title: One-Pot Combinatorial Biosynthesis of Glycosylated Anthracyclines by Cocultivation of Streptomyces Strains Producing Aglycones and Nucleotide Deoxysugars.
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 ε-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.
authors.affiliation: Department of Chemistry and Nanoscience, Ewha Womans University , Seoul, Republic of Korea.
authors.forename: Eunji
authors.initials: E
authors.lastname: Kim
authors.affiliation: Department of Chemistry and Nanoscience, Ewha Womans University , Seoul, Republic of Korea.
authors.forename: Myoung Chong
authors.identifier: 0000-0002-3658-025X
authors.initials: MC
authors.lastname: Song
authors.affiliation: Department of Chemistry and Nanoscience, Ewha Womans University , Seoul, Republic of Korea.
authors.forename: Myoun Su
authors.initials: MS
authors.lastname: Kim
authors.affiliation: Department of Chemistry and Nanoscience, Ewha Womans University , Seoul, Republic of Korea.
authors.forename: Ji Yoon
authors.initials: JY
authors.lastname: Beom
authors.affiliation: Department of Chemistry and Nanoscience, Ewha Womans University , Seoul, Republic of Korea.
authors.forename: Jin A
authors.initials: JA
authors.lastname: Jung
authors.affiliation: Department of Chemistry and Nanoscience, Ewha Womans University , Seoul, Republic of Korea.
authors.forename: Hang Soo
authors.initials: HS
authors.lastname: Cho
authors.affiliation: Department of Chemistry and Nanoscience, Ewha Womans University , Seoul, Republic of Korea.
authors.forename: Yeo Joon
authors.identifier: 0000-0002-3637-3103
authors.initials: YJ
authors.lastname: Yoon
mesh_terms: D018943:Anthracyclines / Q000378:metabolism*; D020650:Combinatorial Chemistry Techniques; D003837:Deoxy Sugars / Q000096:biosynthesis*; D006027:Glycosides / Q000096:biosynthesis*; D006031:Glycosylation; D016695:Glycosyltransferases / Q000378:metabolism; D009154:Mutation; D009279:Naphthacenes / Q000378:metabolism; D009711:Nucleotides / Q000378:metabolism*; D061065:Polyketides / Q000378:metabolism*; D013302:Streptomyces / Q000235:genetics / Q000378:metabolism*
chemical_list: D018943:Anthracyclines; D003837:Deoxy Sugars; D006027:Glycosides; D009279:Naphthacenes; D009711:Nucleotides; D061065:Polyketides; C027832:aklavinone; C015490:rhodomycinone; D016695:Glycosyltransferases
keywords: Streptomyces; anthracycline; cocultivation; deoxysugar; glycosylation