Designing artificial electron transfer pathways in dioxygen-activating metalloenzymes

This thesis describes efforts to introduce new redox reactivity into two classes of dioxygen-activating enzymes. First, I investigated modified cytochrome c peroxidase (CcP). Here, a series of Trp residues were introduced between the heme active site and the surface of the enzyme to serve as a hole transfer wire. The addition of two mutations (A193W and Y229W) introduced new oxidation chemistry to CcP, as evaluated using aromatic substrate oxidation assays. This enzyme is a functional model for lignin peroxidase enzymes and provides a strong foundation for the development of new protein-based oxidation catalysts. Second, we investigated cyanobacterial aldehyde deformylating oxygenase (cAdo) enzymes. Here, we characterized and investigated three Ru-cAdo models. To provide the four electrons required for catalysis, we introduced a Ru-tris(diimine) photosensitizer to solvent exposed cysteine residues. Through NMR and GC-MS, we gained an insight into the catalytic activity of Ru-cAdo. This work highlights the nature of protein based electron transfer and points toward other underlying factors that dictate catalytic efficiency.