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Analysis of Electrochemical Properties of S‑Adenosyl‑l‑methionine and Implications for Its Role in Radical SAM Enzymes

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journal contribution
posted on 25.06.2019, 00:00 by Sven A. Miller, Vahe Bandarian
S-Adenosyl-l-methionine (SAM) is the central cofactor in the radical SAM enzyme superfamily, responsible for a vast number of transformations in primary and secondary metabolism. In nearly all of these reactions, the reductive cleavage of SAM is proposed to produce a reactive species, 5′-deoxyadenosyl radical, which initiates catalysis. While the mechanistic details in many cases are well-understood, the reductive cleavage of SAM remains elusive. In this manuscript, we have measured the solution peak potential of SAM to be ∼−1.4 V (v SHE) and show that under controlled potential conditions, it undergoes irreversible fragmentation to the 5′-deoxyadenosyl radical. While the radical intermediate is not directly observed, its presence as an initial intermediate is inferred by the formation of 8,5′-cycloadenosine and by H atom incorporation into 5′-deoxyadenosine from solvent exchangeable site. Similarly, 2-aminobutyrate is also observed under electrolysis conditions. The implications of these results in the context of the reductive cleavage of SAM by radical SAM enzymes are discussed.