Biosynthesis of desosamine: Construction of a new macrolide carrying a genetically designed sugar moiety

[GRAPHICS] The appended sugars in macrolide antibiotics are indispensable to the biolo gical activities of these important drugs. In an effort to generate a set o f novel macrolide derivatives, we have created a new analogue of methymycin and neomethymycin, antibiotics produced by Streptomyces venezuelae, This a nalogue 15 carrying a different sugar, D-quinovose, instead of D-desosamine , was constructed by taking advantage of targeted gene deletion combined wi th a specific pathway-independent C-3 reduction capability of the wild type S. venezuelae.