The growing demand for environmentally benign Technologies presents significant challenges for the petrochemicals industry. This is especially true for chemical conversions involving oxidation as the reactive transition metal catalysts often employedcan be highly toxic and difficult to dispose of. Additionally, their synthetic limitations and complex syntheses further underscore the need for alternative strategies. As such, the P450 cytochromes present an attractive solution: their ability to regio- and stereospecifically oxidize an array of compounds under ambient conditions continues to fuel research into exploiting these?green? biocatalysts for commercial applications. However, a significant obstacle for practical applications using P450s is the expensive NAD(P)H cofactor, required in stoichiometric quantities for activity. The proposed work will seek to overcome this challenge by replacing NAD(P)H with the electrochemically recyclable hydride transfer complex Cp*Rh(bpy)(H2O)Cl2 (Rh), which can efficiently regenerate flavin cofactors in solution. The system will be developed for P450 BM3 which contains hydroxylase and flavin-containing reductase domains on a single polypeptide. As the protein-bound flavins hinder efficient reaction with Rh, a mutation library will be made to generate enzyme variants displaying improved activity with various similar organometallic cmpounds. In addition to catalysis, as there is no crystal structure of the reductase domain, mutants displaying activity will provide key insights into the mediator-flavin domain interaction which can be used for subsequent targeted mutagenesis to explore structure-function relationships.