工业微生物2023，Vol.53Issue(6)：55-62,8.DOI:10.3969/j.issn.1001-6678.2023.06.017
以组合生物合成策略为导向的C-核苷类多氧霉素的研究
Research on Novel C-nucleoside Polyoxin Guided by Combinatorial Biosynthesis Strategies
摘要
Abstract
Based on the strategy of combinatorial biosynthesis,the paper introduces the C-nucleoside in the structure of Malayamycin into the structure of polyoxin,and obtains a new type of polyoxin hybrid antibiotic with C-nucleoside.By artificially designing the structure of hybrid antibiotics,the industrial strain Streptomyces aureogenes of polyoxin was modified and corresponding mutant strains were obtained.Then,the starting genes truD and malO responsible for C-nucleoside synthesis in the biosynthesis of Malayamycin were integrated to obtain recombinant strains PA1 and PA2.The structure of the metabolites was confirmed by biological activity measurement and liquid phase high-resolution mass spectrometry(LC-HRMS)analysis.In addition,the recombinant strain PA3 was obtained by increasing the copy number of the polyoxin biosynthesis gene cluster to increase the yield of the target heterozygous antibiotic.Recombinant strains PA1 and PA2 can selectively produce pseudouridine polyoxin L with a C-nucleoside structure(Ψ-Polyoxin L),and pseudouridine polyoxin K(Ψ-Polyoxin K);Gene cluster doubling in recombinant strain PA3 Ψ-Polyoxin L and Ψ-The yield of polyoxin K was significantly increased.The production of new C-nucleoside polyoxin has laid a solid foundation for the future research on the synthesis of multiple combinations of related nucleoside antibiotics.关键词
核苷类抗生素/多氧霉素/马来亚霉素/杂合抗生素/组合生物合成Key words
nucleoside antibiotics/polyoxin/malayamycin/hybrid antibiotics/combinatorial biosynthesis引用本文复制引用
刘元园,李天竹,熊莉,龚蓉,陈文青..以组合生物合成策略为导向的C-核苷类多氧霉素的研究[J].工业微生物,2023,53(6):55-62,8.基金项目
国家自然科学基金(31970052,32170026). （31970052,32170026）
