An Efficient Light-Driven P450 BM3 Biocatalyst

P450s are heme thiolate enzymes that catalyze the regio- and stereoselective functionalization of unactivated C–H bonds using molecular dioxygen and two electrons delivered by the reductase. We have developed hybrid P450 BM3 heme domains containing a covalently attached Ru­(II) photosensitizer in order to circumvent the dependency on the reductase and perform P450 reactions upon visible light irradiation. A highly active hybrid enzyme with improved stability and a modified Ru­(II) photosensitizer is able to catalyze the light-driven hydroxylation of lauric acid with total turnover numbers of 935 and initial reaction rate of 125 mol product/(mol enzyme/min)

Selective Light-Driven Chemoenzymatic Trifluoromethylation/Hydroxylation of Substituted Arenes

The merging of photoredox trifluoromethylation with hybrid P450 BM3 variants has enabled the selective light-driven functionalization of several arenes. This approach capitalizes on the unique photochemical properties of the Ru­(II)-diimine photosensitizer to initiate single electron transfer events. Under photoredox conditions, a CF₃ radical promoted by the d⁶ metal complex can add to arenes. In the hybrid P450 BM3 enzymes, the covalently attached Ru­(II)-diimine photosensitizer provides the necessary electrons to perform, upon visible light activation, P450 oxyfunctionalizations on the trifluoromethylated substrates