Structure and Biocatalytic Scope of Coclaurine N-Methyltransferase

被引：34

作者：

Bennett, Matthew R. ^{[1
]}

Thompson, Mark L. ^{[1
]}

Shepherd, Sarah A. ^{[1
]}

Dunstan, Mark S. ^{[1
]}

Herbert, Abigail J. ^{[1
]}

Smith, Duncan R. M. ^{[1
]}

Cronin, Victoria A. ^{[1
]}

Menon, Binuraj R. K. ^{[1
]}

Levy, Colin ^{[1
]}

Micklefield, Jason ^{[1
]}

机构：

[1] Univ Manchester, Manchester Inst Biotechnol, Sch Chem, 131 Princess St, Manchester M1 7DN, Lancs, England

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2018年 / 57卷 / 33期

基金：

英国生物技术与生命科学研究理事会;

关键词：

biocatalysis; biosynthesis; mechanism; Methyltransferase; structure; COPTIS-JAPONICA; TETRAHYDROISOQUINOLINES; ENZYME; REGIOSELECTIVITY; PURIFICATION; CELLS;

D O I：

10.1002/anie.201805060

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Benzylisoquinoline alkaloids (BIAs) are a structurally diverse family of plant secondary metabolites, which have been exploited to develop analgesics, antibiotics, antitumor agents, and other therapeutic agents. Biosynthesis of BIAs proceeds via a common pathway from tyrosine to (S)-reticulene at which point the pathway diverges. Coclaurine N-methyltransferase (CNMT) is a key enzyme in the pathway to (S)-reticulene, installing the N-methyl substituent that is essential for the bioactivity of many BIAs. In this paper, we describe the first crystal structure of CNMT which, along with mutagenesis studies, defines the enzymes active site architecture. The specificity of CNMT was also explored with a range of natural and synthetic substrates as well as co-factor analogues. Knowledge from this study could be used to generate improved CNMT variants required to produce BIAs or synthetic derivatives.

引用

页码：10600 / 10604

页数：5

共 23 条

[1] Molecular cloning and characterization of coclaurine N-methyltransferase from cultured cells of Coptis japonica [J].