Analysis of a new mannosyltransferase required for the synthesis of phosphatidylinositol mannosides and lipoarbinomannan reveals two lipomannan pools in corynebacterineae

Lea-Smith, David J. ORCID: https://orcid.org/0000-0003-2463-406X, Martin, Kirstee L., Pyke, James S., Tull, Dedreia, McConville, Malcolm J., Coppel, Ross L. and Crellin, Paul K. (2008) Analysis of a new mannosyltransferase required for the synthesis of phosphatidylinositol mannosides and lipoarbinomannan reveals two lipomannan pools in corynebacterineae. Journal of Biological Chemistry, 283 (11). pp. 6773-6782. ISSN 0021-9258

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Abstract

The cell walls of the Corynebacterineae, which includes the important human pathogen Mycobacterium tuberculosis, contain two major lipopolysaccharides, lipoarabinomannan (LAM) and lipomannan (LM). LAM is assembled on a subpool of phosphatidylinositol mannosides (PIMs), whereas the identity of the LM lipid anchor is less well characterized. In this study we have identified a new gene (Rv2188c in M. tuberculosis and NCgl2106 in Corynebacterium glutamicum) that encodes a mannosyltransferase involved in the synthesis of the early dimannosylated PIM species, acyl-PIM2, and LAM. Disruption of the C. glutamicum NCgl2106 gene resulted in loss of synthesis of AcPIM2 and accumulation of the monomannosylated precursor, AcPIM1. The synthesis of a structurally unrelated mannolipid, Gl-X, was unaffected. The synthesis of AcPIM2 in C. glutamicum ΔNCgl2106 was restored by complementation with M. tuberculosis Rv2188c. In vivo labeling of the mutant with [3H]Man and in vitro labeling of membranes with GDP-[3H]Man confirmed that NCgl2106/Rv2188c catalyzed the second mannose addition in PIM biosynthesis, a function previously ascribed to PimB/Rv0557. The C. glutamicum ΔNCgl2106 mutant lacked mature LAM but unexpectedly still synthesized the major pool of LM. Biochemical analyses of the LM core indicated that this lipopolysaccharide was assembled on Gl-X. These data suggest that NCgl2106/Rv2188c and the previously studied PimB/Rv0557 transfer mannose residues to distinct mannoglycolipids that act as precursors for LAM and LM, respectively.

Item Type: Article
Uncontrolled Keywords: biochemistry,molecular biology,cell biology ,/dk/atira/pure/subjectarea/asjc/1300/1303
Faculty \ School: University of East Anglia Research Groups/Centres > Theme - ClimateUEA
Faculty of Science > School of Biological Sciences
UEA Research Groups: Faculty of Science > Research Groups > Molecular Microbiology
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Depositing User: LivePure Connector
Date Deposited: 01 Jul 2026 11:46
Last Modified: 01 Jul 2026 13:05
URI: https://ueaeprints.uea.ac.uk/id/eprint/103576
DOI: 10.1074/jbc.M707139200

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