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 language | English (US) |
|---|---|
| Pages (from-to) | 11019-11026 |
| Number of pages | 8 |
| Journal | Journal of the American Chemical Society |
| Volume | 141 |
| Issue number | 28 |
| DOIs | |
| State | Published - Jul 17 2019 |
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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 journal › Article
}
TY - JOUR
T1 - Analysis of Electrochemical Properties of S-Adenosyl-l-methionine and Implications for Its Role in Radical SAM Enzymes
AU - Miller, Sven A.
AU - Bandarian, Vahe
PY - 2019/7/17
Y1 - 2019/7/17
N2 - 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.
AB - 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.
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U2 - 10.1021/jacs.9b00933
DO - 10.1021/jacs.9b00933
M3 - Article
C2 - 31283208
AN - SCOPUS:85070024390
VL - 141
SP - 11019
EP - 11026
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
SN - 0002-7863
IS - 28
ER -