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

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).