Journal
ORGANIC LETTERS
Volume 17, Issue 21, Pages 5324-5327Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.orglett.5b02683
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Funding
- NSFC [31125001, 31290233]
- Guangdong Province [2015A030308013, GD2012-D01-002, GD2012-D01-001]
- Chinese Academy of Sciences [XDA11030403]
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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.
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