Discovery, Structure, and Absolute Configuration of Pemacromycins A–C, Polyene Macrolides from an Ascidians-Derived Actinomycete <i>Streptomyces</i> sp. GXX01-02

The ascidiacea-derived strain <i>Streptomyces</i> sp. GXX01-02 initially yielded the antifungal polyketide-nucleoside hybrid jawsamycin. To explore further metabolic diversity, the OSMAC strategy was employed, with the rice medium extract notably exhibiting a unique UV signature that suggested the presence of distinct secondary metabolites. This led to the identification of three filipin-type polyene macrolides, pemacromycins A-C (<b>1</b>-<b>3</b>), featuring oxygen bridges between C-13 and C-16 (<b>1</b>, <b>2</b>) or C-13 and C-17 (<b>3</b>). Their structures were defined by a combination of comprehensive spectroscopic analysis, Kishi's universal NMR database, Newman projections, DP4+ probability analyses, modified Mosher's method, and Mo₂(AcO)₄-induced circular dichroism. Bioassays revealed that derivatives <b>1a</b> and <b>2a</b> exhibited antibacterial activity against <i>Bacillus subtilis</i> with an MIC value of 16 μg/mL, while <b>1b</b> and <b>1c</b> showed antifungal effects against <i>Ceratocystis paradoxa</i> and <i>Corynespora cassiicola</i> with MIC values ranging from 16 to 32 μg/mL.