细胞色素P450酶在香精香料绿色生物合成中的应用  

Application of Cytochrome P450 in the Biosynthesis of Flavors and Fragrances

作　　者：郁慧丽 李爱涛 YU Hui-li;LI Ai-tao(State Key Laboratory of Biocatalysis and Enzyme Engineering,School of Life Sciences,Hubei University,Wuhan 430062)

机构地区：[1]湖北大学生命科学学院省部共建生物催化与酶工程国家重点实验室,武汉430062

出　　处：《生物技术通报》2023年第4期24-37,共14页Biotechnology Bulletin

基　　金：国家重点研发计划(2021YFC2102400);湖北省教育厅青年人才项目(郁慧丽);湖北省杰出青年基金(2020CFA072);湖北省生物催化与酶工程创新引智示范基地(2019BJH021)。

摘　　要：细胞色素P450酶是一类含亚铁血红素的蛋白超家族,来源广泛,几乎存在于所有的生命形式中。P450酶被誉为“黄金催化剂”,主要参与生物体内源物质合成、异源物质代谢及天然产物的生物合成,具有底物谱广、催化反应类型多样、催化立体专一性强等优点,使得它们在药物/毒物代谢、工程化生物合成等方面受到越来越多的关注。其中,P450酶可以实现常温、常压、中性条件下特定惰性C-H键选择性羟化,在高附加值精细化学品的生物合成中具有重要应用价值。本文介绍了P450选择性羟化的催化机制及几种常见的P450电子传递系统,并结合蛋白质工程与代谢工程,以柠檬烯含氧衍生物、诺卡酮、檀香醇、4-羟基异佛尔酮、大环内酯麝香等高附加值化合物的生物合成为例,综述了单酶催化的生物转化或全细胞从头合成的方式在天然香精香料生物合成中的探索与应用,探讨其面临的挑战并展望了其应用前景。Cytochromes P450 belong to a large superfamily of hemeproteins,which are widespread in almost all forms of life.P450s are known as“golden catalysts”,and they are mainly involved in the synthesis of endogenous substances,metabolism of xenobiotics,and biosynthesis of natural products in living organisms.P450-catalyzed reactions demonstrate various advantages including wide substrate spectrum,diverse types of catalytic reactions,and high catalytic regio-and stereospecificity,which make them increasingly attractive in drug/toxin metabolism,and engineered product biosynthesis.Among the P450 catalyzed reactions,the introduction of a hydroxyl group at a specific inert C-H bonds under mild conditions makes them highly useful in high value-added fine chemicals biosynthesis.Hereby the mechanism of selective hydroxylation of P450s and related several common types of electron transfer chain system are introduced.The biosynthesis of several natural flavors and fragrances such as limonene oxygenated derivatives,nootkatone,santalol,4-hydroxyisophorone,and macrocyclic musk,which are catalyzed by single enzyme-catalyzed biotransformation or whole-cell de novo biosynthesis involving protein and metabolic engineering,are reviewed.Finally,the challenges and prospects of their practical applications are discussed.

关 键 词：细胞色素P450酶 香精香料 生物合成 蛋白质工程 代谢工程 

分 类 号：TQ65[化学工程—精细化工]