Rare Earth Lewis Acid Biocatalysis in Designer Enzymes

• Applicant: Dr. Kevin Schwitalla
• Subject Area: Biochemistry ; Inorganic Molecular Chemistry - Synthesis and Characterisation ; Organic Molecular Chemistry - Synthesis and Characterisation
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 572719335

The aim of this project is to develop rare earth designer enzymes that can perform biocatalytic, new-to-nature reactions inspired by the broad range of rare earth-catalyzed reactions at ambient conditions with high yields and enantiomeric excess. To achieve this, we will incorporate non-canonical amico acids with metal-binding sites into the Lactococcal multidrug resistance regulator enzyme scaffold at various positions and investigate the binding capabilities of rare earth Lewis acids. Using these rare earth designer enzymes, we will carry out rare earth-catalyzed reactions (e.g. Michael reactions, cycloadditions and multicomponent reactions) and evaluate the outcome of the reactions based on yield and enantiomeric excess. To realize the full potential of artificial enzymes and to maximize selectivity and activity, we will use directed evolution to optimize our designer enzymes for specific reactions. We will investigate the structure-activity relationships with single-crystal X-ray diffraction and computational modelling to understand the reasons behind of successful reactions and to develop a rational approach for the design of enzymes. Ultimately, our approach aims to achieve more sustainable and greener syntheses of pharmaceuticals and natural products, thereby advancing the field of biocatalysis.

• DFG Programme: WBP Fellowship
• International Connection: Netherlands
• Host: Professor Dr. Gerard Roelfes