Abstract
Tuberculostearic acid (l0-methylstearic acid, TSA) is a major constituent of mycobacterial membrane phospholipids, and its biosynthesis involves the direct methylation of oleic acid esterified as a component of phospholipids. The methyltransferases of mycobacteria were long proposed to be involved in the synthesis of methyl-branched short-chain fatty acids, but direct experimental evidence is still lacking. In this study, we identified the methyltransferase encoded by umaA in Mycobacterium tuberculosis H37Rv as a novel S-adenosyl-l-methionine (SAM)-dependent methyltransferase capable of catalyzing the conversion of olefinic double bond of phospholipid-linked oleic acid to biologically essential TSA. Therefore, UmaA, catalyzing such modifications, offer a viable target for chemotherapeutic intervention.
We thank Dr. Rajesh S. Gokhale, Director, CSIR-Institute of Genomics and Integrative Biology (IGIB), New Delhi, for making this work possible. One of the authors (L.S.M.) wants to thank the Department of Science and Technology (DST), for their financial support under the grant numbers GAP0050 and GAP0092, and the CSIR, for providing the funds under the In House Project Scheme (LSM59). The financial support was provided by NMITLI; CSIR is also acknowledged. P.C. was supported by the University Grant Commission, Delhi, India.
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