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

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.