This dissertation describes the engineering and evolution of dirhodium artificial metalloenzymes (ArMs) for selective carbene transfer catalysis. The ArM hybrid catalyst is formed by covalent attachment of a dirhodium tetracarboxylate cofactor a prolyl oligopeptidase scaffold, which is shown to control the environment around the metal center to enable selectivity. The process of improving this scaffold-based control through multiple carbene transfer reactions has improved our understanding of this system and ArMs more broadly. Chapter 1 begins with an introduction to selective catalysis and the inspirations for ArMs. Case studies of four well-established ArM systems are then used to identify common factors that enable control over diverse cofactor reactivities. Three factors: localization of the metal center, encapsulation of the cofactor, and evolvability of the scaffold are found to be critical in this regard. Chapter 2 describes an exploration of the reactivity and selectivity enabled by the dirhodium POP ArM. A diverse set of insertion reactions are examined, including N-H, S-H, Si-H and C-H bond functionalizations, which demonstrate the scaffold’s capacity to control dirhodium catalysis. The reactions analyzed here lay the groundwork for engineering efforts in later chapters. Chapter 3 describes the directed evolution of the ArM for improved diazo coupling. The improved variants were used in a multistep, biocatalytic cascade that was possible due to scaffold-controlled chemoselectivity. Chapter 4 contains progress on the engineering of improved variants for N-H functionalization. This reaction involves an enantiodetermining proton transfer, which the ArM scaffold is found to facilitate. Finally, Chapter 5 details directed evolution and reaction engineering efforts towards improved ArM-catalyzed Si-H and C-H functionalization. The work described in each of these chapters has produced a number of highly selective ArMs and has furthered our understanding of scaffold-based control over non-native metal catalysts.