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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) so far 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 such as Mycobacterium avium, 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 previously undescribed ?-endomannosidase that hydrolyses MMP into defined-sized mannoligosaccharides that prime the elongation of new daughter MMP chains by a rare ?-(1?4)-mannosyltransferase. Therefore, MMP biogenesis occurs through a partially conservative replication mechanism, whose disruption affected mycobacterial growth rate at low temperature.
Fuente: Communications biology, 2023, 6(1), 108
Año de publicación: 2023
Nº de páginas: 17
Tipo de publicación: Artículo de Revista
Url de la publicación: https://www.doi.org/10.1038/s42003-023-04448-3
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JORGE RIPOLL ROZADA
MANSO, JOSÉ A
MENDES, VERA M
VENTURA, M RITA
PEREIRA, PEDRO JOSÉ BARBOSA