A tightly controlled radical-based chemistry!

Radical S-adenosyl-L-methionine (SAM) enzymes belong to a vast family of catalysts. They use the one electron reduction of a [Fe4S4] cluster to cleave SAM, producing a highly reactive 5´-deoxyadenosyl radical species. The latter in turn triggers a wide variety of radical-based reactions on substrates as different as small organic molecules, 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 pre-requisite for a broader use of these enzymes as synthetic tools. In this review are presented 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.

Structure-function of radical SAM enzymes; from mechanism to biotechnological applications. Nicolet Y. Nature Catalysis; 3 , 337–350