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.

Document Details

Document Type
Pub Defense Publication
Publication Date
Nov 09, 2017
Source ID
10.1002/cbic.201700397

Entities

People

  • Eric M Brustad
  • Evan W. Reynolds
  • John W. Watters
  • Matthew W. Mchenry
  • Timothy D. Schwochert

Organizations

  • Defense Advanced Research Projects Agency
  • National Science Foundation
  • National Science Foundation Directorate for Mathematical & Physical Sciences
  • University of North Carolina at Chapel Hill

Tags

Fields of Study

  • Chemistry

Readers

  • Molecular and Cellular Biochemistry
  • Organic Chemistry

Technology Areas

  • Microelectronics