Isolation and Biological Activity of Mutgriseorhodins D1 and D2, Two Shunt Products in the Rubromycin Biosynthetic Pathway.

Rubromycins constitute a unique group of aromatic polyketides with diverse biological activities. Two novel rubromycin analogs, mutgriseorhodins D1 and D2 (1 and 2) with a new pyrrole-2,5-dione ring, were generated by the heterologous expression of the grhM-deleted grh gene cluster in Streptomyces albus J1074. Their structures were elucidated by the analysis of HRMS, NMR, calculated 13C chemical shifts, and ECD calculations. Compound 2 displayed potent anti-inflammatory effects in LPS-induced BV2 microglial cells by inhibiting the NF-κB pathway and promoting M2 polarization, highlighting its potential as a promising lead compound.