%T An Alternative Cascade for the Selective Methylation of Catechols and Tetrahydroisoquinolines by O-Methyltransferases %V 16 %A Matthew T Salinger %A Daniel Castellano Garrido %A Eleanor D Lamming %A John M Ward %A Thomas S Moody %A Jack WE Jeffries %A Helen C Hailes %N 7 %D 2024 %I Wiley %K biocatalysis, methyltransferases, methylation, cascade, catechols %J ChemCatChem %L discovery10193493 %X Methyltransferases are gaining traction as a method to achieve greener and regioselective methylations of a wide array of substrates. In this work, a halide methyltransferase biomethylation cascade was successfully adapted with the incorporation of a methionine adenosyltransferase to generate the Sâ€adenosylâ€Lâ€methionine (SAM) methylation cofactor in situ from less costly ATP and Lâ€methionine, instead of directly adding SAM to start the cascade. Furthermore, this cascade was applied to achieve novel catechol and tetrahydroisoquinoline methylations with the Oâ€methyltransferases RnCOMT, MxSafC and NpN4OMT with high conversions and regioselectivities. In addition, the cascade was successfully trialled with the less toxic methyl group donor, methyl tosylate. %O © 2024 The Authors. ChemCatChem published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/).