Designing biocatalysts for non-natural carboligations

Building complex compounds such as fine chemicals and pharmaceuticals by linking carbon-carbon bonds is at the core of organic synthesis. However, current methods to construct carbon-carbon bonds often have significant shortcomings, such as the use of hazardous substances or the generation of toxic waste. Biocatalysis, the use of enzymes in organic synthesis, potentially offers a more eco-friendly and sustainable approach for carbon-carbon bond formation. However, many powerful transformations known in chemistry are not catalyzed by natural enzymes.The work described in the PhD thesis of Andreas Kunzendorf focuses on the discovery and engineering of new enzymes for several highly interesting carbon-carbon bond-forming reactions. The research yielded new biocatalysts for the synthesis of important cyclopropanes and efficient enzymes for the production of building blocks for pharmaceutically active γ-aminobutyric acids via extensive enzyme optimisation using directed evolution. The optimized enzyme variants could not only perform the reactions much faster but also provided the products with high selectivity. The results of this work are a stepping-stone towards more sustainable synthesis of pharmaceuticals and provide exciting opportunities to develop new enzymatic reactions not known in nature