Document Detail


Retrobiosynthetic approach delineates the biosynthetic pathway and the structure of the acyl chain of mycobacterial glycopeptidolipids.
MedLine Citation:
PMID:  22798073     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Archana Vats; Anil Kumar Singh; Raju Mukherjee; Tarun Chopra; Madhu Sudhan Ravindran; Debasisa Mohanty; Dipankar Chatterji; Jean-Marc Reyrat; Rajesh S Gokhale
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-07-13
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  287     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-09-03     Completed Date:  2012-11-19     Revised Date:  2013-09-03    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  30677-87     Citation Subset:  IM    
Affiliation:
CSIR-Institute of Genomics and Integrative Biology, Mall Road, Delhi 110007, India.
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MeSH Terms
Descriptor/Qualifier:
Fatty Acids / metabolism*
Glycolipids / biosynthesis*
Glycosylation
Mycobacterium smegmatis / metabolism*
Oligopeptides / biosynthesis*
Chemical
Reg. No./Substance:
0/Fatty Acids; 0/Glycolipids; 0/Oligopeptides
Comments/Corrections

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