Objective
Enzymes have been classically investigated as standalone catalysts operating in a relatively diluted milieu. However, the cell micro-compartments are highly crowded environments and biological catalysis cannot be fully understood on the bases of simple diffusive models. We are tackling this challenge by reconstituting a full-scale biosynthetic pathway where multiple enzymes coordinate within a metabolon - a structurally defined setting that allows the vectorial transfer of substrates and products.
Our system for exploration is the fascinating biosynthesis of coenzyme Q, an essential redox mediator for many pathways. The juxtaposition between its highly polar head group and hydrophobic tail renders this compound a challenging feat to handle. To synthesise its highly substituted aromatic head group, nature has amassed a large soluble supra-molecular complex consisting of no less than eight functionally distinct proteins that adheres to the inner-mitochondrial membrane. This infrastructure can extract the substrate whilst providing a shielded, hydrophobic environment for molecular transit.
We will systematically characterize the functional, structural and evolutionary aspects of the involved protein machineries in interplay with the membrane. Our approach starts by exploiting ancestral sequence reconstruction to generate proteins of enhanced stability. We will build the metabolon in vitro to assess how the enzymatic activities are coupled in the context of a metabolon. Structural studies will reveal how the active sites are spatially organized with respect to the order of the enzymatic steps and substrate trafficking. Our integrated strategy will unveil the pivotal evolutionary transitions that create a biosynthetic machinery. This research will go beyond classical enzymology by exploring a new paradigm of cellular biochemistry where metabolic pathways are fuelled and governed through interactions between enzymes, and between enzymes and other proteins.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- natural sciences chemical sciences catalysis
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
MAIN PROGRAMME
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Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-ERC - HORIZON ERC Grants
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2022-ADG
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
27100 Pavia
Italy
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.