An artificial metalloenzyme with the kinetics of native enzymes

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Science  07 Oct 2016:
Vol. 354, Issue 6308, pp. 102-106
DOI: 10.1126/science.aah4427

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Something like the real thing

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. It was also able to functionalize fully unactivated C-H bonds, a reaction that previously has only been mediated by synthetic catalysts. Moreover, the artificial enzyme was stable across temperatures and scales that are used industrially.

Science, this issue p. 102


Natural enzymes contain highly evolved active sites that lead to fast rates and high selectivities. Although artificial metalloenzymes have been developed that catalyze abiological transformations with high stereoselectivity, the activities of these artificial enzymes are much lower than those of natural enzymes. Here, we report a reconstituted artificial metalloenzyme containing an iridium porphyrin that exhibits kinetic parameters similar to those of natural enzymes. In particular, variants of the P450 enzyme CYP119 containing iridium in place of iron catalyze insertions of carbenes into C–H bonds with up to 98% enantiomeric excess, 35,000 turnovers, and 2550 hours−1 turnover frequency. This activity leads to intramolecular carbene insertions into unactivated C–H bonds and intermolecular carbene insertions into C–H bonds. These results lift the restrictions on merging chemical catalysis and biocatalysis to create highly active, productive, and selective metalloenzymes for abiological reactions.

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