Expanding the Chemical Diversity of Secondary Metabolites Produced by Two Marine-Derived Enterocin- and Wailupemycin-Producing Streptomyces Strains

[Image: see text] To expand the chemical diversity of secondary metabolites produced by two marine-derived enterocin- and wailupemycin-producing Streptomyces strains, OUCMDZ-3434 and OUCMDZ-2599, precursor feeding and solid fermentation strategies were used. Two new compounds, wailupemycins Q (1) and R (2), were isolated from the extracts of liquid and solid fermentation of OUCMDZ-3434. Furthermore, during the fermentation of OUCMDZ-3434, p-fluorobenzoic acid was added as the key biosynthetic precursor, which resulted in the isolation of eight new fluorinated enterocin and wailupemycin derivatives (3–10) and 10 previously reported analogues (11–20). From the solid fermentation extract of OUCMDZ-2599, a new sulfur-containing compound thiotetromycin B (21) and its known analogue thiotetromycin (22) were identified. Moreover, the solid fermentation strategy effectively activated the biosynthesis of siderophores (23–25) of strain OUCMDZ-2599. Compound 3 showed moderate antibacterial activity against Staphylococcus aureus and methicillin-resistant Staphylococcus aureus subsp. aureus with MIC values of 4 μg/mL. Compounds 23–25 were significantly capable of binding Fe(III).