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EXploring Photoinduced Enzyme pRomIscuity in the Glucose-Methanol-Choline oxidoreductase family to dEvelop New phoTocAtaLysts

Objective

Photoenzymes are rare biocatalysts that use the energy contained in photons to perform chemical reactions. To date, only one natural photocatalyst is known to have biotechnological applications; the Fatty Acid Photodecarboxylase (FAP), allowing the production of hydrocarbons from fatty acids. FAP belongs to a superfamily of enzymes called Glucose Methanol oxidoreductases (GMCox). Still, the FAP group is the only one known to perform photochemistry despite the high degree of structural similarity and presence of a photosensitive cofactor, Flavine Adenine Dinucleotide (FAD), in all GMCox.

We reason that the GMCox family could have a latent photochemical function, and we would like to exploit it. Therefore, the objective of this project is to EXplore Photoinduced Enzyme pRomIscuity in the Glucose-Methanol-Choline oxidoreductase family to dEvelop New phoTocAtaLysts (EXPERIMENTAL). To this end, we will first test the photoinduced substrate promiscuity with different GMCox using an “accelerated serendipity” approach. In a second step, we will optimize the newly discovered photoenzymatic activity by directed evolution. Finally, the enzymatic mechanism will be characterized using different biophysics approaches, ranging from time-resolved spectroscopy to serial femtosecond crystallography.

This project is inherently interdisciplinary, combining chemistry, biochemistry and biophysics to develop new photocatalysts for biotechnological purposes. For fundamental research these new photoenzymes will be an opportunity allowing the study of ultrafast processes that occur during catalysis and can only be observed with light-dependent enzymes such as electron and/or proton transfer, bond breaking ect.

In fine, the goals of EXPERIMENTAL are to provide a better appreciation of the capabilities of enzymes and meet the demand for new and sustainable methods in organic synthesis by providing with the GMCox family a toolbox for the design of new light-driven reactions.

Coordinator

COMMISSARIAT A L ENERGIE ATOMIQUE ET AUX ENERGIES ALTERNATIVES
Net EU contribution
€ 300 441,60
Address
RUE LEBLANC 25
75015 PARIS 15
France

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Region
Ile-de-France Ile-de-France Paris
Activity type
Research Organisations
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Partners (2)