487 3829 4609 6839 7075
2464 2907 7592
BamHI
EcoRI
(base)
BamHI
EcoRI
(base)
Copy 1
Copy 2
cutR cutB cutC cutA212 2555 2984 7669
2 3244 3564 3906 4686 6916 7152
2 3167 3487 3829 4609 6839 7075
2464 2907 7592
BamHI
EcoRI
(base)
BamHI
EcoRI
(base)
Copy 1
Copy 2
Effect of NO on the survival of M. smegmatis cutA- mutant under NO stress
Molecular Microbiology Laboratory, Yonsei University
cutR orf2cutC cutAcutB orf4 orf5 orf6orf1cutR orf2cutC cutAcutB orf4 orf5 orf6orf1
Survival of M. tuberculosis H37Rv in macrophage
Molecular Microbiology Laboratory, Yonsei University
Wild type-1Wild type-2CO-DH mutant#1-1CO-DH mutant#1-2CO-DH mutant#2-1CO-DH mutant#2-1
0372c0374c 0373c0375c 0371c 0370c0376c0377 0369c 0368c0372c0374c 0373c0375c 0371c 0370c0376c0377 0369c 0368c0372c0374c 0373c0375c 0371c 0370c0376c0377 0369c 0368c0372c0374c 0373c0375c 0371c 0370c0376c0377 0369c 0368c
Strategies of mycobacteria to survive inside host macrophages
1. Prevention of phagosome-lysosome fusion
2. Inactivation of toxic reactive oxygen species by KatG etc.
3. Inactivation of toxic reactive nitrogen species by; - NO dioxygenase activity of Hmp and trHbN - Peroxinitritase activity of KatG and alkylhydroperoxide reductase AhpC
- NO-DH activity of CO-DH
Molecular Microbiology Laboratory, Yonsei University
Molecular Microbiology Laboratory, Yonsei University
Possible role of CO-DH in pathogenic mycobacteria
NOCO
CO-DH
Known anti-tuberculosis drugs and genes inducing resistance to the drugs
Anti-tuberculosis drugs Action mechanism
Genes involved in the resistanceMutation rate (%)Genes Products Roles
IsoniazidInhibition of mycolic acid biosynthesisInhibition of DNA, lipids, carbohydrates, and NAD metabolism
katG Catalase- peroxidase Prodrug conversion 20-80
inhA Enoyl ACP reductase Drug target 15-43
ndh NADH dehydrogenase II INH activity modulator 10
ahpC Alkyl hydroperoxidase Marker of resistance 10-15
Rifampin Inhibition of transcription rpoB RNA polymerase Drug target 96
PyrazinamideAcidification of cytoplasmLoss of membrane energy
pncA Nicotinamidase/pyrazinamidase Prodrug conversion 72-97
5-Chloro-pyrazinamide Inhibition of FASI fasI FASI Drug target NA
EthambutolInhibition of arabinogalactan biosynthesis
embCAB Arabinosyltransferases Drug target 47-65
Streptomycin Inhibition of protein synthesisrpsL S12 ribosomal protein Drug target 52-59
rrs 16S rRNA Drug target 8-21
Amikacin/kanamycin Inhibition of protein synthesis rrs 16S rRNA Drug target 76
Streptomycin Inhibition of protein synthesisrpsL S12 ribosomal protein Drug target 52-59
rrs 16S rRNA Drug target 8-21
Ethionamide Inhibition of mycolic acid biosynthesisetaA/ethA Flavin monooxygenase Prodrug conversion 37
inhA Enoyl ACP reductase Drug target 56
Molecular Microbiology Laboratory, Yonsei University
Known anti-tuberculosis drugs and genes inducing resistance to the drugs
Anti-tuberculosis drugs Action mechanism
Genes involved in the resistanceMutation rate (%)Genes Products Roles
IsoniazidInhibition of mycolic acid biosynthesisInhibition of DNA, lipids, carbohydrates, and NAD metabolism
