Heterologous Expression of Fluostatin Gene Cluster Leads to a Bioactive Heterodimer

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.