Bennett, Matthew R., Thompson, Mark L., Shepherd, Sarah A., Dunstan, Mark S., Herbert, Abigail J., Smith, Duncan R. M., Cronin, Victoria A., Menon, Binuraj R. K., Levy, Colin and Micklefield, Jason (2018) Structure and biocatalytic scope of coclaurine N-methyltransferase. Angewandte Chemie International Edition, 57 (33). pp. 10600-10604. doi:10.1002/anie.201805060

Research output not available from this repository, contact author.

Request Changes to record.

Abstract

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.

Item Type:	Journal Article
Divisions:	Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- )
Journal or Publication Title:	Angewandte Chemie International Edition
Publisher:	Wiley - V C H Verlag GmbH & Co. KGaA
ISSN:	1433-7851
Official Date:	13 August 2018
Dates:	Date Event 13 August 2018 Published 23 May 2018 Available 23 May 2018 Accepted
Volume:	57
Number:	33
Page Range:	pp. 10600-10604
DOI:	10.1002/anie.201805060
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access

Request changes or add full text files to a record

Repository staff actions (login required)

View Item