Artificial metalloenzymes ideally combine the favorable properties of natural enzymes with the high efficiency of synthetic catalysts. Inserting new metal groups into existing native proteins, however, often leads to poorer overall catalytic efficiency. To break through this limitation, Dydio et al. replaced the iron in the heme group of cytochrome P450 with iridium and subjected it to directed evolution. The enzyme catalyzed a range of reactions with kinetics similar to those of the native enzyme.