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Updated: Mar 7, 2026
Sequence-specific Labeling of Nucleic Acids and Proteins with Methyltransferases and Cofactor Analogues
Published on: November 22, 2014
Catalytic Alkylation Using a Cyclic S-Adenosylmethionine Regeneration System
Silja Mordhorst1, Jutta Siegrist1, Michael Müller1
1Institute of Pharmaceutical Sciences, University of Freiburg, Albertstrasse 25, 79104, Freiburg, Germany.
Researchers developed a biomimetic cyclic cascade system for S-Adenosylmethionine-dependent methyltransferases. This innovation enables cofactor regeneration using only methionine and polyphosphate, advancing biocatalysis for pharmaceutical applications.
Area of Science:
- Biocatalysis
- Enzyme Engineering
- Organic Chemistry
Background:
- S-Adenosylmethionine-dependent methyltransferases are crucial for specific alkylation in synthesizing pharmaceuticals.
- Their industrial application is hindered by the absence of efficient cofactor regeneration systems.
Purpose of the Study:
- To develop a biomimetic, polyphosphate-based cyclic cascade system for methyltransferase cofactor regeneration.
- To enable catalytic cofactor precursor regeneration for methylation and ethylation reactions.
Main Methods:
- Development of a polyphosphate-based cyclic cascade system.
- Utilizing HPLC analysis to monitor methylation and ethylation reactions.
- Employing 1H and 13C NMR spectroscopy to identify the methyl donor and reaction selectivity.
Main Results:
- The system demonstrated catalytic regeneration of the cofactor precursor adenosine.
- Successful methylation and ethylation of selected substrates were achieved.
- Methionine was confirmed as the methyl donor, and reaction selectivity was elucidated.
Conclusions:
- The developed cyclic cascade system overcomes cofactor regeneration limitations for methyltransferases.
- This biomimetic approach paves the way for economical and sustainable biocatalytic applications.
- This research is a significant step towards environmentally friendly methyltransferase utilization.
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