Catalytic Alkylation Using a Cyclic S‐Adenosylmethionine Regeneration System. Issue 13 (7th February 2017)

• Record Type: Journal Article
• Authors: Mordhorst, Silja; Siegrist, Jutta; Müller, Michael; Richter, Michael; Andexer, Jennifer N.
• Is Part Of: Angewandte Chemie international edition. Volume 56:Issue 13(2017)
• Page Start: 4037
• Page End: 4041
• Publication Date: 2017-02-07
• Subjects: cofactors -- enzyme cascades -- enzyme catalysis -- polyphosphate kinase -- S-adenosylmethionine; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201611038
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: 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, 1 H and 13 C 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. Abstract : Play it again, SAM : Biocatalytic alkylation is an emerging field in biotechnology. In addition to the discovery and engineering of highly efficient and selective methyltransferases, the development of an efficient regeneration system for the cofactor S ‐adenosylmethionine (SAM) is a prerequisite for their economic application. The development of a biomimetic in vitro SAM regeneration cycle is presented with different methyltransferases as a model system.