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Related Concept Videos

Phase II Reactions: Methylation Reactions01:17

Phase II Reactions: Methylation Reactions

829
Methylation is a phase II biotransformation process involving the attachment of a methyl group to a substrate. Enzymes known as methyltransferases orchestrate this reaction.
The mechanism of methylation unfolds in two stages. The first stage sees a methyltransferase enzyme facilitating the transfer of a methyl group from S-adenosylmethionine (SAM) to the substrate, forming S-adenosylhomocysteine (SAH). The second stage involves further metabolism of SAH into homocysteine, which can be recycled...
829

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Recent advances in methyltransferase biocatalysis.

Matthew R Bennett1, Sarah A Shepherd1, Victoria A Cronin1

  • 1School of Chemistry & Manchester Institute of Biotechnology, University of Manchester, 131 Princess Street, Manchester M1 7DN, United Kingdom.

Current Opinion in Chemical Biology
|March 5, 2017
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Summary

Methyltransferase enzymes are engineered for synthetic applications, utilizing S-adenosyl-L-methionine analogs for novel alkylation reactions. Advances include enhanced production and improved enzyme selectivity for broader biocatalysis.

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Area of Science:

  • Biocatalysis and Synthetic Biology
  • Enzyme Engineering
  • Metabolic Engineering

Background:

  • Methyltransferases are crucial enzymes catalyzing methylation of diverse substrates.
  • Natural methyltransferases have limitations in synthetic applications.

Purpose of the Study:

  • Review recent advances in engineering methyltransferases for synthetic chemistry.
  • Highlight the use of S-adenosyl-L-methionine analogs and non-native substrates.
  • Discuss strategies for enhancing enzyme production and selectivity.

Main Methods:

  • Metabolic engineering for increased S-adenosyl-L-methionine production.
  • Enzymatic synthesis of S-adenosyl-L-methionine analogs.
  • Structure-guided mutagenesis for enzyme selectivity improvement.
  • Application in multi-enzyme cascade reactions.

Main Results:

  • Engineered methyltransferases catalyze methylation and broader alkylation reactions with S-adenosyl-L-methionine analogs.
  • Enhanced in vivo production of S-adenosyl-L-methionine.
  • Improved enzyme selectivity through directed evolution and mutagenesis.
  • Successful deployment in multi-enzyme cascades.

Conclusions:

  • Methyltransferase engineering offers a versatile platform for synthetic chemistry.
  • S-adenosyl-L-methionine analogs expand the biocatalytic scope of methyltransferases.
  • Future research should focus on further expanding substrate scope and reaction diversity.