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Reprogramming Proteins and Enzymes for Transition Metal Catalysis

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Technical Report,01 Jul 2014,30 Jun 2017

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University of Chicago Chicago United States

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Controlling the selectivity of chemical reactions and conducting these reactions in biological systems, where they could have a transformative impact, stand as key challenges in synthetic chemistry. Artificial metalloenzymes ArMs could achieve these goals by combining the reactivity of synthetic metal catalysts and the adaptability and efficiency of enzymes. This proposal describes the development of ArMs generated from protein or enzyme scaffolds and metal catalysts bearing reactive anchoring groups. Ensconcing such cofactors within structurally defined yet genetically mutable scaffolds will provide exquisite control of their reactivity. The impact of this control on catalysis will be studied, and ArMs will be evolved to promote challenging chemical transformations. Ultimately, these ArMs could enable chemistry typically conducted in the confines of flasks and reactors to operate in cells and living organisms. Objectives i. Establish efficient syntheses of dirhodium tetracarboxylate and manganese terpy cofactors, and develop robust methods for covalent modification of proteins and enzymes with these cofactors to generate ArMs. ii. Evolve the proposed dirhodium and manganese terpy ArMs to enable site-specific C-H insertion reactions. iii. Develop cofactor activation approaches that exploit reactive oxygen species ROS and the reactivity of natural enzymes to enable in vivo ArM formation and catalysis During the final funding period, our study on the evolution of dirhodium ArM evolution was completed. This involved refining the previously reported evolution protocol, and developing a second protocol for evolution of immobilized ArMs. A study on the effects of scaffold dynamics on ArM selectivity was also completed and accepted for publication.

Subject Categories:

  • Biochemistry
  • Inorganic Chemistry
  • Physical Chemistry

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