紫杉醇药物中间体的合成生物学研究进展theadvancein-药学学报.pdfVIP

药学学报 Acta Pharmaceutica Sinica 20 13, 48 (2): 187 192 ·187 · 紫杉醇药物中间体的合成生物学研究进展 * 伟 , 杨 燕, 郑晓东, 黄淑琼, 郭 磊, 孔建强, 程克棣 ( 中国医学科学院、北京协和医学院 物研究所, 天然药物活性物质与功能国家重点实验室、 卫生部天然 物生物合成重点实验室, 北京 100050) 摘要: 天然药物合成生物学技术的发展促进了临床上重要的抗肿瘤药物紫杉醇的异源生物合成的研究, 本 文简要综述了紫杉醇药物中间体在大肠杆菌和酿酒酵母等工程细胞中异源生物合成途径的组建、代谢调控和代 谢产物的分析及其规模化发酵生物制备的 颈问题。 关键词: 紫杉醇; 紫杉烯; 大肠杆菌; 酿酒酵母; 合成生物学 中图分类号: R93 1 文献标识码: A 文章编号: 05 13-4870 (20 13) 02-0187-06 The advance in synthetic biology: towards a microbe-derived paclitaxel intermediates * WANG Wei , YANG Yan, ZHENG Xiao-dong, HUANG Shu-qiong, GUO Lei, KONG Jian-qiang, CHENG Ke-di (State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Key Laboratory of Biosynthesis of Natural Products, Ministry of Health of PR C, Institute of Materia Medica, Chinese A cademy of Medical Sciences and Peking Union Medical College, Beijing 100050, China) Abstract: The synthetic biology matures to promote the heterologous biosynthesis of the well-known drug paclitaxel that is one of the most important and active chemotherapeutic agents for the first-line clinical treatment of cancer. This review focuses on the construction and regulation of the biosynthetic pathway of paclitaxel intermediates in both Escherichia coli and Saccharomyces cerevisiae. In particular, the review also features the early efforts to design and overproduce taxadiene and the bottleneck of scale fermentation for