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Updated: Jun 17, 2026

A High-Throughput Enzyme-Coupled Activity Assay to Probe Small Molecule Interaction with the dNTPase SAMHD1
Published on: April 16, 2021
Harnessing the Versatility of SAM-Dependent Enzymes: From Mechanism to Application
Yaming Zhao1, Shuaiqi Meng1, Mengyi Chen1
1State Key Laboratory of Microbial Technology, Ministry of Education Key Laboratory of NSLSCS, College of Life Science, Nanjing Normal University, Nanjing, China.
None:
S-Adenosyl-L-methionine (SAM) is a central biological cofactor that supplied activated methyl groups and enables a broad-spectrum biochemical transformation. Beyond canonical SN2 methyl transfer, SAM-dependent enzymes could initiate radical-mediated chemistry via reductive SAM cleavage, enabling versatile reactions from methyl transfer to alkylation, isomerization, and decarboxylation. Despite their extraordinary catalytic plasticity and potential for sustainable industrial synthesis, SAM-dependent enzymes are often limited by insufficient activity, stability, and substrate scope, necessitating further engineering. In this review, we summarize SAM-dependent enzymes into methylation and nonmethylation catalytic systems, and systematically summarize recent protein engineering efforts aimed at enhancing activity, selectivity, and stability. Together, these advances establish a unified framework for unlocking the full catalytic potential of SAM-dependent enzymes, paving the way for their integration as versatile and sustainable biocatalysts in modern chemical synthesis.
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