多功能氧化酶莨菪碱6β-羟化酶的研究进展

Research progress of the multifunctional oxidase scopolamine 6β-hydroxylase

2-酮戊二酸/Fe2+依赖的双加氧酶能够实现复杂结构化合物sp3杂化C-H键的官能化反应,并且反应条件温和,对底物具有高度的区域和立体选择性。莨菪碱6β-羟化酶(hyoscyamine 6β-hydroxylase,H6H)属于此类双加氧酶,是催化合成东莨菪碱的最后两步的关键酶,能够依次实现莨菪碱的6β-羟化和6,7位的环氧化反应。本文介绍了莨菪碱6β-羟化酶催化机制、底物谱和应用进展,对该酶转化不同结构特点底物的羟化、环氧化等反应的潜在能力进行了评估,为后续对酶的设计改造和应用研究提供理论基础。

2-ketoglutarate(2-KG)/Fe2+-dependent dioxygenases can catalyze the highly specific regio-and stereoselective functionalization of C(sp3)-H bond of complex compounds under mild reaction conditions.Hyoscyamine 6β-hydroxylase(H6H),a member of these dioxygenases,catalyzes two consecutive oxidation reactions in the synthesis of scopolamine.The first reaction is the hydroxylation of hyoscyamine to 6β-hydroxyhyoscyamine and the second is epoxidation of 6β-hydroxyhyoscyamine.This paper introduces the catalytic mechanism,substrate scope,and application of H6H and evaluates the possibility of this enzyme as a biocatalyst for the functionalization of C(sp3)-H bond in complex compounds with different structural characteristics via hydroxylation or epoxidation,providing a theoretical basis for modification and application of this enzyme.