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Asymmtric Copper(I) Catalysis in Artificial Metalloenzymes

Project description

Novel chemical transformations in enzymatic catalysis

Copper is an essential trace element that plays a vital role in many biological processes and is important for the proper functioning of certain proteins in the body. Copper is often coordinated by amino acid residues in the protein, forming copper-binding sites. Such sites are encountered in various enzymes that catalyse biochemical reactions, including oxidation-reduction reactions and electron transfer processes. Funded by the Marie Skłodowska-Curie Actions programme, the Cu-CATARMs project aims to create an efficient artificial metalloenzyme capable of performing new-to-nature transformations. The idea is to recruit copper (II) species to the enzyme and reduce it to copper(I), offering a new strategy for organic chemistry and material science.

Objective

The proposal that Cu-CATARMs (Asymmetric Copper(I) Catalysis in Artificial Metalloenzymes) aims to design and develop a proficient artificial metalloenzyme which contains a low oxidation state copper (Cu(I)) center, enabling a series of enantioselective new-to-nature transformations in a protein environment.
The Roelfes group has been engaged in creation of LmrR based ARMs for the asymmetric copper-catalyzed new-to-nature reactions. Reliable approaches have been developed by the Roelfes group to efficiently recruited the copper(II) species to the LmrR pore, either introducing metal binding unnatural amino acids through in vivo stop codon suppression or supramolecular assembly via the stacking interaction between tryptophan moieties and metal complex. Our approach is enabled by reducing the copper(II) center which is chelated by anchoring moiety of LmrR to copper(I) center with mild and efficient reductants in situ (objective 1). This design of copper(I) catalysis in LmrR based artificial metalloenzyme will be exploited to develop the following objectives: Objective 2. Asymmetric conjugate addition of alkynes; Objective 3. Asymmetric intramolecular cyclopropanation; Objective 4. Apart from developing the novel methodologies, we will also devote ourselves to reveal the detailed mechanism, aiming to provide theoretical guidance for future works. Overall, the successful development of Cu-CATARMs project will represent a proficient strategy to apply low oxidation state transition metals in enzyme catalysis. The results of the project will inspire the development of C-C/C-N bond formation reactions through copper(I) catalysis in ARMs and offer new strategy for the organic chemistry and material communities when planning a synthetic route for a specific target.

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Topic(s)

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2022-PF-01

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Coordinator

RIJKSUNIVERSITEIT GRONINGEN
Net EU contribution

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€ 203 464,32
Address
Broerstraat 5
9712CP Groningen
Netherlands

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Activity type
Higher or Secondary Education Establishments
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Total cost

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