2. Academic Validation
  3. Heterologous Expression of Fluostatin Gene Cluster Leads to a Bioactive Heterodimer

Heterologous Expression of Fluostatin Gene Cluster Leads to a Bioactive Heterodimer

  • Org Lett. 2015 Nov 6;17(21):5324-7. doi: 10.1021/acs.orglett.5b02683.
Chunfang Yang 1 2,  Chunshuai Huang 1 2,  Wenjun Zhang 1,  Yiguang Zhu 1,  Changsheng Zhang 1
Affiliations

Affiliations

  • 1 Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, RNAM Center for Marine Microbiology, South China Sea Institute of Oceanology, Chinese Academy of Sciences , 164 West Xingang Road, Guangzhou 510301, China.
  • 2 University of Chinese Academy of Sciences , 19 Yuquan Road, Beijing 100049, China.
PMID: 26465097 DOI: 10.1021/acs.orglett.5b02683
Abstract

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 Kα 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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