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Retrobiosynthetic Approach Delineates the Biosynthetic Pathway and the Structure of the Acyl Chain of Mycobacterial Glycopeptidolipids

Vats, Archana and Singh, Anil Kumar and Mukherjee, Raju and Chopra, Tarun and Ravindran, Madhu Sudhan and Mohanty, Debasisa and Chatterji, Dipankar and Reyrat, Jean-Marc and Gokhale, Rajesh S (2012) Retrobiosynthetic Approach Delineates the Biosynthetic Pathway and the Structure of the Acyl Chain of Mycobacterial Glycopeptidolipids. In: Journal of Biological Chemistry, 287 (36). pp. 30677-30687.

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Official URL: http://dx.doi.org/10.1074/jbc.M112.384966

Abstract

Glycopeptidolipids (GPLs) are dominant cell surface molecules present in several non-tuberculous and opportunistic mycobacterial species. GPLs from Mycobacterium smegmatis are composed of a lipopeptide core unit consisting of a modified C-26-C-34 fatty acyl chain that is linked to a tetrapeptide (Phe-Thr-Ala-alaninol). The hydroxyl groups of threonine and terminal alaninol are further modified by glycosylations. Although chemical structures have been reported for 16 GPLs from diverse mycobacteria, there is still ambiguity in identifying the exact position of the hydroxyl group on the fatty acyl chain. Moreover, the enzymes involved in the biosynthesis of the fatty acyl component are unknown. In this study we show that a bimodular polyketide synthase in conjunction with a fatty acyl-AMP ligase dictates the synthesis of fatty acyl chain of GPL. Based on genetic, biochemical, and structural investigations, we determine that the hydroxyl group is present at the C-5 position of the fatty acyl component. Our retrobiosynthetic approach has provided a means to understand the biosynthesis of GPLs and also resolve the long-standing debate on the accurate structure of mycobacterial GPLs.

Item Type: Journal Article
Additional Information: Copyright for this article is belongs to The American Society for Biochemistry and Molecular Biology.
Keywords: TANDEM MASS-SPECTROMETRY;POLYKETIDE SYNTHASES;FATTY-ACIDS; SMEGMATIS;IDENTIFICATION;TUBERCULOSIS;SURFACE;LIPIDS; METHYLTRANSFERASE;CONSTRUCTION
Department/Centre: Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited: 07 Dec 2012 09:54
Last Modified: 07 Dec 2012 09:54
URI: http://eprints.iisc.ernet.in/id/eprint/45205

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