Jockmann, Emely;
Subrizi, Fabiana;
Mohr, Michael KF;
Carter, Eve M;
Hebecker, Pia M;
Popadić, Désirée;
Hailes, Helen C;
(2023)
Expanding the Substrate Scope of N- and O-Methyltransferases from Plants for Chemoselective Alkylation.
ChemCatChem
, Article e202300930. 10.1002/cctc.202300930.
(In press).
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Abstract
Methylation reactions are of significant interest when generating pharmaceutically active molecules and building blocks for other applications. Synthetic methylating reagents are often toxic and unselective due to their high reactivity. S‐Adenosyl‐l‐methionine (SAM)‐dependent methyltransferases (MTs) present a chemoselective and environmentally friendly alternative. The anthranilate N‐MT from Ruta graveolens (RgANMT) is involved in acridone alkaloid biosynthesis, methylating anthranilate. Although it is known to methylate substrates only at the N‐position, the closest relatives with respect to amino acid sequence similarities of over 60 % are O‐MTs catalysing the methylation reaction of caffeate and derivatives containing only hydroxyl groups (CaOMTs). In this study, we investigated the substrate range of RgANMT and a CaOMT from Prunus persica (PpCaOMT) using compounds with both, an amino‐ and hydroxyl group (aminophenols) as possible methyl group acceptors. For both enzymes, the reaction was highly chemoselective. Furthermore, generating cofactor derivatives in situ enabled the transfer of other alkyl chains onto the aminophenols, leading to an enlarged pool of products. Selected MT reactions were performed at a preparative biocatalytic scale in in vitro and in vivo experiments resulting in yields of up to 62 %.
| Type: | Article |
|---|---|
| Title: | Expanding the Substrate Scope of N- and O-Methyltransferases from Plants for Chemoselective Alkylation |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/cctc.202300930 |
| Publisher version: | https://doi.org/10.1002/cctc.202300930 |
| Language: | English |
| Additional information: | © 2023 The Authors. ChemCatChem published by Wiley-VCH GmbH This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | Anthranilate N-methyltransferase, caffeate Omethyltransferase, chemoselectivity, enzymatic alkylation, aminophenol |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Chemistry |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10176950 |
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