Selective C–H bond functionalization using repurposed or artificial metalloenzymes

David M Upp, Jared C Lewis

Curr. Opin. Chem. Biol.
2017, 37, 48-56; DOI: 10.1016/j.cbpa.2016.12.027


Catalytic C–H bond functionalization has become an important tool for organic synthesis. Metalloenzymes offer a solution to one of the foremost challenges in this field, site-selective C–H functionalization, but they are only capable of catalyzing a subset of the Csingle bondH functionalization reactions known to small molecule catalysts.

To overcome this limitation, metalloenzymes have been repurposed by exploiting the reactivity of their native cofactors toward substrates not found in nature. Additionally, new reactivity has been accessed by incorporating synthetic metal cofactors into protein scaffolds to form artificial metalloenzymes. The selectivity and activity of these catalysts has been tuned using directed evolution. This review covers the recent progress in developing and optimizing both repurposed and artificial metalloenzymes as catalysts for selective C–H bond functionalization.