Siegrist, JuttaJuttaSiegristAschwanden, SimonSimonAschwandenMordhorst, SiljaSiljaMordhorstThöny-Meyer, LindaLindaThöny-MeyerRichter, MichaelMichaelRichterAndexer, Jennifer N.Jennifer N.Andexer2022-03-052022-03-052015https://publica.fraunhofer.de/handle/publica/24296010.1002/cbic.201500410S-Adenosylmethionine (SAM)-dependent enzymes have great potential for selective alkylation processes. In this study we investigated the regiocomplementary O-methylation of catechols. Enzymatic methylation is often hampered by the need for a stoichiometric supply of SAM and the inhibitory effect of the SAM-derived byproduct on most methyltransferases. To counteract these issues we set up an enzyme cascade. Firstly, SAM was generated from l-methionine and ATP by use of an archaeal methionine adenosyltransferase. Secondly, 4-O-methylation of the substrates dopamine and dihydrocaffeic acid was achieved by use of SafC from the saframycin biosynthesis pathway in 40-70% yield and high selectivity. The regiocomplementary 3-O-methylation was catalysed by catechol Omethyltransferase from rat. Thirdly, the beneficial influence of a nucleosidase on the overall conversion was demonstrated. The results of this study are important milestones on the pathway to catalytic SAM-dependent alkylation processes.en572journal article