Project description
Engineering enzymes for sustainable synthesis of axially chiral drug molecules
Controlling a molecule’s three-dimensional shape is essential for its physical and biological properties. Atropisomers, which possess axial chirality due to hindered bond rotation, influence pharmacological outcomes. However, their selective synthesis remains a challenge in drug development. Current methods often rely on inefficient chromatographic separations. Supported by the Marie Skłodowska-Curie Actions Programme, the AtropEnzymes project will engineer enzymes for novel, atroposelective C–N bond-forming reactions. Using directed evolution, machine learning and computational design, this research aims to establish a sustainable biocatalytic framework for the efficient production of medicinally relevant, axially chiral compounds.
Objective
The control of a molecule’s three-dimensional shape has important implications for both its physical and biological properties. Atropisomers—stereoisomers resulting from hindered rotation around a single bond—exhibit axial chirality that can profoundly impact pharmacological properties, making their selective synthesis increasingly important in drug development. Although the number of single-atropisomer pharmaceuticals has significantly grown over the past decade, methods for their stereoselective preparation remain limited, with inefficient and costly chromatographic separations still widely used. This project addresses this challenge by engineering enzymes capable of novel atroposelective C–N bond-forming reactions, providing direct access to medicinally relevant axially chiral scaffolds. The approach will combine enzymatic desymmetrisation to access electron-rich biaryl atropisomers with atroposelective SNAr reactions to generate electron-poor counterparts. Directed evolution will be applied to enhance activity and selectivity, supported by machine learning to accelerate optimisation and computational protein design to improve enzyme function. Together, these studies will establish a biocatalytic platform for the efficient, sustainable synthesis of drug-like atropisomeric compounds.
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: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs
- 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.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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-TMA-MSCA-PF-GF - HORIZON TMA MSCA Postdoctoral Fellowships - Global Fellowships
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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) HORIZON-MSCA-2025-PF
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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.
M13 9PL Manchester
United Kingdom
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.