Project description
Leveraging enzymes to improve polyene antifungals
Polyenes are organic compounds containing multiple alternating single and double carbon-carbon bonds. They are powerful antifungal antibiotics for severe fungal infections, but they face numerous challenges. Current methods to address these are costly, environmentally unfriendly, multi-step processes with low yield. With the support of the Marie Skłodowska-Curie Actions programme, the CERIPA project aims to develop a combined chemical and enzymatic approach to modify polyenes, improving antifungal activity, safety and solubility. CERIPA will investigate different families of enzymes to both modify the polyene molecular backbone and to attach non-native sugar moieties at specific sites. Structure-activity relationships will shed light on the optimal enzymes and modifications, supporting the rational design of next-generation antifungal agents.
Objective
Fungal infections are an increasingly serious global health threat, driven by rising antimicrobial resistance (AMR) and a critical lack of new antifungal drugs in development. Currently, treatment relies heavily on Amphotericin B (AmB) and a small group of related polyene natural products. However, the clinical use of these compounds is limited by their poor solubility and significant toxicity. Research has shown that chemical modifications of polyenes like AmB can reduce their toxicity, but traditional synthetic approaches to producing these derivatives are far from ideal. These methods typically involve multiple, low-yielding steps, making them costly, environmentally unfriendly, and difficult to scale. Moreover, they often rely on heavy metals, hazardous reagents, and extensive use of protecting groups—practices that conflict with the principles of green chemistry, including step- and atom-economy. The CERIPA project aims to address these challenges by developing cleaner, more efficient, and sustainable chemoenzymatic approaches to modifying polyenes. Our goal is to generate new derivatives with enhanced antifungal activity, reduced toxicity, and improved solubility. We plan to diversify polyene structures by using a newly discovered family of glycosyltransferases to attach non-native sugar moieties at specific sites. Additionally, we will explore the use of other polyene-modifying enzymes to further tailor the molecular backbone. These newly engineered polyene analogues will undergo rigorous bioactivity and toxicity testing to establish structure–activity relationships (SARs), guiding the rational design of next-generation antifungal agents.
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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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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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
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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-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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(opens in new window) HORIZON-MSCA-2025-PF
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SW7 2AZ London
United Kingdom
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