Catalytic Alkylation Using a Cyclic S-Adenosylmethionine Regeneration System.
S-Adenosylmethionine-dependent methyltransferases are versatile tools for the specific alkylation of many compounds, such as pharmaceuticals, but their biocatalytic application is severely limited owing to the lack of a cofactor regeneration system. We report a biomimetic, polyphosphate-based, cyclic cascade for methyltransferases. In addition to the substrate to be methylated, only methionine and polyphosphate have to be added in stoichiometric amounts. The system acts catalytically with respect to the cofactor precursor adenosine in methylation and ethylation reactions of selected substrates, as shown by HPLC analysis. Furthermore,1H and13C NMR measurements were performed to unequivocally identify methionine as the methyl donor and to gain insight into the selectivity of the reactions. This system constitutes a vital stage in the development of economical and environmentally friendly applications of methyltransferases.
Institute of Pharmaceutical Sciences, University of Freiburg, Albertstrasse 25, 79104, Freiburg, Germany.
Silja
S
Mordhorst
Institute of Pharmaceutical Sciences, University of Freiburg, Albertstrasse 25, 79104, Freiburg, Germany.
Jutta
J
Siegrist
Institute of Pharmaceutical Sciences, University of Freiburg, Albertstrasse 25, 79104, Freiburg, Germany.
Michael
M
Müller
Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, Bio, Electro and Chemocatalysis BioCat, Straubing branch, Schulgasse 11a, 94315, Straubing, Germany.
Michael
M
Richter
Institute of Pharmaceutical Sciences, University of Freiburg, Albertstrasse 25, 79104, Freiburg, Germany.
Jennifer N
0000-0001-8238-5749
JN
Andexer
S-adenosylmethionine; cofactors; enzyme cascades; enzyme catalysis; polyphosphate kinase