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

摘要:

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。

Abstract:

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.