大环内酯类化合物产生菌的基因筛选及其代谢产物研究  

Gene Screening of Macrolide-producing Strain and Its Metabolites

作　　者：江宏磊[1] 方志锴[1] 陈名洪[1] 彭飞 江红[1] 连云阳[1] JIANG Hong lei;FANG Zhi kai;CHEN Ming hong;PENG Fei;JIANG Hong;LIAN Yun yang(Fujian Institute of Microbiology,Fujian Provincial Key Laboratory of Screening for Novel Microbial Products,Fuzhou 350007,China;Quanzhou Medical College,Department of Pharmacy,Quanzhou 362100,China)

机构地区：[1]福建省微生物研究所福建省新药(微生物)筛选重点实验室,福州350007 [2]泉州医学高等专科学校药学系,泉州362100

出　　处：《天然产物研究与开发》2017年第11期1895-1899,共5页Natural Product Research and Development

基　　金：福建省自然科学基金(2015J01291);福建省海洋高新项目(2016-25);福建省微生物分析检测公共服务平台建设(2013Y2003);福建省化药平台项目(2014Y2001)

摘　　要：应用Ⅰ型聚酮合酶(PKS-I)基因筛选体系从32株海洋放线菌中寻找大环内酯类化合物的潜在产生菌,通过DNA序列相似性比对从5株阳性菌株中筛选获得了游动放线菌Actinoplanes sp.FIM060065。采用HPLC制备色谱从该菌株发酵液中分离纯化得到一个大环内酯类化合物FW060065,紫外、质谱以及核磁共振波谱分析表明它与台勾霉素B同质,药敏实验表明其对艰难梭菌、消化链球菌、双歧杆菌等革兰氏阳性厌氧菌显示出较强的抗菌能力。本研究通过基因筛选获得了台勾霉素的产生菌及其相应的代谢产物,为Ⅰ型聚酮合酶基因与大环内酯类化合物之间的联系提供了证据。The type I polyketide synthase(PKS I)gene screening system was applied to search potential producer of macrolide from32marine actinomycete strains.Based on DNA sequences alignment,the Actinoplanes sp.FIM060065was acquired from5positive strains.One macrolide FW060065was isolated and purified from the fermentation broth of the strain by pre HPLC chromatography,and was identified to be tiacumicin B by UV,MS and NMR spectral date.Drug sensitivity test showed that FW060065exhibited obvious antibacterial ability against gram positive anaerobic bacteria such as Clostridium difficile,Peptostreptococcus anaerobius and Bifidobacterium bifidum.In this study,the tiacumicin producing strain and its relevant metabolite was obtained by gene screening,which compelling evidence was provided for the relationship between PKS I gene and macrolide.

关 键 词：大环内酯类化合物 聚酮合酶 基因筛选 代谢产物 台勾霉素 

分 类 号：R978.1[医药卫生—药品]