Photoinduced Electron Transfer in a Radical SAM Enzyme Generates an S-Adenosylmethionine Derived Methyl Radical

Hao Yang, Stella Impano, Eric M. Shepard, Christopher D. James, William E. Broderick, Joan B. Broderick*, Brian M. Hoffman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


Radical SAM (RS) enzymes use S-adenosyl-l-methionine (SAM) and a [4Fe-4S] cluster to initiate a broad spectrum of radical transformations throughout all kingdoms of life. We report here that low-temperature photoinduced electron transfer from the [4Fe-4S]1+ cluster to bound SAM in the active site of the hydrogenase maturase RS enzyme, HydG, results in specific homolytic cleavage of the S-CH3 bond of SAM, rather than the S-C5′ bond as in the enzyme-catalyzed (thermal) HydG reaction. This result is in stark contrast to a recent report in which photoinduced ET in the RS enzyme pyruvate formate-lyase activating enzyme cleaved the S-C5′ bond to generate a 5′-deoxyadenosyl radical, and provides the first direct evidence for homolytic S-CH3 bond cleavage in a RS enzyme. Photoinduced ET in HydG generates a trapped CH3 radical, as well as a small population of an organometallic species with an Fe-CH3 bond, denoted ωM. The CH3 radical is surprisingly found to exhibit rotational diffusion in the HydG active site at temperatures as low as 40 K, and is rapidly quenched: whereas 5′-dAdo is stable indefinitely at 77 K, CH3 quenches with a half-time of ∼2 min at this temperature.

Original languageEnglish (US)
Pages (from-to)16117-16124
Number of pages8
JournalJournal of the American Chemical Society
Issue number40
StatePublished - Oct 9 2019

ASJC Scopus subject areas

  • General Chemistry
  • Biochemistry
  • Catalysis
  • Colloid and Surface Chemistry


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