Engineered Biosynthesis of Disaccharide-Modified Polyene Macrolides

Recent work has uncovered genes for two glycosyltransferases that are thought to catalyze mannosylation of mycosaminyl sugars of polyene macrolides. These two genes arenypY fromPseudonocardia sp. strain P1 andpegA fromActinoplanes caeruleus . Here we analyze these genes by heterologous expression in various strains ofStreptomyces nodosus , producer of amphotericins, and inStreptomyces albidoflavus , which produces candicidins. The NypY glycosyltransferase converted amphotericins A and B and 7-oxo-amphotericin B to disaccharide-modified formsin 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.