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

Sven A. Miller, Vahe Bandarian

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1 Citation (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)11019-11026
Number of pages8
JournalJournal of the American Chemical Society
Volume141
Issue number28
DOIs
StatePublished - Jul 17 2019

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Electrochemical properties
Methionine
Enzymes
Electrolysis
Catalysis
Atoms
Secondary Metabolism
Aminobutyrates

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Analysis of Electrochemical Properties of S-Adenosyl-l-methionine and Implications for Its Role in Radical SAM Enzymes. / Miller, Sven A.; Bandarian, Vahe.

In: Journal of the American Chemical Society, Vol. 141, No. 28, 17.07.2019, p. 11019-11026.

Research output: Contribution to journalArticle

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