Structure and biocatalytic scope of Coclaurine N-methyltransferase

Matthew R. Bennett, Mark L. Thompson, Sarah A. Shepherd, Mark S. Dunstan, Abigail J. Herbert, Duncan R. M. Smith, Victoria A. Cronin, Binuraj R. K. Menon, Colin Levy, Jason Micklefield*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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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.

Original languageEnglish
Pages (from-to)10600-10604
Number of pages5
JournalAngewandte Chemie - International Edition
Issue number33
Early online date28 Jun 2018
Publication statusPublished - 13 Aug 2018


  • biocatalysis
  • biosynthesis
  • mechanism
  • Methyltransferase
  • structure
  • UKRI
  • BB/K00199X/1
  • BB/M017702/1


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