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Directed Evolution of Photoredox Powered Artificial Metalloenzymes for Stereodivergent Catalysis

Project description

Merging artificial metalloenzymes with photoredox catalysis

Artificial metalloenzymes open up new prospects for sustainable chemistry as they can produce various molecules of industrial interest more efficiently and at a lower cost than conventional chemical synthesis methods. Coupling metalloenzymes with photoredox catalysis, where a small quantity of a light-sensitive compound enables unconventional reactivity through open-shell reactive intermediates, shows great potential. Funded under the Marie Skłodowska-Curie Actions programme, the PhotoArM project will anchor a nickel catalyst inside an enzyme pocket with a nearby photocatalyst to control catalytic reactivity. This allows exploiting the secondary coordination sphere created around the new active site, which can induce reaction selectivity and improve turnover numbers.

Objective

Artificial metalloenzymes have recently emerged as powerful tools to address the ever-growing requirements of chemistry to become more efficient and sustainable. This methodology involves anchoring a reactive transition metal catalyst within a protein to exploit the secondary coordination sphere created around the new active site, which can induce selectivity in reactions and improve turnover numbers.
Concomitantly, photoredox and metallophotoredox catalysis, where a small quantity of a light sensitive compound allows non-traditional reactivity though open shell reactive intermediates, has also developed dramatically in recent years. The impressive reaction repertoire is especially synthetically attractive due to the mild conditions required and the ability to activate abundant and generally more inert functional groups. However, the current drawback to this methodology is the high levels of control needed to give the reactions their full synthetic potential.
This is where the two fields display complementarity with an unexplored interface: Photoredox Artificial Metalloenzymes.
By anchoring a nickel catalyst inside an enzyme pocket with a nearby photocatalyst, it should be possible to control catalytic reactivity by mutagenesis of residues in the secondary coordination sphere. In the proposed case of an sp3-sp3 cross-coupling reaction between a racemic amino acid derivative and bromoalkane, this could potentially allow control over both new stereocentres independently to achieve stereodivergent catalysis.
It is subsequently proposed that this methodology could be adapted to include intramolecular cross-coupling reactions, which would beneficially allow access to the valuable monocyclic β-lactam scaffold from suitably functionalised linear substrates. If possible, this may allow efficient access to diastereoisomers potentially difficult to access by other means, which may hold unexplored pharmaceutical potential.

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Topic(s)

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Funding Scheme

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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Call for proposal

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(opens in new window) H2020-MSCA-IF-2018

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Coordinator

UNIVERSITAT BASEL
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 191 149,44
Address
PETERSPLATZ 1
4051 Basel
Switzerland

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Region
Schweiz/Suisse/Svizzera Nordwestschweiz Basel-Stadt
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 191 149,44
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