Radical SAM enzymes: Nature's choice for radical reactions

Broderick, Joan B.; Broderick, William E.; Hoffman, Brian M.

doi:10.1002/1873-3468.14519

Radical SAM enzymes: Nature's choice for radical reactions

Journal Article · Thu Oct 27 00:00:00 EDT 2022 · FEBS Letters

DOI:https://doi.org/10.1002/1873-3468.14519· OSTI ID:2419701

^[1]; Broderick, William E. ^[2]; Hoffman, Brian M. ^[3]

Montana State Univ., Bozeman, MT (United States); OSTI
Montana State Univ., Bozeman, MT (United States)
Northwestern Univ., Evanston, IL (United States)

Enzymes that use a [4Fe-4S]¹⁺ cluster plus S-adenosyl-L-methionine (SAM) to initiate radical reactions (radical SAM) form the largest enzyme superfamily, with over half a million members across the tree of life. This review summarizes recent work revealing the radical SAM reaction pathway, which ultimately liberates the 5´-deoxyadenosyl (5´-dAdo•) radical to perform extremely diverse, highly regio- and stereo-specific, transformations. Most surprising was the discovery of an organometallic intermediate Ω exhibiting an Fe-C5´-adenosyl bond. Ω liberates 5´-dAdo• through homolysis of the Fe-C5´ bond, in analogy to Co-C5´ bond homolysis in B12, previously viewed as biology’s paradigmatic radical generator. The 5´-dAdo• has been trapped and characterized in radical SAM enzymes via a recently-discovered photoreactivity of the [4Fe- 4S]⁺/SAM complex, and has been confirmed as a catalytically active intermediate in enzyme catalysis. The regioselective SAM S-C bond cleavage to produce 5´-dAdo• originates in the JahnTeller effect. The simplicity of SAM as a radical precursor, and the exquisite control of 5´-dAdo• reactivity in radical SAM enzymes, may be why radical SAM enzymes pervade the tree of life, while B12 enzymes are only a few.

View Accepted Manuscript (DOE)

Research Organization:: Montana State Univ., Bozeman, MT (United States)

Sponsoring Organization:: National Institutes of Health (NIH); USDOE; USDOE Office of Science (SC)

Grant/Contract Number:: SC0005404

OSTI ID:: 2419701

Alternate ID(s):: OSTI ID: 1894976

Journal Information:: FEBS Letters, Journal Name: FEBS Letters Journal Issue: 1 Vol. 597; ISSN 0014-5793

Publisher:: Federation of European Biochemical SocietiesCopyright Statement

Country of Publication:: United States

Language:: English

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