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Cell Chem Biol. 2016 Feb 18;23(2):278-289. doi: 10.1016/j.chembiol.2015.11.013. Epub 2016 Jan 28.

Trehalose Polyphleates Are Produced by a Glycolipid Biosynthetic Pathway Conserved across Phylogenetically Distant Mycobacteria.

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1
CNRS, IPBS (Institut de Pharmacologie et de Biologie Structurale), UMR5089, 205 route de Narbonne, BP64182, 31077 Toulouse, France; Université de Toulouse, UPS, IPBS, 31077 Toulouse, France.
2
CNRS, IPBS (Institut de Pharmacologie et de Biologie Structurale), UMR5089, 205 route de Narbonne, BP64182, 31077 Toulouse, France; Université de Toulouse, UPS, IPBS, 31077 Toulouse, France. Electronic address: christian.chalut@ipbs.fr.

Abstract

Mycobacteria synthesize a variety of structurally related glycolipids with major biological functions. Common themes have emerged for the biosynthesis of these glycolipids, including several families of proteins. Genes encoding these proteins are usually clustered on bacterial chromosomal islets dedicated to the synthesis of one glycolipid family. Here, we investigated the function of a cluster of five genes widely distributed across non-tuberculous mycobacteria. Using defined mutant analysis and in-depth structural characterization of glycolipids from wild-type or mutant strains of Mycobacterium smegmatis and Mycobacterium abscessus, we established that they are involved in the formation of trehalose polyphleates (TPP), a family of compounds originally described in Mycobacterium phlei. Comparative genomics and lipid analysis of strains distributed along the mycobacterial phylogenetic tree revealed that TPP is synthesized by a large number of non-tuberculous mycobacteria. This work unravels a novel glycolipid biosynthetic pathway in mycobacteria and extends the spectrum of bacteria that produce TPP.

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PMID:
27028886
DOI:
10.1016/j.chembiol.2015.11.013
[Indexed for MEDLINE]
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