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Conformational determinants of enzymatic per- and polyfluoroalkyl activation and selectivity

Objective

Per- and polyfluoroalkyl substances (PFAS) are persistent and pervasive environmental contaminants. Long-chain PFAS bioaccumulate in plants, humans, and wildlife, amplifying their toxicity and health risks, leading to increasing governmental regulations. Shorter-chain PFAS are being phased in by industry to replace longer-chain PFAS, but their toxicity is less known and they are harder to detect, highlighting the need for increased monitoring. The overall situation calls for rapid, accessible, and on-site methods to detect, differentiate, and break down diverse chain-length PFAS.

To address this challenge, I propose to investigate ‘fluoro-selectivity’: the capacity of enzymes to differentiate between PFAS of varying chain-lengths and fluorinated versus non-fluorinated compounds. Strikingly, fluoro-selectivity already occurs in enzymes in nature. Here, I propose to use a combination of bioluminescence and machine learning to decipher the fluoro-selectivity code of natural enzymes that undergo conformational changes in response to different PFAS. In tandem, I will establish a new method using a fluoro-selective resistance mechanism to discover environmental enzymes capable of breaking down fluorinated compounds. Finally, I will take advantage of the close structural similarity between firefly luciferases - the enzymes that enable fireflies to glow - and natural PFAS-activating enzymes known as acyl-CoA ligases. Leveraging this evolutionary relationship, I will construct fluoro-selective, bioluminescent enzymes to enable the design of real-time, in situ, and chain length-specific PFAS biosensors.

Mapping the first blueprint of enzymatic fluoro-selectivity will enable precision applications in environmental PFAS monitoring and remediation. More fundamentally, this work aims to reveal the underlying biochemical and evolutionary drivers of fluoro-selectivity from bacteria to fireflies, uncovering paths for the emergence of metabolic traits across the tree of life.

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Keywords

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Programme(s)

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Topic(s)

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2025-STG

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Host institution

EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Net EU contribution

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.

€ 419 327,00
Address
Raemistrasse 101
8092 Zuerich
Switzerland

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Region
Schweiz/Suisse/Svizzera Zürich Zürich
Activity type
Higher or Secondary Education Establishments
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Total cost

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.

€ 419 327,50

Beneficiaries (2)

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