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

The ascidiacea-derived strain Streptomyces 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 (1-3), featuring oxygen bridges between C-13 and C-16 (1, 2) or C-13 and C-17 (3). 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 1a and 2a exhibited antibacterial activity against Bacillus subtilis with an MIC value of 16 μg/mL, while 1b and 1c showed antifungal effects against Ceratocystis paradoxa and Corynespora cassiicola with MIC values ranging from 16 to 32 μg/mL.