Enhancing the Potential of Enzymatic Catalysis with Light

Objetivo

One pressing challenge of chemical research is to develop new processes that responsibly use natural resources to produce added-value chiral molecules. PHOTOZYME seeks to provide solutions by combining photocatalysis, biocatalysis, and organocatalysis. These three modern strategies offer powerful tools for the sustainable preparation of chiral molecules. To date, however, they have remained largely unconnected. This proposal aims to bridge these fields in order to address major problems in asymmetric synthesis for which there is no general solution with established methods.
Specifically, we will focus on native organocatalytic intermediates formed in the enzymes active sites, exploring their potential ability to reach an excited state upon visible light absorption and thus enable new-to-nature radical reactions. Here, light will be used to program entirely new mechanisms of catalysis within enzymes with an established ground-state reactivity, thus allowing them to catalyse completely different processes than those for which they evolved. The resulting photoenzymes will be powered by absorption of photons at each catalytic cycle and will serve to infer high enantioselectivity in important radical chemistries.
Our artificial photoenzymes will be applied in four challenge areas, each representing crucial yet unsolved synthetic problems. We will develop methods to convert simple feedstock chemicals (e.g. fatty acids) into chiral building blocks. Additionally, our goal is to control the formation of multiple stereocentres in intermolecular radical processes and at remote positions of linear substrates, objectives that are exceptionally difficult to achieve with existing small-molecule systems. We also envision the design of biocatalytic radical cascades for the rapid synthesis of biorelevant chiral scaffolds directly from abundant substrates.
Overall, we aim to provide new photobiocatalytic tools that drive the sustainable production of chiral molecules.