Structure and Biocatalytic Scope of Coclaurine N -Methyltransferase
Structure and Biocatalytic Scope of Coclaurine N -Methyltransferase
复制标题
乌贼碱N-甲基转移酶的结构和生物催化范围
DOI：
10.1002/ange.201805060
复制
发表时间：
2018
影响因子：
--
通讯作者：
Bennett M
中科院分区：
文献类型：
--
作者：
Bennett M
苄基异喹啉生物碱(BIAS)是一类结构多样的植物次生代谢物，已被用于开发止痛药、抗生素、抗肿瘤药物和其他治疗药物。偏爱的生物合成通过一条从酪氨酸到(S)网状物的共同途径进行，在这一点上，途径发生了分歧。钴酸N-甲基转移酶(CNMT)是合成(S)-网状烯途径中的一个关键酶，它安装了许多BIAS生物活性所必需的甲基取代基。在本文中，我们描述了碳纳米管的第一个晶体结构，以及突变研究，定义了酶的活性部位结构。还用一系列天然和合成底物以及辅因子类似物探索了CNMT的特异性。这项研究的知识可以用来产生产生偏见或合成衍生物所需的改进的CNMT变体。
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. CoclaurineN‐methyltransferase (CNMT) is a key enzyme in the pathway to (S)‐reticulene, installing theN‐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.