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Artificial Lanthanide Enzymes for Selective Photocatalysis: 'Enlightening' Metalloenzyme Design and Evolution

Objective

Enzymes are efficient and selective biocatalysts. They are in high demand in chemical and pharmaceutical industry, as they facilitate more sustainable production processes. However, it remains challenging to develop novel enzymes that catalyze reactions beyond nature's synthetic repertoire. To tackle this problem, I propose a fundamentally new approach that merges metal-dependent chemical photocatalysis with enzyme engineering. Photoexcitation is a powerful catalytic tool. It enables alternative modes of substrate activation by generating radical intermediates. Controlling these reactive species to confer regio- and stereoselectivity, however, is a major challenge in synthetic chemistry. The key idea of this proposal is thus to perform photocatalytic reactions inside the chiral environment of artificial metalloproteins, which can be optimized efficiently by directed evolution. My group recently established the formation of lanthanide-protein complexes from highly stable, computationally designed protein scaffolds. Based on this work, we now aim to engineer a photoenzymatic platform for synthetically valuable chemistry. The main goal is to implement and optimize lanthanide photocatalysis in these proteins to facilitate stereoselective C-H activation and C-C bond forming reactions. Moreover, a fundamental mechanistic understanding how such new photocatalytic function emerges in proteins will be crucial for enzyme engineering. To that end, I propose a strategy that mimics natural evolution in a two-step process. Starting from libraries of naive small proteins, a high-throughput screen will first identify lanthanide binders, which are then exposed to a selection system that couples the survival of a bacterial host to an enzymatic detoxification reaction. PhotoLanZyme will yield a new class of sustainable and stereoselective photobiocatalysts. The approach is transferable to other photoredox-active metals, emphasizing its broad potential for synthetic applications.

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Topic(s)

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Funding Scheme

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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.

(opens in new window) ERC-2021-STG

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Host institution

TECHNISCHE UNIVERSITAET MUENCHEN
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.

€ 1 500 000,00
Address
Arcisstrasse 21
80333 Muenchen
Germany

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Region
Bayern Oberbayern München, Kreisfreie Stadt
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.

€ 1 500 000,00

Beneficiaries (1)

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