Hasegawa, J.-Y.; Lehnert, N.

J. Am. Chem. Soc. 2017, 139, 17265-17268, 10.1021/jacs.7b10154

Myoglobin reconstituted with iron porphycene catalyzes the cyclopropanation of styrene with ethyl diazoacetate. Compared to native myoglobin, the reconstituted protein significantly accelerates the catalytic reaction and the kcat/Km value is 26-fold enhanced. Mechanistic studies indicate that the reaction of the reconstituted protein with ethyl diazoacetate is 615-fold faster than that of native myoglobin. The metallocarbene species reacts with styrene with the apparent second-order kinetic constant of 28 mM–1 s–1 at 25 °C. Complementary theoretical studies support efficient carbene formation by the reconstituted protein that results from the strong ligand field of the porphycene and fewer intersystem crossing steps relative to the native protein. From these findings, the substitution of the cofactor with an appropriate metal complex serves as an effective way to generate a new biocatalyst.

Hyster, T.K.; Ward, T.R.

Angew. Chem. Int. Ed. 2016, 55, 7344-7357, 10.1002/anie.201508816

Artificial metalloenzymes have received increasing attention over the last decade as a possible solution to unaddressed challenges in synthetic organic chemistry. Whereas traditional transition‐metal catalysts typically only take advantage of the first coordination sphere to control reactivity and selectivity, artificial metalloenzymes can modulate both the first and second coordination spheres. This difference can manifest itself in reactivity profiles that can be truly unique to artificial metalloenzymes. This Review summarizes attempts to modulate the second coordination sphere of artificial metalloenzymes by using genetic modifications of the protein sequence. In doing so, successful attempts and creative solutions to address the challenges encountered are highlighted.