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Relieving Fe/αKG-dependent Halogenases from their Carrier-dependence

Project description

A genetic engineering approach to sustainable, more affordable enzymes

Unsustainable manufacturing processes make the chemical industry a major contributor to global pollution. Supported by the Marie Skłodowska-Curie Actions programme, the UNSHACKLED project will contribute to eco-friendly, enzyme-driven reactions that align with the European Green Deal. The research will focus on a heavily understudied class of enzymes that could create valuable chemical building blocks but are currently costly for factories because they rely on an expensive protein partner. Researchers will use molecular dynamics simulations and genetic engineering to study these proteins at a molecular level and redesign them to work completely independently. These modified enzymes will be tested in laboratory experiments. Project results could help create affordable, sustainable tools that unlock new chemical possibilities for industrial applications.

Objective

The chemical industry contributes majorly to environmental pollution due to unsustainable synthetic processes. Thus, green chemistry has been coined, defining principles to achieve environmental benign development.
Within the scope of this project we will pave the way for enzyme-catalyzed aliphatic halogenation. This approach will provide valuable building blocks to the chemical industry in compliance with the UN Sustainable Development Goals and the European Green Deal. We will focus our studies on iron/alpha-ketoglutarate-dependent halogenases (αKGH) which are a heavily understudied enzyme class. Especially, members that depend on an acyl-carrier protein, to deliver the substrate, are too costly for industrial implementation. While current research focuses on the discovery of carrier-free αKGHs, we will relieve carrier-dependent αKGHs from their protein partner. This will make those enzymes, and their vastly untapped substrate scope, more accessible to industrial application.
We will tackle this shortcoming through advanced enzyme design. The application of molecular dynamics simulation will generate insight about the interaction between acyl-carrier protein and αKGH. This will be used to expand the understanding of their relationship on a molecular level. The obtained findings will then provide the foundation for rational enzyme engineering to rid αKGHs from their carrier-dependence. In the following, rational design rules will be devised generally applicable to any carrier-dependent αKGH. Finally, in vitro experiments will be employed to validate our predictions, designing the first αKGH relieved from their carrier protein. By approaching this project I anticipate to expand my skill set with computational methods to guide rational enzyme design. The results of this project will not only provide a new understanding about the interaction between acyl-carrier protein and αKGHs but also make their valuable substrate scope accessible to industrial application.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

(opens in new window) HORIZON-MSCA-2025-PF

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Coordinator

UNIVERSITAT DE GIRONA
Net EU contribution
€ 194 074,56
Address
PLACA SANT DOMENEC 3
17004 Girona
Spain
Region
Este Cataluña Girona
Activity type
Higher or Secondary Education Establishments
Links
Total cost
No data

Partners (1)