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

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