title: Novel rhamnosyltransferase involved in biosynthesis of serovar 4-specific glycopeptidolipid from Mycobacterium avium complex.
abstract: Glycopeptidolipids (GPLs) are one of the major glycolipid components present on the surface of Mycobacterium avium complex (MAC) that belong to opportunistic pathogens distributed in the natural environment. The serovars of MAC, up to around 30 types, are defined by the variable oligosaccharide portions of the GPLs. Epidemiological studies show that serovar 4 is the most prevalent type, and the prognosis of pulmonary disease caused by serovar 4 is significantly worse than that caused by other serovars. However, little is known about the biosynthesis of serovar 4-specific GPL, particularly the formation of the oligosaccharide portion that determines the properties of serovar 4. To investigate the biosynthesis of serovar 4-specific GPL, we focused on one segment that included functionally unknown genes in the GPL biosynthetic gene cluster of a serovar 4 strain. In this segment, a putative hemolytic protein gene, hlpA, and its downstream gene were found to be responsible for the formation of the 4-O-methyl-rhamnose residue, which is unique to serovar 4-specific GPL. Moreover, functional characterization of the hlpA gene revealed that it encodes a rhamnosyltransferase that transfers a rhamnose residue via 1→4 linkage to a fucose residue of serovar 2-specific GPL, which is a key pathway leading to the synthesis of oligosaccharide of serovar 4-specific GPL. These findings may provide clues to understanding the biological role of serovar 4-specific GPL in MAC pathogenicity and may also provide new insights into glycosyltransferase, which generates structural and functional diversity of GPLs.
authors.affiliation: Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases, 4-2-1 Aobacho, Higashimurayama, Tokyo 189-0002, Japan. yujim@nih.go.jp
authors.forename: Yuji
authors.initials: Y
authors.lastname: Miyamoto
authors.forename: Tetsu
authors.initials: T
authors.lastname: Mukai
authors.forename: Takashi
authors.initials: T
authors.lastname: Naka
authors.forename: Nagatoshi
authors.initials: N
authors.lastname: Fujiwara
authors.forename: Yumi
authors.initials: Y
authors.lastname: Maeda
authors.forename: Masanori
authors.initials: M
authors.lastname: Kai
authors.forename: Seiko
authors.initials: S
authors.lastname: Mizuno
authors.forename: Ikuya
authors.initials: I
authors.lastname: Yano
authors.forename: Masahiko
authors.initials: M
authors.lastname: Makino
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002236:Carbohydrate Conformation; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D006017:Glycolipids / Q000096:biosynthesis*; D006020:Glycopeptides / Q000096:biosynthesis*; D016695:Glycosyltransferases / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D015269:Mycobacterium avium Complex / Q000145:classification / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D012703:Serotyping
chemical_list: D001426:Bacterial Proteins; D006017:Glycolipids; D006020:Glycopeptides; D016695:Glycosyltransferases
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