催化混杂性驱动的酶功能重塑  

Catalytic Promiscuity-driven Redesign of Enzyme Functions

作　　者：曲戈 孙周通 QU Ge;SUN Zhou-tong(Tianjin Institute of Industrial Biotechnology,Chinese Academy of Sciences,Tianjin 300308)

机构地区：[1]中国科学院天津工业生物技术研究所,天津300308

出　　处：《生物技术通报》2023年第4期1-9,共9页Biotechnology Bulletin

基　　金：国家自然科学基金项目(32171474,32171268,31900909);天津市自然科学基金(21JCJQJC00110);中国科学院青年创新促进会(2021175)。

摘　　要：作为生物催化剂,酶蛋白介导的生化反应具有条件温和、绿色环保等优点。然而相比化学催化剂,天然酶功能的局限性制约了它在生物制造领域的广泛应用。前期研究表明,酶蛋白除了催化专一性外,同时还展现出混杂性的一面,可在特定条件下催化非天然模式反应。这一特性为酶分子功能重塑提供了新思路,可用来指导人工酶设计,拓展天然酶的催化边界,实现新颖酶促反应类型,以扩大酶催化应用场景。本文从酶催化功能混杂性背后可能的进化机制入手,综述了当前诱导酶催化功能混杂性的常用策略,如定向进化、构象动力学、反应条件诱导及祖先酶重构等技术,并从催化机制、构效关系及适应性进化等多个角度,结合近年来相关研究实例,探讨了催化功能混杂性背后的分子机制,为突破天然酶促反应局限性、创制催化非天然反应的高效人工酶元件提供参考。As biocatalysts,the reactions directed by enzymes can be conducted in a green and sustainable fashion under mild conditions.However,compared to the conversional chemical catalysts,functional limitations of native enzymes restrict their broad applications in biomanufacturing.Previous studies reveal that enzymes also have catalytic promiscuities in addition to catalytic specificity,which are able to catalyze non-natural reactions.This property sheds light on the enzyme redesign,which can be used to guide the design of artificial enzymes,expand the catalytic boundaries of natural enzymes,achieve novel enzymatic reaction types,and broaden the application scenarios of enzyme catalysis.Based on the evolutionary mechanism of catalytic promiscuity,this review summarized the common strategies used for inducing promiscuities,including directed evolution,conformational dynamics,manipulating reaction conditions,ancestor enzyme reconstruction.This review also explored the molecular mechanism behind the catalytic promiscuity in the view of catalytic mechanism,structure-function relationship and adaptive evolution combined with recent relevant study cases.It may provide a reference for breaking through the limitations of natural enzymatic reactions and creating efficient artificial enzyme components that catalyze unnatural reactions.

关 键 词：催化混杂性 定向进化 理性设计 酶工程 生物催化 

分 类 号：Q814[生物学—生物工程]