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Mycobacterium bovis BCG genes involved in the biosynthesis of cyclopropyl keto‐ and hydroxy‐mycolic acids
Author(s) -
Dubnau Eugenie,
Lanéelle MarieAntoinette,
Soares Sonia,
Bénichou Anne,
Vaz Tania,
Promé Danielle,
Promé JeanClaude,
Daffé Mamadou,
Quémard Annai¨k
Publication year - 1997
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1046/j.1365-2958.1997.2301589.x
Subject(s) - mycolic acid , mycobacterium smegmatis , mycobacterium bovis , mycobacterium tuberculosis , mycobacterium , biochemistry , microbiology and biotechnology , biosynthesis , biology , gene , chemistry , tuberculosis , bacteria , genetics , medicine , pathology
The resurgence of tuberculosis and the emergence of multidrug‐resistant mycobacteria necessitate the development of new antituberculosis drugs. The biosynthesis of mycolic acids, essential elements of the mycobacterial envelope, is a good target for chemotherapy. Species of the Mycobacterium tuberculosis complex synthesize oxygenated mycolic acids with keto and methoxy functions. In contrast, the fast‐growing Mycobacterium smegmatis synthesizes oxygenated mycolic acids with an epoxy function. We describe the isolation and sequencing of a cluster of four genes from Mycobacterium bovis bacillus Calmette–Guérin (BCG), coding for methyl transferases, and which, when transferred into M. smegmatis ,allow the synthesis of ketomycolic acid, in addition to an as yet undescribed mycolic acid, hydroxymycolic acid. These oxygenated mycolic acids, unlike the regular mycolic acids of M. smegmatis , and similar to the mycolic acids of M. bovis , are highly cyclopropanated. Furthermore, there is a perfect match between the structures of the keto‐ and the hydroxy‐mycolic acids. We propose a biosynthetic model in which there is a direct relationship between these two types of mycolic acid.