title: Engineered biosynthesis of disaccharide-modified polyene macrolides.
abstract: Recent work has uncovered genes for two glycosyltransferases that are thought to catalyze mannosylation of mycosaminyl sugars of polyene macrolides. These two genes are nypY from Pseudonocardia sp. strain P1 and pegA from Actinoplanes caeruleus. Here we analyze these genes by heterologous expression in various strains of Streptomyces nodosus, producer of amphotericins, and in Streptomyces albidoflavus, which produces candicidins. The NypY glycosyltransferase converted amphotericins A and B and 7-oxo-amphotericin B to disaccharide-modified forms in vivo. The enzyme did not act on amphotericin analogs lacking exocyclic carboxyl or mycosamine amino groups. Both NypY and PegA acted on candicidins. This work confirms the functions of these glycosyltransferases and provides insights into their acceptor substrate tolerance. Disaccharide-modified polyenes may have potential as less toxic antibiotics.
authors.affiliation: School of Biomolecular and Biomedical Science, Centre for Synthesis and Chemical Biology, University College Dublin, Belfield, Dublin, Ireland.
authors.forename: Eimear
authors.initials: E
authors.lastname: De Poire
authors.forename: Niamh
authors.initials: N
authors.lastname: Stephens
authors.forename: Bernard
authors.initials: B
authors.lastname: Rawlings
authors.forename: Patrick
authors.initials: P
authors.lastname: Caffrey
mesh_terms: D000192:Actinomycetales / Q000201:enzymology* / Q000235:genetics; D000900:Anti-Bacterial Agents / Q000378:metabolism; D053898:Biosynthetic Pathways / Q000235:genetics; D004187:Disaccharides / Q000378:metabolism*; D016695:Glycosyltransferases / Q000235:genetics / Q000378:metabolism*; D018942:Macrolides / Q000378:metabolism*; D060847:Metabolic Engineering / Q000379:methods*; D011090:Polyenes / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013302:Streptomyces / Q000201:enzymology* / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D004187:Disaccharides; D018942:Macrolides; D011090:Polyenes; D011994:Recombinant Proteins; D016695:Glycosyltransferases
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