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Production of a New Thiopeptide Antibiotic, TP-1161, by a Marine Nocardiopsis Species

机译:海洋诺卡氏菌物种生产一种新的硫肽抗生素TP-1161

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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.
机译:使用分子分类学,将27种海洋沉积物和海绵类放线菌对海水的生长加以偏好或依赖,将其分类为属。通过PCR筛选参与聚酮化合物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产物的潜力。使用微孔培养,确定了进行此筛选的27种分离物中的15种的产生抗菌和抗真菌化合物的条件。 15种活性提取物中的9种还对多重耐药的革兰氏阳性细菌和/或真菌指示生物具有活性,包括耐万古霉素的粪肠球菌和耐多药白色念珠菌。分离活性TFS65-07的发酵提取物的活性指导分级分离,显示出很强的抗菌活性,被归类为诺卡氏菌,可以鉴定和纯化活性化合物。结构解析表明该化合物是一种新的硫肽抗生素,具有罕见的氨基丙酮部分。测定了该硫肽,命名为TP-1161,对一组细菌菌株的体外抗菌活性。

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