Xu Dong-Bo, Ma Min, Deng Zi-Xin, Hong Kui
Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, School of Pharmaceutical Sciences, Wuhan University, Wuhan, 430071, China.
Appl Microbiol Biotechnol. 2015 Jul;99(14):5825-32. doi: 10.1007/s00253-015-6574-5. Epub 2015 Apr 17.
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.
通过基因组序列引导，从红树林来源的新物种青蓝链霉菌172205中分离出II型聚酮合酶（PKS）天然产物肠菌素（1），并揭示了其推定的生物合成基因簇。还通过串联质谱法鉴定了其天然类似物5-脱氧肠菌素（2）和瓦卢佩霉素A-C（3-5）。通过用芳酸进行饲喂实验，证明菌株172205将部分外源性起始单元掺入基于肠菌素和瓦卢佩霉素的类似物中，因此是一种用于工程化非天然肠菌素衍生的聚酮代谢物的新型合适微生物。此外，生物学测定表明，肠菌素首次对β-淀粉样蛋白（Aβ1-42）纤维化表现出明显的抑制活性，对HeLa和HepG2具有中等细胞毒性。
