Biochemical synthesis of taxanes from mevalonate  

作　　者：Jing Li Xiaonan Liu Xiaoxi Zhu Jiayu Liu Lei Zhang Nida Ahmed Jian Qi Bihuan Chen Daliang Tang Jinsheng Yu Zhijin Fan Huifeng Jiang 

机构地区：[1]Key Laboratory of Engineering Biology for Low-carbon Manufacturing,Tianjin Institute of Industrial Biotechnology,Chinese Academy of Sciences,Tianjin,300308,China [2]State Key Laboratory of Elemento-Organic Chemistry,College of Chemistry,Nankai University,Tianjin,300071,China [3]National Center of Technology Innovation for Synthetic Biology,Tianjin,300308,China [4]University of Chinese Academy of Sciences,Beijing,100049,China [5]Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development,School of Chemistry and Molecular Engineering,East China Normal University,Shanghai,200062,China

出　　处：《Synthetic and Systems Biotechnology》2024年第4期694-700,共7页合成和系统生物技术(英文)

基　　金：supported in part by the National Natural Science Foundation of China(32371499,31901026 and 32172443),China Postdoctoral Science Foundation(2019M661032);National Key R&D Program of China(2020YFA0908000 and 2022YFD1700400);the Frontiers Science Center for New Organic Matter,Nankai University(63181206);he Tianjin Development Program for Innovation and Entrepreneurship(2019-06).

摘　　要：Taxanes are kinds of diterpenoids with important bioactivities,such as paclitaxel(taxol®)is an excellent natural broad-spectrum anticancer drug.Attempts to biosynthesize taxanes have made with limited success,mainly due to the bottleneck of the low efficiency catalytic elements.In this study,we developed an artificial synthetic system to produce taxanes from mevalonate(MVA)by coupling biological and chemical methods,which comprises in vitro multi-enzyme catalytic module,chemical catalytic module and yeast cell catalytic module.Through optimizing in vitro multienzyme catalytic system,the yield of taxadiene was increased to 946.7 mg/L from MVA within 8 h and the productivity was 14.2-fold higher than microbial fermentation.By incorporating palladium catalysis,the conversion rate of Taxa-4(20),11(12)-dien-5α-yl acetate(T5α-AC)reached 48%,effectively addressing the product promiscuity and the low yield rate of T5αOH.Finally,we optimized the expression of T10βOH in yeast resulting in the biosynthesis of Taxa-4(20),11(12)-dien-5α-acetoxy-10β-ol(T5α-AC-10β-ol)at a production of 15.8 mg/L,which displayed more than 2000-fold higher than that produced by co-culture fermentation strategy.These technologies offered a promising new approach for efficient synthesis of taxanes.

关 键 词：Biochemical synthesis TAXANES PACLITAXEL Modular synthesis 

分 类 号：O62[理学—有机化学]