katG Catalase- peroxidase Prodrug conversion 20-80
inhA Enoyl ACP reductase Drug target 15-43
ndh NADH dehydrogenase II INH activity modulator 10
ahpC Alkyl hydroperoxidase Marker of resistance 10-15
Rifampin Inhibition of transcription rpoB RNA polymerase Drug target 96
PyrazinamideAcidification of cytoplasmLoss of membrane energy
pncA Nicotinamidase/pyrazinamidase Prodrug conversion 72-97
5-Chloro-pyrazinamide Inhibition of FASI fasI FASI Drug target NA
EthambutolInhibition of arabinogalactan biosynthesis
embCAB Arabinosyltransferases Drug target 47-65
Streptomycin Inhibition of protein synthesisrpsL S12 ribosomal protein Drug target 52-59
rrs 16S rRNA Drug target 8-21
Amikacin/kanamycin Inhibition of protein synthesis rrs 16S rRNA Drug target 76
Streptomycin Inhibition of protein synthesisrpsL S12 ribosomal protein Drug target 52-59
rrs 16S rRNA Drug target 8-21
Ethionamide Inhibition of mycolic acid biosynthesisetaA/ethA Flavin monooxygenase Prodrug conversion 37
inhA Enoyl ACP reductase Drug target 56
Molecular Microbiology Laboratory, Yonsei University
Multi-drug resist
ant TB
Extensively drug-resistant TB
No new anti-TB drug has beenintroduced in the last four decades
→ needs novel targets with less mutation rate
CO-oxidizing system as a novel target for TB drug screening
1. CO dehydrogenase : screening for natural and synthetic compounds
2. Proteins involved in the expression of CO
dehydrogenase
Molecular Microbiology Laboratory, Yonsei University
0372c0374c 0373c0375c 0371c 0370c0376c0377 0369c 0368c0372c0374c 0373c0375c 0371c 0370c0376c0377 0369c 0368c
0372c0374c 0373c0375c 0371c 0370c0376c0377 0369c 0368c0372c0374c 0373c0375c 0371c 0370c0376c0377 0369c 0368c
Functional analysis of genes (possibly) involved in the oxidation of CO in mycobactera
Molecular Microbiology Laboratory, Yonsei University
Mycobacterium smegmatis
Mycobacterium tuberculosis
Mycobacterium sp. strain JC1cutR orf2cutC cutAcutB orf3 orf4 orf5
orf2cutC cutAcutB orf3 orf4orf1 orf6
Copy I
Copy IIorf5
Genes Mutant Function Structure
cutR orf1cutBCAorf2orf3 orf4 orf5 orf6
regulation unknownCO-DH unknown Const. exp. (?) unknown unknownregulation
OXOOXOXO
OOXXOXXX
cutR orf2cutC cutAcutB orf4 orf5 orf6orf1
Ribbon diagram of CutR in Mycobacterium sp. strain JC1
Molecular Microbiology Laboratory, Yonsei University
cutR orf2cutC cutAcutB orf3 orf4 orf5
orf2cutC cutAcutB orf3 orf4orf1 orf6orf5
Ribbon diagram of Orf1 in M. smegmatis
Molecular Microbiology Laboratory, Yonsei University
0372c0374c 0373c0375c 0371c 0370c0376c0377 0369c 0368c0372c0374c 0373c0375c 0371c 0370c0376c0377 0369c 0368c
Ribbon diagram of Orf3 in Mycobacterium sp. strain JC1
Molecular Microbiology Laboratory, Yonsei University
cutR orf2cutC cutAcutB orf3 orf4 orf5
orf2cutC cutAcutB orf3 orf4orf1 orf6orf5
Dr. Jin Won Cho (Yonsei Univ.)
Molecular Microbiology Laboratory, Yonsei University
Dr. Sae Woong Park (Weill Cornell Medical College)
Dr. Taeksun Song(KNIH)
Dr. Beom Sik Kang(Kyungpook Natl. Univ.)
