The DFG has granted a Reinhart Koselleck project to Bernhard Hauer, Department of Technical Biochemistry. These projects enable outstanding researchers to pursue exceptionally innovative and higher risk projects.
In the last decades methods have been established to modify enzymes – nature’s catalysts – to be more and more suitable for very efficient and selective chemical synthesis. Commonly only the alteration of amino acid residues is a tool used in biotechnology. A closer look in the natural evolution of enzymes reveals insertion and deletions (InDels) as foundation for major rearrangement in protein structure resulting in enzymes with novel properties. Strategies based on these InDel mutations are still challenging as they often result in unstable proteins.
Mimicking nature in achieving high impact enzyme variants, the project will evaluate these InDels as an enzyme engineering strategy. The targets are highly flexible loops forming tunnels in the periphery of the active site of Rieske non-heme iron dioxygenases. This enzyme family catalyzes the incorporation of molecular oxygen to olefins and aromatics. We aim on expanding the substrate as well as the reaction scope resulting in highly sought after building blocks for pharmaceuticals and fine chemicals. Accompanied by crystal structures analysis as well as molecular dynamic simulations the project will help to gain deeper insight into how new functions can be implemented in enzymes.