Engineering Lanthanide-Dependent Artificial Metalloenzymes

Prof. Dr. Cathleen Zeymer, Department of Chemistry, Technical University of Munich (TUM), German, cathleen.zeymer@tum.de

The chemical and pharmaceutical industry is under increasing pressure to replace traditional chemical catalysis with sustainable biocatalytic approaches. However, it remains a major challenge to develop novel enzymes for chemical reactions beyond nature’s synthetic repertoire. A promising strategy is the design of artificial metalloenzymes, which combine the catalytic properties of an abiotic metal cofactor with the chiral environment of a protein scaffold that provides stereoselectivity. These systems are genetically encodable and therefore amenable to optimization by directed evolution, a technique mimics natural selection in the laboratory. We recently established the formation of specific metal-protein complexes from highly stable, computationally designed protein scaffolds. The metal ions are incorporated by dative anchoring, which exploits direct coordination by natural amino acids of the protein. We now work on turning these de novo metalloproteins into a biocatalytic platform for synthetically valuable reactions, including stereoselective carbon-carbon bond formations. Specifically, we developed a de novo TIM barrel scaffold with femtomolar affinity for lanthanides, where metal binding can be observed by sensitizing the element-specific luminescence. Lanthanide ions are not only potent Lewis acid catalysts; they also promote photoredox chemistry. Our ongoing work thus focuses on the development of artificial lanthanide enzymes.

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https://univienna.zoom.us/j/6295015321?pwd=U29LMFdNd25wODJNaGE0RDlQOE1zUT09

Meeting-ID: 629 501 5321

Kenncode: Ygf5s2