Enzymatic Reactions of -Adenosyl--Methionine: Synthesis and Applications.

-adenosyl--methionine (SAM, AdoMet) is a ubiquitous biomolecule present in all living organisms, playing a central role in a wide array of biochemical reactions and intracellular regulatory pathways. It is the second most common participant in enzymatic reactions in living systems, following adenosine triphosphate (ATP). This review provides a comprehensive analysis of enzymatic reactions involving SAM, whether as a product, a reactant (cosubstrate), or as a non-consumable enzyme cofactor. The discussion encompasses various methods for SAM synthesis, including biotechnological, chemical, and enzymatic approaches. Particular emphasis is placed on the biochemical reactions where SAM functions as a cosubstrate, notably in trans-alkylation reactions, where it acts as a key methyl group donor. Beyond methylation, SAM also serves as a precursor for the synthesis of other molecular building blocks, which are explored in a dedicated section. The review also addresses the role of SAM as a non-consumable cofactor in enzymatic processes, highlighting its function as a prosthetic group for certain protein enzymes and its ability to form complexes with ribozymes. In addition, bioorthogonal systems involving SAM analogues are discussed. These systems employ engineered enzyme-cofactor pairs designed to enable highly selective interactions between target SAM analogues and specific enzymes, facilitating precise reactions even in the presence of other SAM-dependent enzymes. The concluding section explores practical applications of SAM analogues, including their use as selective inhibitors in clinical medicine and as components of reporter systems.