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Orthogonal Expression

Researchers in the Brustad Group, published in ChemBioChem, report the engineering of cytochrome P450 to selectively incorporate Ir(Me)-deuteroporphyrin IX (Ir(Me)-DPIX), in lieu of heme, in bacterial cells. Cofactor selectivity was altered by introducing mutations within the heme-binding pocket to discriminate the deuteroporphyrin macrocycle, in combination with mutations to the P450 axial cysteine to accommodate a pendant methyl group on the Ir(Me) center.

This artificial metalloenzyme was investigated for activity in non-native metallocarbenoid-mediated olefin cyclopropanation reactions and showed enhanced activity for aliphatic and electron-deficient olefins when compared to the native heme enzyme.

This work provides a general strategy to augment the chemical functionality of heme enzymes in cells with application towards abiotic catalysis.