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Updated: Oct 10, 2026

Sequence-specific Labeling of Nucleic Acids and Proteins with Methyltransferases and Cofactor Analogues
Published on: November 22, 2014
Beyond methylation: (re)generation and application of SAM analogs
Philipp Germer1, Arne Hoffmann2, Michael K F Mohr1
1Institute of Pharmaceutical Sciences, University of Freiburg, Albertstr. 25, 79104 Freiburg, Germany. jennifer.andexer@pharmazie.uni-freiburg.de.
Abstract:
Covering: 2021 to 2026Methyltransferases (MTs) using S-adenosyl-L-methionine (SAM) and its analogs enable highly selective alkylation reactions. Until lately, broader application was limited by the inefficiency of SAM regeneration and laborious synthesis of SAM analogs. Recent advances in enzymatic in situ supply and regeneration overcome these barriers, facilitating progress toward in vivo alkylation, advanced MT-based labeling in cells as well as application in preparative synthesis. We summarize advances in one-step regeneration, biomimetic multi-enzyme pathways, and engineered whole-cell systems that (re)generate SAM analogs from methionine analogs, alkanethiols, haloalkanes and related alkylation reagents, covering the period from 2021 to 2026. Cofactor modifications include variations at the methyl unit, amino acid moiety, and nucleobase to expand scope, enhance stability and offer orthogonality in complex reaction mixtures. Together, these advances extend transferase chemistry beyond methylation, opening new avenues in biocatalysis, drug discovery, synthetic-method development, and synthetic biology.
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