链霉菌CPCC 203702中抗结核分枝杆菌活性次级代谢产物的分离与鉴定  

Isolation and identification of anti-Mycobacterium tuberculosis secondary metabolites from Streptomyces sp. CPCC 203702

作　　者：张新明[1] 张德武[1] 庞旭[1] 徐建[1] 张丽蓉[1] 魏玉珍[1] 刘红宇[1] 余利岩[1] 

机构地区：[1]中国医学科学院北京协和医学院医药生物技术研究所中国药学微生物菌种保藏管理中心,北京100050

出　　处：《中国医药生物技术》2015年第4期351-355,共5页Chinese Medicinal Biotechnology

基　　金：国家自然科学基金(81402835;81373452);国家微生物资源平台(NIMR-2015-03);"重大新药创制"国家科技重大专项(2014ZX09201001-011)

摘　　要：目的研究链霉菌CPCC 203702中的抗结核分枝杆菌活性次级代谢产物。方法发酵液离心后,上清液经乙酸乙酯萃取、正相硅胶柱色谱、Sephadex LH-20凝胶柱色谱和半制备HPLC等方法进行以抗耻垢分枝杆菌活性为导向的活性化合物分离纯化,通过质谱和核磁共振波谱技术并结合文献数据进行化合物结构鉴定;分别采用平板纸片法和阿尔玛蓝法检测目的化合物的抗耻垢分枝杆菌以及抗结核分枝杆菌活性。结果从链霉菌CPCC 203702发酵液中分离到1个具有显著的抗结核分枝杆菌活性的伯尔尼霉素类化合物伯尔尼霉素C,其抗结核分枝杆菌MIC为2μg/ml;完成其核磁数据的完整归属。结论首次报道了伯尔尼霉素类抗生素具有显著的抗结核分枝杆菌活性,丰富了硫肽类抗生素的活性研究,也为抗结核药物的发现提供一个新的视角。Objective To investigate isolation and identification of anti-Mycobacterium tuberculosis secondary metabolites from Streptomyces sp. CPCC 203702.Methods The fermentation culture was separated into the supernatant and mycelia by using low-speed centrifugation. The supernatant was extracted with EtOAc, and the EtOAc extract was isolated and purified by combined use of silica gel column chromatography, Sephadex LH-20 colunm chromatography and semi-preparative HPLC. The anti-Mycobacterium tuberculosis activity was tested by MABA method. The structure of isolated pure compound was elucidated by extensive spectroscopic analyses of NMR and MS, as well as by comparing the reported NMR values in the literatures. Results Beminamycin C was isolated from the supernatant of Streptomyces sp. CPCC 203702. It showed significant anti-Mycobacterium tuberculosis activity with MIC value of 2 μg/ml.Conclusion Beminamycin C is obtained from the supematant ofStreptomyces sp. CPCC 203702 and its ^1H- and ^13C-NMR data are fully assigned for the first time. Beminamycin C shows remarkable anti-Mycobacterium tuberculosis activity which is never reported before.

关 键 词：链霉菌属 抗生素类 抗结核 伯尔尼霉素C 

分 类 号：R378.911[医药卫生—病原生物学]