Taxonomic group: bacteria / Actinobacteria
(Phylum: Actinobacteria)
NCBI PubMed ID: 22798073Publication DOI: 10.1074/jbc.M112.384966Journal NLM ID: 2985121RPublisher: Baltimore, MD: American Society for Biochemistry and Molecular Biology
Correspondence: Gokhale RS <rsg
igib.res.in>
Institutions: CSIR-Institute of Genomics and Integrative Biology, Delhi, India, Université Paris Descartes, Faculté de Médecine Paris Descartes, INSERM, U570, Paris, France, Department of Biotechnology, CSIR-North East Institute of Science and Technology, Jorhat, India, Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, India, Jawarharlal Nehru Centre for Advanced Scientific Research, Jakkur, India
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 C26-C34 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.
fatty acid, Mycobacteria, lipids, acyl carrier protein, polyketides, fatty acyl AMP ligase, hydroxylation, polyketide synthase
Structure type: oligomer
Location inside paper: Fig.1, bottom structure
Compound class: glycolipopeptide
Contained glycoepitopes: IEDB_136105,IEDB_225177,IEDB_885823
Methods: DNA sequencing, DNA techniques, TLC, acid hydrolysis, anion-exchange chromatography, MALDI-TOF MS, radiolabeling, HPLC, affinity chromatography, column chromatography, cell growth, enzymatic assay, centrifugation, Q-TOF/MS
Enzymes that release or process the structure: GPL-PKS, mps1, mps2, FAAL28
Comments, role: LIP = 5-hydroxycarbonic acid with the number of carbons from 27 to 43
NCBI Taxonomy refs (TaxIDs): 246196Reference(s) to other database(s): GTC:G83121IL
Show glycosyltransferases
There is only one chemically distinct structure:
Found 
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