酶促4+2和2+2环加成反应:区域与立体选择性的理解与应用  

Enzymatic(4+2)-and(2+2)-cycloaddition reactions:fundamentals and applications of regio-and stereoselectivity

作　　者：汤志军 胡友财 刘文[1] TANG Zhijun;HU Youcai;LIU Wen(State Key Laboratory of Chemical Biology,Shanghai Institute of Organic Chemistry,Chinese Academy of Sciences,Shanghai 200032,China;State Key Laboratory of Bioactive Substance and Function of Natural Medicines,Institute of Materia Medica,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100050,China)

机构地区：[1]中国科学院上海有机化学研究所,生命过程小分子调控全国重点实验室,上海200032 [2]中国医学科学院&北京协和医学院药物研究所,天然药物活性物质与功能国家重点实验室,北京100050

出　　处：《合成生物学》2024年第3期401-407,共7页Synthetic Biology Journal

基　　金：国家自然科学基金(32030002,22193070,22207116,82225042)。

摘　　要：4+2和2+2环加成反应均是构筑环结构的重要有机化学反应,在复杂天然产物、手性药物的化学合成和生物合成方面有广泛的应用。发现、发展包括4+2和2+2在内的酶促环加成反应,是当前化学生物学研究的热点之一。近期,国际、国内研究团队相继报道了多个酶促4+2和2+2环加成反应,解析了环化酶的蛋白结构和催化机制,设计了新的环化酶,或通过定向进化实现了不同类型环加成反应的区域和立体选择性调控。相关研究为采用合成生物学的策略设计和优化新型环加成酶提供了理论基础和成功范例,有利于促进酶促反应在有机合成领域的应用。The(4+2)-and(2+2)-cycloadditions are important chemical reactions for constructing ring structures,with broad applications in the chemical synthesis and biosynthesis of complex natural products and chiral drugs.The discovery and development of enzymatic cycloaddition reactions,including both(4+2)-and(2+2)-cycloadditions,are currently hot topics in the field of chemical biology.Recently,several international and domestic research groups have successively reported multiple enzymatic(4+2)-and(2+2)-cycloadditions,revealing related protein structures and enzymatic mechanisms,designing new artificial cyclases,and developed different types of regio-and selective cycloaddition reactions through protein engineering.These studies provide a theoretical basis and successful examples for the design and optimization of novel cyclases using synthetic biology strategy,and will promote applications of the enzymatic reactions in organic synthesis.

关 键 词：4+2环加成反应 2+2环加成反应 化学合成和生物合成 环化酶 定向进化 

分 类 号：Q816[生物学—生物工程]