STRUCTURE OF A HYDROXYMYCOLIC ACID POTENTIALLY INVOLVED IN THE SYNTHESIS OF OXYGENATED MYCOLIC ACIDS OF THE MYCOBACTERIUM-TUBERCULOSIS COMPLEX

Mycolic acids are believed to play a crucial role in the architecture of the mycobacterial envelope. However, very few steps of their biosyn thetic pathway have yet been elucidated. We previously isolated [Dubna u, E., Laneelle, M. A., Soares, S., Benichou, A., Vaz, T., Prome, D., Prome, J. C., Daffe, M. & Quemard, A. (1997) Mycobacterium bovis BCG g enes involved in the biosynthesis of cyclopropyl keto- and hydroxy-myc olic acids, Mol. Microbiol. 23, 313-322] a gene cluster from Mycobacte rium bovis BCG, cmnA-D, which confers upon hi, smegmatis the ability t o synthesize cyclopropanated ketomycolic acid, and a new type of mycol ic acid which is hydroxylated. A meticulous analysis of all the mycoli c-like fatty acids of hi. bovis BCG and M. tuberculosis showed that th ese organisms produce smell amounts of the hydroxymycolic acid. The st ructure of this molecule, determined by NMR spectroscopy, mass spectro metry and stereochemical studies, strongly suggests that there is a di rect biosynthetic relationship between the keto-and the hydroxy-mycoli c acids.