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Orthogonal Expression of an Artificial Metalloenzyme for Abiotic Catalysis.

ABSTRACT: A cytochrome P450 was engineered 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.

SUBMITTER: Reynolds EW

PROVIDER: S-EPMC5875912 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Orthogonal Expression of an Artificial Metalloenzyme for Abiotic Catalysis.

Reynolds Evan W EW Schwochert Timothy D TD McHenry Matthew W MW Watters John W JW Brustad Eric M EM

Chembiochem : a European journal of chemical biology 20171109 24

A cytochrome P450 was engineered 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 ...[more]

PMID: 29024391

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