Heterologous Expression of Fluostatin Gene Cluster Leads to a Bioactive Heterodimer

被引：70
作者：
Yang, Chunfang [1 ,2 ]
Huang, Chunshuai [1 ,2 ]
Zhang, Wenjun [1 ]
Zhu, Yiguang [1 ]
Zhang, Changsheng [1 ]
机构：
[1] Chinese Acad Sci, Key Lab Trop Marine Bioresources & Ecol, Guangdong Key Lab Marine Mat Med, RNAM Ctr Marine Microbiol,South China Sea Inst Oc, Guangzhou 510301, Guangdong, Peoples R China
[2] Univ Chinese Acad Sci, Beijing 100049, Peoples R China
来源：
ORGANIC LETTERS | 2015年 / 17卷 / 21期
关键词：
BIARYL NATURAL-PRODUCTS; KINAMYCIN BIOSYNTHESIS; JADOMYCIN BIOSYNTHESIS; STRUCTURE ELUCIDATION; BIOLOGICAL-PROPERTIES; LOMAIVITICIN; STREPTOMYCES; IDENTIFICATION; ANTIBIOTICS; ACTINORHODIN;
D O I：
10.1021/acs.orglett.5b02683
中图分类号：
O62 [有机化学];
学科分类号：
070303 ; 081704 ;
摘要：
The biosynthesis gene cluster (fls) for atypical angucycline fluostatins was identified from the marine derived Micromonospora rosaria SCSIO N160 and was confirmed by gene knockouts and the biochemical characterization of a bifunctional oxygenase FlsO2. The absolute configuration of the key biosynthetic intermediate prejadomycin was determined for the first time by Cu K alpha X-ray analysis. Heterologous expression of the intact fls-gene cluster in Streptomyces coelicolor YF11 in the presence of 3% sea salts led to the isolation of two new compounds: fluostatin L (1) and difluostatin A (2). Difluostatin A (2), an unusual heterodimer, exhibited antibacterial activities.
引用
收藏
页码：5324 / 5327
页数：4
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