多酶催化级联反应在天然产物酶法合成中的应用研究进展  

Research progress on application of multi-enzyme-catalyzed cascade reactions in enzymatic synthesis of natural products

作　　者：黄文倩 王迎夏 田维圣 王娟 屠鹏飞[2] 王晓晖 史社坡 刘晓 HUANG Wen-qian;WANG Ying-xia;TIAN Wei-sheng;WANG Juan;TU Peng-fei;WANG Xiao-hui;SHI She-po;LIU Xiao(Modern Research Center for Traditional Chinese Medicine,Beijing University of Chinese Medicine,Beijing 100029,China;State Key Laboratory of Natural and Biomimetic Drugs,School of Pharmaceutical Sciences,Peking University,Beijing 100191,China)

机构地区：[1]北京中医药大学中药现代研究中心,北京100029 [2]北京大学药学院天然药物及仿生药物国家重点实验室,北京100191

出　　处：《中国中药杂志》2023年第2期336-348,共13页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(82173922,81402809);北京市自然科学基金项目(7192112);天然药物及仿生药物国家重点实验室开放基金项目(K202119);中国科协青年人才托举项目(CACM-2018-QNRC1-02)。

摘　　要：酶作为一种生物催化剂,具有催化效率高、反应选择性强、目标产物专一、反应条件温和、环境友好等优点,是合成复杂有机分子的重要工具。且随着基因测序技术、分子生物学、遗传操作等技术的不断发展,酶的多样性稳步增加,可催化的反应类型也逐步多元化。在酶催化合成过程中,大多数简单反应通过单酶催化即可完成,而很多复杂反应的发生往往需要2个或以上的酶参与催化。因此,将多个酶组合到一起,构建多酶催化级联反应已逐渐成为生物化学领域的一个研究热点。如今,越来越多结构复杂的天然产物的生物合成途径得到解析,具有新颖催化活性的次级代谢酶不断被鉴定、发现并组合应用于结构多样性天然/非天然小分子的酶法合成中。该文总结了一系列多酶催化级联反应的例子,着重介绍了级联催化方法在糖类、核苷类、黄酮类、萜类、生物碱类以及手性分子等化合物合成中的应用,并对多酶催化级联方法目前存在的问题、解决对策及未来发展方向进行了讨论与展望。As a biocatalyst,enzyme has the advantages of high catalytic efficiency,strong reaction selectivity,specific target products,mild reaction conditions,and environmental friendliness,and serves as an important tool for the synthesis of complex organic molecules.With the continuous development of gene sequencing technology,molecular biology,genetic manipulation,and other technologies,the diversity of enzymes increases steadily and the reactions that can be catalyzed are also gradually diversified.In the process of enzyme-catalyzed synthesis,the majority of common enzymatic reactions can be achieved by single enzyme catalysis,while many complex reactions often require the participation of two or more enzymes.Therefore,the combination of multiple enzymes together to construct the multi-enzyme cascade reactions has become a research hotspot in the field of biochemistry.Nowadays,the biosynthetic pathways of more natural products with complex structures have been clarified,and secondary metabolic enzymes with novel catalytic activities have been identified,discovered,and combined in enzymatic synthesis of natural/unnatural molecules with diverse structures.This study summarized a series of examples of multi-enzyme-catalyzed cascades and highlighted the application of cascade catalysis methods in the synthesis of carbohydrates,nucleosides,flavonoids,terpenes,alkaloids,and chiral molecules.Furthermore,the existing problems and solutions of multi-enzyme-catalyzed cascade method were discussed,and the future development direction was prospected.

关 键 词：酶催化 生物催化 多酶催化 级联反应 

分 类 号：TQ426.97[化学工程]