Objective
In the past decade, artificial metalloenzymes (AMs) have emerged as an attractive alternative to the more traditional enzymes and homogeneous catalysts. Such hybrid catalysts result from the incorporation of an abiotic metal cofactor within a macromolecule (protein or oligonucleotide). Artificial metalloenzymes combine attractive features of both homogeneous catalysts and enzymes, including the possibility to genetically optimize the catalytic performance of new-to-nature organometallic reactions. Can artificial metalloenzymes become as catalytically efficient as naturally-evolved metalloenzymes, even in complex biological mixtures? Herein, we outline our efforts to address this challenge by localizing and evolving AMs within the periplasm of Escherichia coli.
To achieve this objective, we will exploit AMs based on the biotin-streptavidin technology. Four subprojects have been tailored to address the challenges: i) knock-out deleterious components present in the periplasm; ii) improve the cofactor uptake through the outer-membrane; iii) engineer streptavidin to boost the AM’s performance; and iv) rely both on screening and selection strategies to evolve AMs in vivo. Relying on auxotrophs, we will demonstrate the potential of AMs to complement metabolic pathways. Only E. coli auxotrophs containing an evolved AM capable of producing the vital aminoacid-precursor will survive the stringent selection pressure. We have identified several selectable aminoacid precursors which can be produced by metathesis (indole, precursor of tryptophan), enone reduction (keto valine, precursor of valine) and allylic substitution (prephenate, precursor of tyrosine and phenylalanine). In a Darwinian evolution spirit, we anticipate that applying selection pressure will allow to evolve AMs to unprecedented catalytic performance.
The main deliverable of the DrEAM is an engineered and evolvable E. coli strain capable of performing in vivo reaction cascades combining AMs and natural enzymes.
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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H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
MAIN PROGRAMME
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Topic(s)
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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.
ERC-ADG - Advanced Grant
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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-2015-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.
4051 Basel
Switzerland
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.