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. Fields of science natural scienceschemical sciencescatalysisphotocatalysisnatural scienceschemical sciencescatalysisbiocatalysissocial scienceseconomics and businesseconomicssustainable economynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes Programme(s) HORIZON.1.1 - European Research Council (ERC) Main Programme Topic(s) ERC-2021-STG - ERC STARTING GRANTS Call for proposal ERC-2021-STG See other projects for this call Funding Scheme HORIZON-AG - HORIZON Action Grant Budget-Based Coordinator TECHNISCHE UNIVERSITAET MUENCHEN Net EU contribution € 1 500 000,00 Address Arcisstrasse 21 80333 Muenchen Germany See on map Region Bayern Oberbayern München, Kreisfreie Stadt Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00
