New Rifamycin-Type Polyketide from the Stingless Bee-Derived Micromonospora sp. TCNBRP5.7

Abstract Symbiotic Actinomycetota associated with social insects are increasingly recognized as valuable sources of bioactive secondary metabolites. In this study, we report the isolation and characterization of Micromonospora sp. TCNBRP5.7, obtained from nurse bees of the stingless bee Tetragona clavipes . Phylogenetic analyses revealed that Micromonospora strains associated with stingless bees are widely distributed across distinct clades, suggesting multiple environmental origins and acquisition routes. Micromonospora sp. TCNBRP5.7 exhibited selective antibacterial activity, inhibiting Staphylococcus aureus and Paenibacillus larvae , which guided the purification of its bioactive metabolites. Bioassay-guided fractionation and NMR/MS analyses led to the identification of two rifamycin-type polyketides: 16-desmethyl-34a-deoxy-rifamycin W ( 1 ), previously reported only from an engineered Micromonospora strain and here first reported as a naturally occurring compound, and its new analogue, 8-deoxy-16-desmethyl-34a-deoxy-rifamycin W ( 2 ). Structural elucidation showed that compound 2 lacks the phenolic OH at C-8 relative to compound 1 . Antimicrobial assays revealed that compound 1 displayed moderate activity against S. aureus (MIC 80 × 10⁻ 6 mol l⁻ 1 ), whereas neither compound inhibited P. larvae . These findings highlight Micromonospora sp. TCNBRP5.7 as a metabolically versatile strain capable of producing rare rifamycin-type metabolites, expanding the chemical diversity associated with stingless bee microbiomes. Graphical Abstract