The type II polyketide synthase (PKS) natural product enterocin ( 1 ) was isolated from a mangrove-derived novel species Streptomyces qinglanensis 172205 guided by genome sequence, and its putative biosynthetic gene cluster was revealed. Its natural analogues 5-deoxyenterocin ( 2 ) and wailupemycin A–C ( 3–5 ) were also identified by tandem mass spectrometry. By feeding experiments with aryl acids, strain 172205 was proved to incorporate partial exogenous starter units into enterocin- and wailupemycin-based analogues, thus being a new and suitable microorganism for engineering unnatural enc -derived polyketide metabolites. In addition, biological assays indicated that enterocin showed obvious inhibitory activity against β-amyloid protein (Aβ 1-42 ) fibrillation and moderate cytotoxicity against HeLa and HepG2 for the first time.
Kunyu Xia,Jiaxu Shang,Jiwen Sun,Weiming Zhu,Peng Fu
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).
危险品化学品经营许可证（带存储）