Affiliation:
1. Biocatalysis Department of Biotechnology Delft University of Technology Van der Maasweg 9 2629 HZ Delft The Netherlands
2. Institute of Pharmaceutical Sciences Pharmaceutical and Medicinal Chemistry University of Freiburg Albertstraße 25 79104 Freiburg Germany
3. Institute of Pharmaceutical Sciences Pharmaceutical Bioinformatics University of Freiburg Hermann-Herder-Straße 9 79104 Freiburg Germany
Abstract
AbstractS‐Adenosyl‐l‐methionine (SAM)‐dependent methyltransferases (MTs) are highly chemoselective enzymes grouped in C‐, N‐, O‐, S‐ and halide MTs, depending on the (hetero) atom that acts as the methyl group acceptor. So far, OMTs present the largest group, including many well investigated candidates. The catechol OMT from mammals such as from Rattus norvegicus (RnCOMT) is involved in the metabolism of neurotransmitters like dopamine. It is known to methylate the hydroxyl of the catechol ring in the 3 position. There are also reports showing that the regioselectivity of different COMTs can vary leading to different products with methyl groups in the 3 and or 4 positions. Nevertheless, there was only O‐methylation reported for COMTs. Another related MT, the caffeate OMT involved in the lignin biosynthesis of plants has also been reported as a chemoselective enzyme. In nature, S‐methylation is a rare phenomenon with different methyl donors being involved in the methyl transfer onto sulfur atoms. Several SAM‐dependent MTs are identified as S‐methyltransferases (SMTs), these are involved in salvaging pathways and xenobiotic metabolism of cells. Here, we report a new function of three OMTs; RnCOMT, a COMT from Myxococcus xanthus (MxSafC), and a CaOMT from Prunus persica (PpCaOMT) with acceptance towards different aromatic thiol substrates with up to full conversion.
Funder
European Research Council
Deutsche Forschungsgemeinschaft
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Catalysis