Heterologous Expression of Fluostatin Gene Cluster Leads to a Bioactive Heterodimer

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• 作者：Chunfang Yang ; Chunshuai Huang ; Wenjun Zhang ; Yiguang Zhu ; Changsheng Zhang
• 刊名：Organic Letters
• 出版年：2015
• 出版时间：November 6, 2015
• 年：2015
• 卷：17
• 期：21
• 页码：5324-5327
• 全文大小：352K
• ISSN：1523-7052

文摘

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伪 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.