Mycobacterium bovis BCG genes involved in the biosynthesis of cyclopropyl keto‐ and hydroxy‐mycolic acids

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 tubercu...

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Bibliographic Details
Published in:Molecular microbiology 1997-01, Vol.23 (2), p.313-322
Main Authors: Dubnau, Eugenie, Lanéelle, Marie‐Antoinette, Soares, Sonia, Bénichou, Anne, Vaz, Tania, Promé, Danielle, Promé, Jean‐Claude, Daffé, Mamadou, Quémard, Annai¨k
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Bacterial Proteins
Biochemistry
Biochemistry, Molecular Biology
Cloning, Molecular
Genes, Bacterial - physiology
Life Sciences
Methyltransferases - genetics
Methyltransferases - isolation & purification
Molecular Sequence Data
Mycobacterium bovis
Mycobacterium bovis - genetics
Mycobacterium bovis - metabolism
Mycobacterium smegmatis
Mycobacterium tuberculosis
Mycolic Acids - metabolism
Sequence Alignment
Sequence Analysis, DNA
Tuberculosis, Multidrug-Resistant
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Summary: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.
ISSN:0950-382X
1365-2958
DOI:10.1046/j.1365-2958.1997.2301589.x