title: Heterologous Expression of Fluostatin Gene Cluster Leads to a Bioactive Heterodimer.
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.
authors.affiliation: 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.|University of Chinese Academy of Sciences , 19 Yuquan Road, Beijing 100049, China.
authors.forename: Chunfang
authors.initials: C
authors.lastname: Yang
authors.affiliation: 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.|University of Chinese Academy of Sciences , 19 Yuquan Road, Beijing 100049, China.
authors.forename: Chunshuai
authors.initials: C
authors.lastname: Huang
authors.affiliation: 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.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Yiguang
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: 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.
authors.forename: Changsheng
authors.initials: C
authors.lastname: Zhang
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D005449:Fluorenes / Q000737:chemistry / Q000302:isolation & purification*; D008386:Marine Biology; D008826:Microbial Sensitivity Tests; D008847:Micromonospora / Q000737:chemistry*; D015394:Molecular Structure; D005810:Multigene Family; D048372:Streptomyces coelicolor / Q000235:genetics; D000095602:Angucyclines and Angucyclinones
chemical_list: D000900:Anti-Bacterial Agents; D005449:Fluorenes; C000605687:difluostatin A; D000095602:Angucyclines and Angucyclinones; C114113:fluostatin A; C000605686:fluostatin L