Light-Driven Reactions Catalyzed by Radical S-Adenosylmethionine Enzymes

Radical S-adenosylmethionine (rSAM) enzymes play a crucial role in a wide range of biotransformations with highly diverse mechanisms, but their study is frequently hindered by low in vitro activity, often due to inefficient reduction systems. In this study, we report photocatalytic approaches for rSAM enzymes by employing small-molecule sensitizers. This approach not only significantly improves enzyme activity across various rSAM enzymes but also establishes a clean and reductant-controlled system, which facilitates the exploration of intricate redox mechanisms and allows for the precise modulation of biochemical activities. Furthermore, we successfully applied this approach to develop an rSAM-enzyme-catalyzed trifluoromethylation reaction. Our findings reveal opportunities for harnessing the underexplored potential of rSAM enzymes, paving the way for further investigation of these remarkable biocatalysts in both fundamental and practical contexts.