One-Pot Combinatorial Biosynthesis of Glycosylated Anthracyclines by Cocultivation of Streptomyces Strains Producing Aglycones and Nucleotide Deoxysugars
| Autor: | Myoung Chong Song, Hang Soo Cho, Jin A Jung, Myoun Su Kim, Yeo Joon Yoon, Ji Yoon Beom, Eunji Kim |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Streptomyces venezuelae Glycosylation Naphthacenes Stereochemistry 01 natural sciences Streptomyces 03 medical and health sciences chemistry.chemical_compound Polyketide Deoxy Sugars Glycosyltransferase Combinatorial Chemistry Techniques Anthracyclines Nucleotide Glycosides chemistry.chemical_classification biology Nucleotides 010405 organic chemistry Chemistry Drug discovery Glycosyltransferases General Chemistry General Medicine biology.organism_classification 0104 chemical sciences 030104 developmental biology Aglycone Biochemistry Polyketides Mutation biology.protein |
| Zdroj: | ACS Combinatorial Science. 19:262-270 |
| ISSN: | 2156-8944 2156-8952 |
| DOI: | 10.1021/acscombsci.6b00194 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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