Enzymes that contain metals or metal cofactors catalyze the most challenging and fascinating transformations on earth, including methane oxidation and N₂ fixation. To support this broad range of chemical reactions, metalloenzymes have evolved with marvelous structural and functional diversity. Our group leverages the immense synthetic potential harbored in this staggering inventory of metalloenzymes to provide solutions to outstanding problems at the frontiers of chemistry and biology. Central to this research endeavor is to bring new concepts to bioinorganic catalysis by drawing inspiration from mechanistic connections between synthetic and biocatalytic systems. We develop interdisciplinary approaches that integrate organic synthesis, chemical biology, protein engineering, biochemical analysis, and computational modeling to reprogram metalloenzymes to access reaction space beyond their current catalytic repertoire. These enzymes not only provide powerful tools for numerous synthetic and biological applications, but also offer a fertile ground to enrich our fundamental knowledge of bioinorganic chemistry and enzymatic catalysis.