Seo Young Kim
Hyuk Park
Seung Mi Kim
Jae Ho Lee
Seung Jung Han
Thank youfor
your attention
Carboxydobacteria
- A group of aerobic bacteria which are able to grow at the expense of carbon monoxide as the sole source of carbon and energy
- Facultatively chemolithotrophic bacteria
- Gram(-) carboxydobacteria Mycobacterial carboxydobacteria Gram(+) carboxydobacteria other than mycobacteria
Molecular Microbiology Laboratory, Yonsei University
Carboxydobacteria
A group of aerobic bacteria which are able to grow at the expense of carbon monoxide as the sole source of carbon and energy
Gram negative - Pseudomonas carboxydohydrogena - Hydrogenophaga pseudoflava Oligotropha carboxidovorans
Gram positive Mycobacterium sp. strain JC1 ( Acinetobacter sp. strain JC1)
Molecular Microbiology Laboratory, Yonsei University
2002
moaE cutR cutB1 cutC1 cutA1 orf7 orf8 orf9 orf10 orf11 orf12 orf13modC cutB2 cutC2 cutA2 orf17 orf18 orf19 orf20 orf21
Mycobacterim sp. strain JC1
M. tuberculosis H37Rv
0376c 0375c 0374c 0373c 0372c 0370c0371c 0369c rv0377 0368c
0383c 0382c 0381c 0380c 0379c 0377c0378c 0376cmb0384 0375c
M. bovis0414c 0413c 0412c 0411c 0410c 0408c0409c 0407cbcg0415 0406c
M. bovis BCG
M. marinum0654 0655 0656 0657 0658 06600659 0661mmar0653 0662
M. smegmatis
0743 0744 0745 0746 0747 07490748msmeg0742 0750
cutM cutS cutL
H. pseudoflava
orf1
cutB cutC cutA orf4
O. carboxidovorans
P. thermocarboxydovorans
0477 0478 0479 0480 0481 04830482mjls0476 0484
Mycobacterium sp. JLS0499 0500 0501 0502 0503 05050504mkms0498 0506
Mycobacterium sp. KMS0488 0489 0490 0491 0492 04940493mmcs0487 0495
Mycobacterium sp. MCScoxC coxM coxS coxL coxD coxE coxGcoxB coxHcoxF coxKcoxI
trd_A0566 0565 0564 0563
T. roseum coxC coxM coxS coxL coxD coxE coxF
R. pomeroyi
coxG
sace 0534 0537 0538 05390535 0536
S. erythraea
bxe_C0029 0030 0031 0032 0033 00350034rcoM
B. xenovorans chromosome 3
B. xenovorans chromosome 1
0036
bxe_A4360 4356 435443574358 43554359
04976 04975rha1_ro04979 0497704978
R. jostii 0523205231rha1_ro05229 05230 05233 0523505234 05236
Gra
m
(-)G
ram
(+
)m
ycob
acte
ria
1 kb
ABG06612
ABL89718
ABN96292
ABK70147
JC1
ACC39118
ABL02876
CAA17379
CAD93243
CAL70396
ABG97013
ACM06436
AAV95654
CAA57829
AAD00363
CAA54902
ABE30822
ABE35958
ABG96757
CAL99883100
100
99
100
98
100
63
74
100
100
91
100
100 83
81 43
69
0.10.1 substitutions per site
Gro
up
II
Gro
up
III
Gro
up
I
Thermomicrobium roseum Trd_A0564 (ACM06436)
Hydrogenophaga pseudoflava CutL (AAD00363)
Pseudomonas thermocarboxydovorans CutA (CAA54902)
Ruegeria pomeroyi CoxL (AAV95654)
Mycobacterium sp. strain JC1 CutA (FJ896490)
Oligotropha carboxidovorans CoxL (CAA57829)
Burkholderia xenovorans CoxL2 (ABE30822)
Burkholderia xenovorans CoxL (ABE35958)
Rhodococcus jostii RHA1_ro04976 (ABG96757)
Saccharopolyspora erythraea SACE_0537 (CAL99883)
Mycobacterium smegmatis MSMEG_0746 (ABK70147)
Mycobacterium sp. MCS Mmcs_0491 (ABG06612)
Mycobacterium sp. KMS Mkms_0502 (ABL89718)
Mycobacterium sp. JLS Mjls_0480 (ABN96292)
Mycobacterium marinum CoxL (ACC39118)
Mycobacterium ulcerans CoxL (ABL02876)
Mycobacterium tuberculosis Rv0373c (CAA17379)
Mycobacterium bovis Mb0380c (CAD93243)
Mycobacterium bovis BCG BCG_0411c (CAL70396)
Rhodococcus jostii RHA1_ro05232 (ABG97013)
CO-DH large subunit
Molecular Microbiology Laboratory, Yonsei University
Oxidation of CO by Anaerobic CO dehydrogenase
Molecular Microbiology Laboratory, Yonsei University