Identification of a novel protein with a role in lipoarabinomannan biosynthesis in mycobacteria
Author
Kovacevic, S; Anderson, D; Morita, YS; Patterson, J; Haites, R; McMillan, BNI; Coppel, R; McConville, MJ; Billman-Jacobe, HDate
2006-04-07Source Title
JOURNAL OF BIOLOGICAL CHEMISTRYPublisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INCUniversity of Melbourne Author/s
McConville, Malcolm; Billman-Jacobe, Helen; PATTERSON, JOHN; ANDERSON, DIANNE; MORITA, YASUHIRO; HAITES, RUTH ELIZABETH; MCMILLAN, BENJAMIN NEIL IAN; Haites, RuthAffiliation
Biochemistry And Molecular BiologyMetadata
Show full item recordDocument Type
Journal ArticleCitations
Kovacevic, S., Anderson, D., Morita, Y. S., Patterson, J., Haites, R., McMillan, B. N. I., Coppel, R., McConville, M. J. & Billman-Jacobe, H. (2006). Identification of a novel protein with a role in lipoarabinomannan biosynthesis in mycobacteria. JOURNAL OF BIOLOGICAL CHEMISTRY, 281 (14), pp.9011-9017. https://doi.org/10.1074/jbc.M511709200.Access Status
This item is currently not available from this repositoryDescription
C1 - Journal Articles Refereed
Abstract
All species of Mycobacteria synthesize distinctive cell walls that are rich in phosphatidylinositol mannosides (PIMs), lipomannan (LM), and lipoarabinomannan (LAM). PIM glycolipids, having 2-4 mannose residues, can either be channeled into polar PIM species (with 6 Man residues) or hypermannosylated to form LM and LAM. In this study, we have identified a Mycobacterium smegmatis gene, termed lpqW, that is required for the conversion of PIMs to LAM and is highly conserved in all mycobacteria. A transposon mutant, Myco481, containing an insertion near the 3' end of lpqW exhibited altered colony morphology on complex agar medium. This mutant was unstable and was consistently overgrown by a second mutant, represented by Myco481.1, that had normal growth and colony characteristics. Biochemical analysis and metabolic labeling studies showed that Myco481 synthesized the complete spectrum of apolar and polar PIMs but was unable to make LAM. LAM biosynthesis was restored to near wild type levels in Myco481.1. However, this mutant was unable to synthesize the major polar PIM (AcPIM6) and accumulated a smaller intermediate, AcPIM4. Targeted disruption of the lpqW gene and complementation of the initial Myco481 mutant with the wild type gene confirmed that the phenotype of this mutant was due to loss of LpqW. These studies suggest that LpqW has a role in regulating the flux of early PIM intermediates into polar PIM or LAM biosynthesis. They also suggest that AcPIM4 is the likely branch point intermediate in polar PIM and LAM biosynthesis.
Keywords
Biochemistry and Cell Biology not elsewhere classified ; Biological SciencesExport Reference in RIS Format
Endnote
- Click on "Export Reference in RIS Format" and choose "open with... Endnote".
Refworks
- Click on "Export Reference in RIS Format". Login to Refworks, go to References => Import References