Genome Mining and Targeted Discovery of Twistane-Containing Angucyclinones from Marine Streptomyces phaeochromogenes XSA2

Genome mining of a type II PKS biosynthetic gene cluster from marine Streptomyces phaeochromogenes XSA2 resulted in the discovery of 12 angucyclinone derivatives, including nine new phaeomycins A-I (1-9) and three known analogs (10-12). Phaeomycin A (1) contains a unique phthalide moiety connected to a rare twistane skeleton that has not been previously identified in natural products. The chemical structures of the isolated compounds were established via extensive spectroscopic and X-ray crystal-lographic analyses. A plausible biosynthetic pathway for 1-2 was proposed based on bioinformatic analysis.