Pannansamycins A–K: Benzenic Ansamycins with Antioxidant Activity Isolated from Streptomyces sp. LR417

Ansamycins constitute a structurally distinctive class of macrolactams characterized by the 3-amino-5-hydroxybenzoic acid (AHBA) starter unit and a broad spectrum of pharmacological activities. Genome mining of the rhizosphere-derived Streptomyces sp. LR417 revealed a cryptic ansamycin biosynthetic gene cluster (pas) that remained transcriptionally silent under standard laboratory culture conditions. A combinatorial activation strategy, integrating the constitutive overexpression of pathway-specific positive regulators with AHBA precursor supplementation, successfully unlocked the biosynthetic potential of this cluster, affording 11 new pentaketide ansamycins, pannansamycins A-K (1-11). Compound 1 displayed potent radical-scavenging activity, while compounds 2 and 3 displayed moderate radical-scavenging and lipoxygenase inhibitory activities. These findings expand the structural diversity of the ansamycin family and provide new scaffolds with antioxidant potential worthy of further investigation.