Discovery of thiazostatin siderphores from Streptomyces sp. HMU0027 with a genomic DNA-based PCR assay targeting nonribosomal peptide synthetase

作     者：刘发旺 周梦洁 金晶 杨小燕 张英涛 马明 杨东辉 Fawang Liu;Mengjie Zhou;Jing Jin;Xiaoyan Yang;Yingtao Zhang;Ming Ma;Donghui Yang

作者机构：北京大学医学部药学院天然药物及仿生药物国家重点实验室北京100191 

出 版 物：《Journal of Chinese Pharmaceutical Sciences》 (中国药学（英文版）)

年 卷 期：2017年第26卷第10期

页      面：737-746页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 10[医学] 

基　　金：The National Natural Science Foundation of China(Grant No.81573326 Grant No.81673332) 

主　　题：Genome mining Nonribosomal peptide synthetase Siderophore Strain prioritization Thiazostation 

摘      要：Nonribosomal peptides （NRPs） represent a large family of natural products with great diversities of chemical structures and biological activities. The peptide backbones of NRPs are synthesized by nonribosomal peptide synthetases （NRPSs） that minimally consist of one adenylation （A） domain, one peptidyl carrier protein （PCP） and one condensation （C） domain. In this study, we carded out a PCR screening and identified 21 ＂positive＂ strains from 100 actinomycete strains with the degenerate primers designed from the conserved sequences of A domains of NRPSs. One of the 21 ＂positive＂ strains, Streptomyces sp. HMU0027, was selected for large-scale fermentation （9 L） based on HPLC analysis, and subsequent isolation and structural elucidation afforded seven NRPS-synthesized thiazostatin siderophore analogues （1-7）. Compound 1 was a new compound containing an unusual linkage between a phenolate siderophore and a sugar moiety. These results laid the foundation for further biosynthetic research of these thiazostatin analogues and highlighted the power of genome mining technologies based on biosynthetic knowledge in NRP discovery.