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One-Pot Combinatorial Biosynthesis of Glycosylated Anthracyclines by Cocultivation of Streptomyces Strains Producing Aglycones and Nucleotide Deoxysugars
- One-Pot Combinatorial Biosynthesis of Glycosylated Anthracyclines by Cocultivation of Streptomyces Strains Producing Aglycones and Nucleotide Deoxysugars
- Kim, Eunji; Song, Myoung Chong; Kim, Myoun Su; Beom, Ji Yoon; Jung, Jin A.; Cho, Hang Soo; Yoon, Yeo Joon
- Ewha Authors
- SCOPUS Author ID
- Issue Date
- Journal Title
- ACS COMBINATORIAL SCIENCE
- 2156-8952; 2156-8944
- vol. 19, no. 4, pp. 262 - 270
- cocultivation; Streptomyces; glycosylation; anthracycline; deoxysugar
- AMER CHEMICAL SOC
- SCI; SCIE; SCOPUS
- 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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