One-Pot Combinatorial Biosynthesis of Glycosylated Anthracyclines by Cocultivation of Streptomyces Strains Producing Aglycones and Nucleotide Deoxysugars
- 주제(키워드) cocultivation , Streptomyces , glycosylation , anthracycline , deoxysugar
- 등재 SCIE, SCOPUS
- 발행기관 AMER CHEMICAL SOC
- 발행년도 2017
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000144542
- 본문언어 영어
- Published As http://dx.doi.org/10.1021/acscombsci.6600194
초록/요약
Anthracyclines, such as doxorubicin, are effective anticancer drugs composed of a tetracyclic polyketide aglycone and one or more deoxysugar moieties, which play a critical role in their biological activity. A facile one-pot combinatorial biosynthetic system was developed for the generation of a range of glycosylated derivatives of anthracyclines. Cocultivation of Streptomyces venezuelae mutants producing two anthracycline aglycones with eight different nucleotide deoxysugar-producing S. venezuelae mutants that coexpress a substrate-flexible glycosyltransferase led to the generation of 16 aklavinone or e-rhodomycinone glycosides containing diverse deoxysugar moieties, seven of which are new. This demonstrates the potential of the one-pot combinatorial biosynthetic system based on cocultivation as a facile biological tool capable of combining diverse aglycones and deoxysugars to generate structurally diverse polyketides carrying engineered sugars for drug discovery and development.
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