원문정보
초록
영어
Narbomycin produced from Streptomyces venezuelae ATCC 15439 is composed of polyketide macrolactone ring and D-desosamine as a deoxysugar moiety, which acts as an important determinant of its antibacterial activity. For the generation of glycosylated derivatives of narbomycin, a mutant strain of S. venezuelae was engineered by deletion of TDP-D-desosamine biosynthetic gene cluster and heterologous expression of different sugar biosynthetic gene cassettes and the substrate-flexible glycosyltransferase DesVII. As a result, novel glycosylated derivatives of narbomycin were produced by S. venezuelae. The structures of newly produced narbomycin derivatives were confirmed through nuclear magnetic resonance spectroscopy and mass spectroscopy analysis and subsequently their antibacterial activities were evaluated in vitro against erythromycin-susceptible and -resistant Staphylococcus aureus and Enterococcus faecium. Novel derivatives which are substituted with L-rhamnose and 3-O-demethyl-D-chalcose, respectively, are demonstrated greater antibacterial activity than narbomycin and the clinically relevant erythromycin.