HEIndividual fellowship2022–2025

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

Horizon Europe — Marie Skłodowska-Curie Actions

Duration
2022-08-15 → 2025-08-14
EU contribution
€300,442
Participants
2
Scheme
HORIZON-TMA-MSCA-PF-GF

Lines connect the coordinator with its partners.

Results in brief

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

The goal of this project is to develop new stereospecific chemical reactions using enzymes activated by light, known as photobiocatalysis. Photobiocatalysis combines the use of light with an enzyme to access new chemical reactions that are difficult or impossible to achieve with traditional methods. By using light to activate enzymes, this project aims to make chemical synthesis processes more efficient by reducing the number of steps needed and avoiding the use of harsh conditions. Enzymes are natural catalysts that operate under mild conditions and have a unique chiral environment, allowing them to selectively produce one of two mirror-image forms of a molecule (enantioselectivity). This makes them particularly useful for producing complex molecules, such as pharmaceuticals, which require high precision. The reactions developed in this project could replace traditional chemical processes, leading to more sustainable and environmentally friendly chemical production. The project roadmap involves identifying enzymes that can catalyze reactions using light and optimizing these enzymes. By expanding the capabilities of enzymes like Fatty Acid Photodecarboxylase (FAP), GMC oxidoreductase and other enzymes such as lactate monooxygenase (LMO), the project aims to provide more efficient and sustainable synthetic pathways. The research contributes to the broader objective of enhancing the use of biocatalysis in chemical manufacturing, addressing the need for greener, more efficient production methods that align with EU sustainability goals. One of the key aspects of this project is to explore enzyme promiscuity in the context of photochemical activation. Enzyme promiscuity refers to the ability of enzymes to catalyze reactions beyond their natural substrate range. By using light to activate these enzymes, we aim to unlock new reactivity that is not typically accessible under standard biological conditions. This approach not only expands the scope of enzyme-catalyzed transformations but also provides a means to discover new synthetic pathways that are more selective and environmentally benign.The project builds on the promising activity observed in enzymes such as FAP, which naturally catalyzes decarboxylation reactions under light activation. We have been able to develop radical addition reactions with FAP and LMO, which are valuable in creating carbon-carbon bonds, a critical step in many chemical syntheses. The integration of photobiocatalysis into synthetic chemistry represents a significant advancement over conventional chemical methods. Traditional chemical synthesis often requires high temperatures, extreme pH, and toxic reagents, which contribute to environmental pollution and increased energy consumption. In contrast, light-activated enzymatic processes occur under mild conditions, reducing both the energy requirements and the environmental footprint of chemical production. This aligns well with the EU's commitment to sustainable industrial processes and the development of green technologies. The impact of this project extends beyond the laboratory, as it aims to contribute to the development of sustainable manufacturing processes. By demonstrating the feasibility of using light-activated enzymes for complex chemical syntheses, we hope to encourage the adoption of biocatalysis in the pharmaceutical and chemical industries. This would not only reduce the reliance on traditional, energy-intensive chemical processes but also provide a pathway for the production of high-value compounds in a more sustainable and cost-effective manner.

Data: CORDIS, © European Union

Project 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.

Original text from CORDIS.

Participants

  • COMMISSARIAT A L ENERGIE ATOMIQUE ET AUX ENERGIES ALTERNATIVES · ParisCoordinatorFrance
  • TRUSTEES OF PRINCETON UNIVERSITY · Princeton, NjUnited States

Links

Data: CORDIS, © European Union