ArtMetBio · Directed Evolution of Novel Artificial Metalloenzyme Platforms for Biocatalysis
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2018-05-01 → 2020-04-30
- EU contribution
- €175,420
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
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Results in brief
Directed Evolution of Novel Artificial Metalloenzyme Platforms for Biocatalysis
Catalysis is a critical component of biochemistry and modern industry. In both of these fields, the versatility of a coordinated metal ion is frequently key to obtaining the desired catalytic function. In biology, enzymes often recruit metals to catalyze challenging transformations, such as C-H activation, nitrogen fixation, and water splitting. Despite the diversity of these reactions, natural enzymes are limited by the repertoire of bioavailable metals and ligands. In contrast, synthetic chemists can select from a wider variety of metal ions and ligands to create industrial catalysts. Thus, abiological metal catalysts enable reactions not found in nature with high enantioselectivity, versatility, and broad substrate scope. These catalysts, however, are often inferior to enzyme catalysts in terms of turnover number, efficiency, and selectivity. To take advantage of these complementary approaches, artificial metalloenzymes have emerged as a synergistic fusion of synthetic and biological catalysts. These hybrid catalysts have the potential to harness the advantages of both systems, inheriting the versatility of synthetic catalysts and the efficiency and robustness of enzymes. The objective of the ArtMetBio project is to create novel platforms for artificial metalloenzymes that optimize catalytic performance and versatility via increased cooperation between the synthetic and biological components.
Data: CORDIS, © European Union
Project objective
Artificial metalloenzymes have emerge as a fusion of synthetic and biological catalysts for environmentally friendly synthesis. These hybrid catalysts are created by tethering a catalytic metal ion or cofactor to a protein scaffold. Optimized artificial metalloenzymes have the potential to harness the advantages of both systems, inheriting the versatility of synthetic catalysts and the efficiency and robustness of enzymes. New tools, however, are required to realize the potential of artificial metalloenzymes. The objective of the ArtMetBio project is to create novel platforms for artificial metalloenzymes that optimize catalytic performance and versatility via increased cooperation between the synthetic and biological components. Now, more than ever, green catalysis is a crucial global endeavor. Our growing ability to evolve enzymes enables the use of new, unexpected protein scaffolds, opening the door to new innovative platforms. Taking advantage of directed evolution methods, this proposal outlines a strategy for repurposing two well characterized protein scaffolds to create artificial metalloenzymes for in vivo metathesis, a canonical reaction in synthetic chemistry not found in nature. Aim 1 of the project is to optimize metathesis-catalyzing enzymes, coined metathases, through directed evolution. Aim 2 will apply these metathases to engineer a biocatalytic cascade for in vivo synthesis of high-value privileged compounds. The proposed systems differ from the current state-of-the art—streptavidin and heme artificial metalloenzymes—because they are monomeric, non-toxic, and highly modular, enabling wide catalytic versatility. The proposed action has the potential to provide unique, versatile tools for synthesis and biocatalysis.
Original text from CORDIS.
Participants
- UNIVERSITAT BASEL · BaselCoordinatorSwitzerland
Links
Data: CORDIS, © European Union