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One-Pot Combinatorial Biosynthesis of Glycosylated Anthracyclines by Cocultivation of Streptomyces Strains Producing Aglycones and Nucleotide Deoxysugars

Title
One-Pot Combinatorial Biosynthesis of Glycosylated Anthracyclines by Cocultivation of Streptomyces Strains Producing Aglycones and Nucleotide Deoxysugars
Authors
Kim, EunjiSong, Myoung ChongKim, Myoun SuBeom, Ji YoonJung, Jin A.Cho, Hang SooYoon, Yeo Joon
Ewha Authors
윤여준
SCOPUS Author ID
윤여준scopus
Issue Date
2017
Journal Title
ACS COMBINATORIAL SCIENCE
ISSN
2156-8952JCR Link2156-8944JCR Link
Citation
vol. 19, no. 4, pp. 262 - 270
Keywords
cocultivationStreptomycesglycosylationanthracyclinedeoxysugar
Publisher
AMER CHEMICAL SOC
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
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.
DOI
10.1021/acscombsci.6600194
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자연과학대학 > 화학·나노과학전공 > Journal papers
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