S-Adenosylmethionine: more than just a methyl donor

Area of Science:

• Biochemistry
• Enzymology
• Natural Product Biosynthesis

Background:

• S-Adenosyl-L-methionine (SAM) is a key biological molecule primarily known for methyltransfer reactions.
• SAM's versatile chemistry extends to donating other moieties and undergoing modifications before transfer.
• The sulfonium cation in SAM is crucial for various enzymatic transformations beyond simple methylation.

Purpose of the Study:

• To review recent discoveries of novel enzymes utilizing S-Adenosyl-L-methionine (SAM).
• To explore SAM-dependent enzymes that employ Lewis acid/base chemistry, distinct from radical mechanisms.
• To categorize these enzymes based on structural features and SAM's role in catalysis.

Main Methods:

• Literature review of studies published from 2000 to early 2023.
• Analysis of enzymatic mechanisms involving SAM, focusing on Lewis acid/base catalysis.
• Categorization of SAM-utilizing enzymes based on methyltransferase fold presence and SAM's function.

Main Results:

• Identification of diverse SAM-dependent enzymes with varied catalytic strategies.
• Demonstration that not all SAM-dependent enzymes are methyltransferases, despite shared structural folds.
• Highlighting enzymes that utilize SAM through Lewis acid/base interactions, expanding known reaction pathways.

Conclusions:

• Enzymatic catalysis with SAM is more diverse than previously recognized, involving varied active site chemistries.
• Novel SAM-utilizing enzymes showcase evolutionary diversification in biological catalysis.
• Understanding these enzymes offers insights into sulfonium chemistry in both biology and organic synthesis.