The preponderance of P450s in the Mycobacterium tuberculosis genome

Kirsty J. McLean; Daniel Clift; D. Geraint Lewis; Muna Sabri; Philip R. Balding; Michael J. Sutcliffe; David Leys; Andrew W. Munro

doi:10.1016/j.tim.2006.03.002

The preponderance of P450s in the Mycobacterium tuberculosis genome

Kirsty J. McLean, Daniel Clift, D. Geraint Lewis, Muna Sabri, Philip R. Balding, Michael J. Sutcliffe, David Leys, Andrew W. Munro

Research output: Contribution to journal › Review article › peer-review

64 Citations (Scopus)

Abstract

The genome of Mycobacterium tuberculosis (Mtb) encodes 20 different cytochrome P450 enzymes (P450s). P450s are mono-oxygenases, which are historically considered to facilitate prokaryotic usage of unusual carbon sources. However, their preponderance in Mtb strongly indicates crucial physiological functions, as does the fact that polycyclic azoles (known P450 inhibitors) have potent anti-mycobacterial effects. Recent structural and enzyme characterization data reveal novel features for at least two Mtb P450s (CYP121 and CYP51). Genome analysis, knockout studies and structural comparisons signify important roles in cell biology and pathogenesis for various P450s and redox partner enzymes in Mtb. Elucidation of structure, function and metabolic roles will be essential in targeting the P450s as an 'Achilles heel' in this major human pathogen.

Original language	English
Pages (from-to)	220-228
Number of pages	9
Journal	Trends in Microbiology
Volume	14
Issue number	5
Early online date	3 Apr 2006
DOIs	https://doi.org/10.1016/j.tim.2006.03.002
Publication status	Published - 1 May 2006
Externally published	Yes

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title = "The preponderance of P450s in the Mycobacterium tuberculosis genome",

abstract = "The genome of Mycobacterium tuberculosis (Mtb) encodes 20 different cytochrome P450 enzymes (P450s). P450s are mono-oxygenases, which are historically considered to facilitate prokaryotic usage of unusual carbon sources. However, their preponderance in Mtb strongly indicates crucial physiological functions, as does the fact that polycyclic azoles (known P450 inhibitors) have potent anti-mycobacterial effects. Recent structural and enzyme characterization data reveal novel features for at least two Mtb P450s (CYP121 and CYP51). Genome analysis, knockout studies and structural comparisons signify important roles in cell biology and pathogenesis for various P450s and redox partner enzymes in Mtb. Elucidation of structure, function and metabolic roles will be essential in targeting the P450s as an 'Achilles heel' in this major human pathogen.",

keywords = "Comamonas Testosteroni, Cytochrome P-450 Cyp121, Mycobaterium Tuberculosis",

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AU - McLean, Kirsty J.

AU - Clift, Daniel

AU - Lewis, D. Geraint

AU - Sabri, Muna

AU - Balding, Philip R.

AU - Sutcliffe, Michael J.

AU - Leys, David

AU - Munro, Andrew W.

PY - 2006/5/1

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N2 - The genome of Mycobacterium tuberculosis (Mtb) encodes 20 different cytochrome P450 enzymes (P450s). P450s are mono-oxygenases, which are historically considered to facilitate prokaryotic usage of unusual carbon sources. However, their preponderance in Mtb strongly indicates crucial physiological functions, as does the fact that polycyclic azoles (known P450 inhibitors) have potent anti-mycobacterial effects. Recent structural and enzyme characterization data reveal novel features for at least two Mtb P450s (CYP121 and CYP51). Genome analysis, knockout studies and structural comparisons signify important roles in cell biology and pathogenesis for various P450s and redox partner enzymes in Mtb. Elucidation of structure, function and metabolic roles will be essential in targeting the P450s as an 'Achilles heel' in this major human pathogen.

AB - The genome of Mycobacterium tuberculosis (Mtb) encodes 20 different cytochrome P450 enzymes (P450s). P450s are mono-oxygenases, which are historically considered to facilitate prokaryotic usage of unusual carbon sources. However, their preponderance in Mtb strongly indicates crucial physiological functions, as does the fact that polycyclic azoles (known P450 inhibitors) have potent anti-mycobacterial effects. Recent structural and enzyme characterization data reveal novel features for at least two Mtb P450s (CYP121 and CYP51). Genome analysis, knockout studies and structural comparisons signify important roles in cell biology and pathogenesis for various P450s and redox partner enzymes in Mtb. Elucidation of structure, function and metabolic roles will be essential in targeting the P450s as an 'Achilles heel' in this major human pathogen.

KW - Comamonas Testosteroni

KW - Cytochrome P-450 Cyp121

KW - Mycobaterium Tuberculosis

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JO - Trends in Microbiology

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The preponderance of P450s in the Mycobacterium tuberculosis genome

Abstract

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