Photodecarboxylases for Stereoselective C-C Bond Formations

Modern chemistry faces multiple challenges: creating synthetic methods that are not only efficient and flexiblebut also sustainable and highlyselective. The FWF-fundedresearch project Photodecarboxylases for Stereoselective CC Bond Formations addresses this challenge by combining the synthetic capabilities of photocatalysis to build up complex molecular structures, with the exceptional selectivity of enzymesnatures own catalysts. This project explores the unique class of enzymes known as photodecarboxylases. These light- dependent biocatalysts, which play a role in the lipid metabolism of photosynthetic bacteria, offer exciting opportunities for chemical synthesis. By studying the mechanisms of these enzymes in detail, the research team has developed novel enzyme variants capable of catalyzing a photobiocatalytic version of the Giese reactiona type of carboncarbon bond formation that has never before been observed in nature. The projects goal is to optimize and expand the capabilities of these enzymes using advanced enzyme engineering and directed evolution techniques. In doing so, the team will develop even more new-to- nature reactions that are highly stereo-, chemo-, and regioselective, paving the way for greener and more precise chemical transformations. An interdisciplinary team is key to this endeavor. Organic chemists and molecular biologists Christoph Winkler and Wolfgang Kroutil (University of Graz), in collaboration with structural biologist and computational chemist Marc Garcia-Borràs (University of Girona), are working together to bring this vision to life. The project will focus on the following main objectives: Developing novel photobiocatalytic coupling reactions with exceptional selectivity Creating a library of engineered photodecarboxylases through directed evolution, enabling a platform for future enzyme-mediated new-to-nature photoredox reactions Driving these innovations through mechanistic insights, combining experimental and computational studies of both natural and promiscuous enzyme-catalyzed reactions This research not only contributes to fundamental science but also holds promise for transforming how we approach chemical synthesis in a more sustainable and precise way.