Mycobacterium bovis BCG genes involved in the biosynthesis of cyclopropyl keto- and hydroxy-mycolic acids |
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Authors: | Eugenie Dubnau,Marie-Antoinette Lané elle,Sonia Soares,Anne Bé nichou,Tania Vaz,Danielle Promé ,Jean-Claude Promé ,Mamadou Daffé ,& Annai¨ k Qué mard |
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Affiliation: | Public Health Research Institute, 455 First Avenue, New York 10016, USA; Institut de Pharmacologie et de Biologie Structurale, CNRS, 118 route de Narbonne, 31062 Toulouse, France. |
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Abstract: | 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. |
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