Genome Miningand Targeted Discovery of Twistane-ContainingAngucyclinones from Marine <i>Streptomyces phaeochromogenes</i> XSA2

Genome mining of a type II PKS biosynthetic gene cluster from marine <i>Streptomyces phaeochromogenes</i> XSA2 resulted in the discovery of 12 angucyclinone derivatives, including nine new phaeomycins A–I (<b>1</b>–<b>9</b>) and three known analogs (<b>10</b>–<b>12</b>). Phaeomycin A (<b>1</b>) 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 <b>1</b>–<b>2</b> was proposed based on bioinformatic analysis.