title: Proposed pathway for the biosynthesis of serovar-specific glycopeptidolipids in Mycobacterium avium serovar 2.
abstract: Members of the Mycobacterium avium complex are distinguished by the presence of highly antigenic surface molecules called glycopeptidolipids (GPLs) and the oligosaccharide portion of the serovar-specific GPL defines the 28 serovars. Previously, the genomic region (ser2) encoding the enzymes responsible for the glycosylation of the lipopeptide core to generate the serovar-2-specific GPLs has been described. In this work, the ser2 gene clusters of M. avium serovar 2 strains 2151 and TMC 724 were fully sequenced and compared to the homologous regions of M. avium serovar 1 strain 104, M. avium subsp. paratuberculosis and M. avium subsp. silvaticum. It was also determined that 104Rg, a mutant of strain 104 that produces truncated GPLs, lost several GPL biosynthesis genes by deletion. This comparison, together with analysis of protein similarities, supports a biosynthetic model in which serovar-2-specific GPLs are synthesized from a serovar-1-specific GPL intermediate that is derived from a non-specific GPL precursor. We also identified a gene encoding an enzyme that is necessary for the biosynthesis of serovar-3- and 9-specific GPLs, but not serovar-2-specific GPLs, suggesting that the different serovars may have evolved from the acquisition or loss of genetic information. In addition, a subcluster of genes for the biosynthesis and transfer of fucose, which are needed to make serovar-specific GPLs such as those of serovar 2, is found in the non-GPL-producing M. avium subspecies paratuberculosis and silvaticum.
authors.affiliation: Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523-1682, USA.
authors.forename: Torsten M
authors.initials: TM
authors.lastname: Eckstein
authors.affiliation: Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523-1682, USA.
authors.forename: John T
authors.initials: JT
authors.lastname: Belisle
authors.affiliation: Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523-1682, USA.
authors.forename: Julia M
authors.initials: JM
authors.lastname: Inamine
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D005643:Fucose / Q000378:metabolism; D005964:Glucosyltransferases / Q000235:genetics; D006017:Glycolipids / Q000096:biosynthesis*; D006020:Glycopeptides / Q000096:biosynthesis*; D008969:Molecular Sequence Data; D005810:Multigene Family; D009162:Mycobacterium avium / Q000235:genetics / Q000378:metabolism*
chemical_list: D006017:Glycolipids; D006020:Glycopeptides; D005643:Fucose; C036655:1,3-alpha-D-glucan synthase; D005964:Glucosyltransferases