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Structure–function relationships of radical SAM enzymes

Nature Catalysis volume 3, pages 337–350 (2020)Cite this article

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Abstract

Radical S-adenosyl-l-methionine (SAM) enzymes belong to a family of catalysts whose number of annotated sequences is still growing. Upon the one-electron reduction of a [Fe4S4] cluster, they can cleave SAM to produce a highly reactive 5′-deoxyadenosyl radical species. This radical species in turn triggers a wide variety of radical-based reactions on substrates ranging from small organic molecules to proteins, DNA or RNA. The challenging reactions they catalyse makes them very promising catalysts for diverse biotechnological applications. However, the high-energy intermediates involved require fine control of the chemistry by the protein matrix. Understanding their control mechanism is a prerequisite for a broader use of these enzymes as synthetic tools. Here I review some of the latest developments in the field, focusing on the structure–function relationship of a few examples for which three-dimensional structures, in vitro and spectroscopic data, as well as theoretical calculations, are available to better describe the close interaction between the chemistry performed and the tight control of the protein matrix.

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Fig. 1: Selected examples of reactions catalysed by radical SAM enzymes.
Fig. 2: SAM cleavage.
Fig. 3: Radical SAM dehydratase and dehydrogenase.
Fig. 4: Radical SAM methyltransferase RlmN.
Fig. 5: Radical SAM 7-carboxy-7-deazaguanine synthase QueE.
Fig. 6: Radical SAM l-tryptophan lyase NosL.
Fig. 7: Examples of promising radical SAM enzymes.

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Acknowledgements

I thank the Commissariat à l’Energie Atomique et aux Energies Alternatives for institutional support. Part of the work presented was supported by the Radis-Bio contract from the CEA/DRF-Impulsion program and the Agence Nationale pour la Recherche (ANR-16-CE29-0019).

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    Yvain Nicolet

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Nicolet, Y. Structure–function relationships of radical SAM enzymes. Nat Catal 3, 337–350 (2020). https://doi.org/10.1038/s41929-020-0448-7

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