1887

Abstract

Urdamycin A, the principal product of Tü2717, is an angucycline-type antibiotic and anticancer agent containing C-glycosidically linked -olivose. To extend knowledge of the biosynthesis of urdamycin A the authors have cloned further parts of the urdamycin biosynthetic gene cluster. Three new ORFs , and ) were identified on a 335 kb fragment, and seven new ORFs (, , , , , and ) on an 805 kb fragment. The deduced products of these genes show similarities to transporters ( and ), regulatory genes (), reductases (), cyclases () and deoxysugar biosynthetic genes (, and ). The product of shows striking sequence similarity to oxygenases (N-terminal sequence) as well as reductases (C-terminal sequence), and the deduced amino acid sequence of resembles those of glycosyltransferases. To determine the function of and , targeted gene inactivation experiments were performed. The resulting deletion mutant strains accumulated predominantly rabelomycin, indicating that UrdM is involved in oxygenation at position 12b of urdamycin A. A mutant in which had been deleted produced urdamycin I, urdamycin J and urdamycin K instead of urdamycin A. Urdamycins I, J and K are tetracyclic angucyclinones lacking a C–C connected deoxysugar moiety. Therefore UrdGT2 must catalyse the earliest glycosyltransfer step in the urdamycin biosynthetic pathway, theC-glycosyltransfer of one NDP--olivose.

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2000-01-01
2019-12-12
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