CSDB: Search results

Taxonomic group: bacteria / Actinobacteria (Phylum: Actinobacteria)
Associated disease: infection due to Mycobacterium marinum [ICD11: XN8RB

]

NCBI PubMed ID: 21803773
Journal NLM ID: 2985121R
Publisher: Baltimore, MD: American Society for Biochemistry and Molecular Biology
Correspondence: laurent.kremer

univ-montp2.fr; yann.guerardel

univ-lille1.fr
Institutions: Université de Lille 1, Unité de Glycobiologie Structurale et Fonctionnelle, F-59650 Villeneuve d'Ascq, France

We have recently established the fine structure of the glycan backbone of lipooligosaccharides (LOS-I to LOS-IV) isolated from Mycobacterium marinum, a close relative of Mycobacterium tuberculosis. These studies culminated with the description of an unusual terminal N-acylated monosaccharide that confers important biological functions to LOS-IV, such as macrophage activation that may be relevant to granuloma formation. It was, however, also suggested that the lipid moiety was required for LOSs to exert their immunomodulatory activity. Herein, using highly purified LOSs from M. marinum, we have determined through a combination of mass spectrometric and NMR techniques, the structure and localization of the fatty acids composing the lipid moiety. The occurrence of two distinct polymethyl-branched fatty acids presenting specific localizations is consistent with the presence of two highly related polyketide synthases (Pks5 and Pks5.1) in M. marinum, and presumably involved in the synthesis of these fatty acyl chains. In addition, a bioinformatic search permitted us to identify a set of enzymes potentially involved in the biosynthesis or transfer of these lipids to the LOS trehalose unit. These include MMAR_2343, a member of the polyketide-associated protein (Pap) family, that acylates trehalose-based glycolipids in M. marinum. The participation of MMAR_2343 to LOS assembly was demonstrated using a M. marinum mutant carrying a transposon insertion in the MMAR_2343 gene. Disruption of MMAR_2343 resulted in a severe LOS breakdown, indicating that MMAR_2343, designated hereafter PapA4, fulfills the requirements for LOS acylation and assembly.

NMR, lipooligosaccharides, MS, Mycobacterium marinum

Structure type: oligomer
Location inside paper: p.3387, fig.8
Compound class: LOS
Contained glycoepitopes: IEDB_114701,IEDB_136105,IEDB_137477,IEDB_142488,IEDB_144998,IEDB_146664,IEDB_153543,IEDB_167188,IEDB_174332,IEDB_189517,IEDB_225177,IEDB_742521,IEDB_885823,IEDB_983931,SB_192

Methods: 13C NMR, 1H NMR, GC-MS, MALDI-MS, MS/MS, genetic methods, nESI-QFTICR MS
Biosynthesis and genetic data: genetic data
Comments, role: the trehalose core of the major LOS is substituted by two 2,4-dimethylhexadecanoate chains in the C4 position of terminal Glc residue and in the C2 position of internal Glc residue and by one 2,4-dimethyl-2-pentadecenoate in the C6 position of the terminal Glc residue.

NCBI Taxonomy refs (TaxIDs): 1781
Show glycosyltransferases

There is only one chemically distinct structure:

[1*]OC[C@H]1O[C@H](O[C@H]2O[C@H](CO)[C@@H](O[C@@H]3O[C@H](CO)[C@@H](O)[C@H](O[C@@H]4O[C@H](CO)[C@@H](O)[C@H](O[C@@H]5O[C@@H](C)[C@H](O[C@@H]6OC[C@@H](O[C@H]7O[C@H](C)[C@@](O)([C@@H](O)C[C@H](O[C@H]8O[C@H](C)[C@@](O)([C@@H](O)C[C@H](O[C@H]9O[C@H](C)[C@H](NC(=O)[C@@]%10(C(=O)O)N(C)C(=O)[C@H](OC)[C@@]%10(C)O)[C@H](O)[C@H]9O)[C@H](O)[C@@H](C)O)C[C@H]8O)[C@H](O)[C@@H](C)O)C[C@H]7O)[C@H](O)[C@H]6O)[C@@H](OC)[C@H]5O)[C@H]4O)[C@H]3O)[C@H](O)[C@H]2O[1*])[C@H](O)[C@@H](O)[C@@H]1O[1*]

SVG MW SMILES 3D mol Ionize

R1 = LIP