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Directed Evolution of Photoredox Powered Artificial Metalloenzymes for Stereodivergent Catalysis


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.

Field of science

  • /natural sciences/chemical sciences/inorganic chemistry/inorganic compounds
  • /natural sciences/chemical sciences/organic chemistry/amines
  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins/enzymes

Call for proposal

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Funding Scheme

MSCA-IF-EF-ST - Standard EF


Petersplatz 1
4051 Basel
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 191 149,44