A common mechanism for the biosynthesis of methoxy and cyclopropyl mycolic acids in Mycobacterium tuberculosis

摘要: Mycobacterium tuberculosis produces three classes of mycolic acids that differ primarily in the presence and nature oxygen-containing substituents distal portion of the meromycolate branch. The methoxymycolate series has a methoxy group adjacent to methyl branch, addition cyclopropane proximal position. Using gene for enzyme introduces (cma1) as probe, we have cloned sequenced cluster genes coding four highly homologous transferases (mma1–4). When introduced into smegmatis, this conferred ability synthesize methoxymycolates. By determining structure produced following expression each these genes individually combination, elucidated biosynthetic steps responsible production major mma4 product (MMAS-4) catalyzes an unusual S-adenosyl-l-methionine-dependent transformation cis-olefin into secondary alcohol with MMAS-3 O-methylates secondary form corresponding ether, MMAS-2 a cis-cyclopropane position methoxy series. similarity reactions enzymes catalyze them suggests some structural diversity acids results from different chemical fates common cationic intermediate, which turn group an olefinic mycolate precursor.