Norwegian University of Science and Technology, Department of Biotechnology, Sem Saelandsvei 6/8, 7491 Trondheim, Norway.
Appl Environ Microbiol. 2010 Aug;76(15):4969-76. doi: 10.1128/AEM.00741-10. Epub 2010 Jun 18.
Twenty-seven marine sediment- and sponge-derived actinomycetes with a preference for or dependence on seawater for growth were classified at the genus level using molecular taxonomy. Their potential to produce bioactive secondary metabolites was analyzed by PCR screening for genes involved in polyketide and nonribosomal peptide antibiotic synthesis. Using microwell cultures, conditions for the production of antibacterial and antifungal compounds were identified for 15 of the 27 isolates subjected to this screening. Nine of the 15 active extracts were also active against multiresistant gram-positive bacterial and/or fungal indicator organisms, including vancomycin-resistant Enterococcus faecium and multidrug-resistant Candida albicans. Activity-guided fractionation of fermentation extracts of isolate TFS65-07, showing strong antibacterial activity and classified as a Nocardiopsis species, allowed the identification and purification of the active compound. Structure elucidation revealed this compound to be a new thiopeptide antibiotic with a rare aminoacetone moiety. The in vitro antibacterial activity of this thiopeptide, designated TP-1161, against a panel of bacterial strains was determined.
采用分子分类学对 27 株偏爱或依赖海水生长的海洋沉积物和海绵来源的放线菌进行了属水平分类。通过 PCR 筛选参与聚酮和非核糖体肽抗生素合成的基因,分析了它们产生生物活性次生代谢物的潜力。通过微孔培养,对 27 株经筛选的菌株中的 15 株进行了产生抗菌和抗真菌化合物的条件鉴定。在 15 种活性提取物中,有 9 种对耐多药革兰氏阳性细菌和/或真菌指示生物也具有活性,包括万古霉素耐药粪肠球菌和多药耐药白色念珠菌。对表现出强烈抗菌活性并分类为诺卡氏菌属的菌株 TFS65-07 的发酵提取物进行活性导向分离,允许鉴定和纯化活性化合物。结构阐明表明该化合物是一种具有罕见的氨基丙酮部分的新型硫肽抗生素。该硫肽,命名为 TP-1161,对一组细菌菌株的体外抗菌活性进行了测定。