title: Regiocomplementary O-Methylation of Catechols by Using Three-Enzyme Cascades.
abstract: S-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 O-methyltransferase 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.
authors.affiliation: Institute of Pharmaceutical Sciences, University of Freiburg, Albertstrasse 25, 79104, Freiburg, Germany.
authors.forename: Jutta
authors.initials: J
authors.lastname: Siegrist
authors.affiliation: Laboratory for Biointerfaces, Empa. Swiss Federal Laboratories for Materials Science and Technology, Lerchenfeldstrasse 5, 9014, St. Gallen, Switzerland.
authors.forename: Simon
authors.initials: S
authors.lastname: Aschwanden
authors.affiliation: Institute of Pharmaceutical Sciences, University of Freiburg, Albertstrasse 25, 79104, Freiburg, Germany.
authors.forename: Silja
authors.initials: S
authors.lastname: Mordhorst
authors.affiliation: Laboratory for Biointerfaces, Empa. Swiss Federal Laboratories for Materials Science and Technology, Lerchenfeldstrasse 5, 9014, St. Gallen, Switzerland.|AVSV, Blarerstrasse 2, 9001, St. Gallen, Switzerland.
authors.forename: Linda
authors.initials: L
authors.lastname: Thöny-Meyer
authors.affiliation: Laboratory for Biointerfaces, Empa. Swiss Federal Laboratories for Materials Science and Technology, Lerchenfeldstrasse 5, 9014, St. Gallen, Switzerland. michael.richter@igb.fraunhofer.de.|Fraunhofer Institute for Interfacial Engineering and Biotechnology (IGB), Branch BioCat, Schulgasse 11a, 94315, Straubing, Germany. michael.richter@igb.fraunhofer.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Richter
authors.affiliation: Institute of Pharmaceutical Sciences, University of Freiburg, Albertstrasse 25, 79104, Freiburg, Germany. jennifer.andexer@pharmazie.uni-freiburg.de.
authors.forename: Jennifer N
authors.initials: JN
authors.lastname: Andexer
mesh_terms: D000818:Animals; D001105:Archaea / Q000201:enzymology / Q000378:metabolism; D019843:Archaeal Proteins / Q000378:metabolism; D002394:Catechol O-Methyltransferase / Q000378:metabolism*; D002396:Catechols / Q000737:chemistry / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D008715:Methionine / Q000378:metabolism; D008716:Methionine Adenosyltransferase / Q000378:metabolism*; D008745:Methylation; D009699:N-Glycosyl Hydrolases / Q000378:metabolism*; D010100:Oxygen / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D012436:S-Adenosylmethionine / Q000378:metabolism; D013053:Spectrophotometry; D013237:Stereoisomerism
chemical_list: D019843:Archaeal Proteins; D002396:Catechols; D012436:S-Adenosylmethionine; D008715:Methionine; D002394:Catechol O-Methyltransferase; D008716:Methionine Adenosyltransferase; D009699:N-Glycosyl Hydrolases; D010100:Oxygen
keywords: S-adenosylmethionine; biotransformations; cofactors; methyltransferases; multi-enzyme reactions