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.