紫杉醇在酵母中的组合生物合成  

Advances of Paclitaxel Combinatorial Biosynthesis in Yeast

作　　者：王玉霞[1] 王春梅[1] 

机构地区：[1]北京中医药大学中药学院生物制药系,北京100102

出　　处：《药物生物技术》2013年第3期271-275,共5页Pharmaceutical Biotechnology

基　　金：北京中医药大学自主选题课题(No.2009JYB22-XS023)

摘　　要：紫杉醇是萜类的一种重要的次级代谢产物,是一种重要的新型抗癌药物。但由于资源紧缺、产率低等问题使得紫杉醇的价格昂贵,阻碍了紫杉醇的进一步应用。利用微生物进行组合生物合成生产紫杉醇将是一种新型的生产方式。酵母是目前用于组合生物合成研究最多和最有应用前景的宿主。文章对近年来利用酵母进行紫杉醇的组合生物合成的研究进展进行了总结,分析了目前存在的问题,并提出了将来可能的研究重点和发展方向,为研究工作者提供思路和借鉴。Taxol is a kind of plant secondary metabolites. It is also well-established as a potent antineoplastic drug because of its unique mode of action and efficacy against multiple forms of cancer. However,the further application of taxol has been delayed due to the resource shortage. As a novel mode of production,combinatorial biosynthesis,which is an approach to combine genes from different organisms to produce bioactive compounds, including plant secondary metabolites, has made some progresses. This article briefly reviews the basic information about taxol,its biosynthetic pathway and related genes, as well as the preparation. The most promising way to produce taxol might be combinatorial biosynthesis. There are a lot of advantages to use yeast as a host. This paper focuses on the progress of the taxol combinatorial biosynthesis using yeast as a host. Saccharomyces cerevisiae was the only kind of yeast hosts used in current researches. The construction of biosynthetic pathway of taxol in yeast from geranylgeranyl diphosphate to taxadiene and the early part of the whole taxoid biosynthetic pathway were deeply studied. An engineered yeast that could produce taxadiene to a relatively high level of 8.7 mg/L was built by coexpression of geranylgeranyl diphosphate synthase and taxadiene synthase,regulation of the metabolic flux and usage of codon-optimized genes. However, there was rare research on the construction of the pathway from taxa- diene to intermidiate Baccatin III or final product taxol. Therefore,a limited production of taxadien -5α- ol was obtained although a pathway from taxatiene to Taxa-4 （20）, 11 （12）-dien-5α-acetoxy-1013-ol was built in yeast. Finally, a short analysis and a brief discussion were made on current problems,future trends and possibilities.

关 键 词：紫杉醇 紫杉二烯 生物合成途径 酵母 组合生物合成 综述 

分 类 号：S791.49[农业科学—林木遗传育种]