含氮大环内酯类免疫抑制剂产生菌的系统进化分析_临床医学论文.docVIP

含氮大环内酯类免疫抑制剂产生菌的系统进化分析_临床医学论文 含氮大环内酯类免疫抑制剂产生菌的系统进化分析_临床医学论文 作者：连云阳，陈路劼；程元荣 【摘要】 目的 探讨含氮大环内酯免疫抑制剂FK506等不同产生菌之间进化关系及其次级代谢产物合成基因的水平转移。 方法 克隆不同产生菌的16S rRNA基因以及FK506等代谢产物羟化酶、甲基转移酶基因，采用Mega程序应用不同模型构建菌株系统进化树和合成酶分子进化树。 结果 代谢产物结构差异越大，其合成酶基因的进化关系越远，但是其产生菌的进化关系却可能较为接近，产生菌的进化关系与代谢产物合成酶分子进化关系不同步。 结论 此类次级代谢产物合成基因并不是菌株本身固有的，而是在菌株进化过程中同属不同种微生物之间发生基因水平转移获得的。 【关键词】 西罗莫司； 序列分析； 克隆，分子； 免疫抑制剂； 基因转移，水平 Phylogenetic Analysis of Nitrogen Immunosuppressant Producing Streptomyces Strains 　　LIAN Yunyang, CHEN Lujie, CHENG Yuanrong 　　1. Fujian Provincial Key Laboratory of Screening for Novel Microbial Products, Fujian Institute of Microbiology, Fuzhou 350007, China; 　　2.Divison of Pharmacy， Fujian Medical University, Fuzhou 350004, China ABSTRACT: Objective To reveal the evolution relationship of the producers of immunosuppressant FK506, ascomycin and sirolimus and the horizontal gene transfer of their biosynthetic genes. Methods Almost full sequences of the 16S rRNA genes and both cytochrome P450 hydroxylase and methyltransferase genes involved in the biosynthesis of FK506, ascomycin or sirolimus were cloned from different producers, respectively. Phylogenetic neighbourjoining trees, based on 16S rRNA genes, cytochrome P450 hydroxylase or methyltransferase sequences were constructed by Mega 4 programe using different models, respectively. Results Phylogenetic trees showed that the evolution relationship of the two proteins differed from that of the tested five strains. Conclusions The results of inconsistencies between the molecular evolution of biosynthetic enzyme and taxonomic relationships of the producing strains are best explained by horizontal gene transfer，namely, antibiotic biosynthesis genes transfer laterally between Streptomycetes during evolution. 　　KEY WORDS: sirolimus; sequence analysis; cloning,molecular;immunosuppressive agents; gene transfer,horizontal 福建医科大学学报 2009年9月 第43卷第5期连云阳等：含氮大环内酯类免疫抑制剂产生菌的系统进化分析化学结构相似的FK506、Sirolimus和Ascomycin（FK520）等含氮大环内酯类免疫抑制剂具有重要的实用价值，不仅在临