Genotype-driven isolation of enterocin with novel bioactivities from mangrove-derived Streptomyces qinglanensis 172205

• DOI: 10.1007/s00253-015-6574-5
• Publication Date: 2015-04-16T05:55:17Z
• Authors: Dong-Bo Xu; Min Ma; Zi-Xin Deng; Kui Hong
• Keywords: Bridged-Ring Compounds; 0301 basic medicine; Amyloid beta-Peptides; Genotype; Cell Survival; Antineoplastic Agents; Hep G2 Cells; Streptomyces; Biosynthetic Pathways; 03 medical and health sciences; Tandem Mass Spectrometry; Environmental Microbiology; Humans; HeLa Cells

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 (Aβ1-42) fibrillation and moderate cytotoxicity against HeLa and HepG2 for the first time.