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- W4283373090 abstract "Abstract The steep increase in nontuberculous mycobacteria (NTM) infections makes understanding their unique physiology an urgent health priority. NTM synthesize two polysaccharides proposed to modulate fatty acid metabolism: the ubiquitous 6-O-methylglucose lipopolysaccharide, and the 3-O-methylmannose polysaccharide (MMP) only detected in rapidly growing mycobacteria. The recent identification of a unique MMP methyltransferase implicated the adjacent genes in MMP biosynthesis. We report a wide distribution of this gene cluster in NTM, including slowly growing mycobacteria, which we reveal to produce MMP. Using a combination of MMP purification and chemoenzymatic syntheses of intermediates, we identified the biosynthetic mechanism of MMP, relying on two enzymes that we characterized biochemically and structurally: a unique α–endomannosidade that hydrolyses MMP into defined-sized mannoligosaccharides that prime the elongation of new daughter MMP chains by a rare α-(1>4)-mannosyltransferase. Therefore, MMP biogenesis occurs through a partially conservative replication mechanism, and disruption of the mechanism affected mycobacterial growth rate at low temperature." @default.
- W4283373090 created "2022-06-25" @default.
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- W4283373090 date "2022-06-22" @default.
- W4283373090 modified "2023-10-03" @default.
- W4283373090 title "Self-recycling and partially conservative replication of mycobacterial methylmannose polysaccharides" @default.
- W4283373090 doi "https://doi.org/10.21203/rs.3.rs-1362692/v1" @default.
- W4283373090 hasPublicationYear "2022" @default.
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