We have begun to develop methods to combine the diversity of reactions of organometallic complexes with the selectivity of enzymes. To do so, we have followed several approaches. In one case, we have developed cooperative chemoenzymatic reactions in which a chemical organometallic catalyst and an enzyme operate together to form one product with higher yield and selectivity than would be achieved by two using the two catalysts in two separate reactions. In a second case, we have incorporated organometallic fragments into metalloenzymes in which the metal is bound to the protein sidechains. We recently replaced the zinc of carbonic anhydrase with a rhodium-alkene fragment.
In a third set of studies, we have created artificial metalloenzymes by replacing the iron in heme proteins with noble metals. Our currently most active system is generated by replacing iron with an iridium-methyl unit. By doing so in a P450 enzyme, we have created an artificial metalloenzyme that catalyzes the insertion of carbenes into C-H bonds with activities and selectivities that rival those of natural enzymes in biosynthetic pathways. Our first studies on this topic were published in Nature and Science and signaled a new approach to create organometallic catalysts with selectivity derived from a protein matrix that can be modified in a high-throughput fashion by laboratory evolution.