SURF - Synthetic Units for Redirecting Functionalities

Life’s success story on earth is largely based on the rewiring of a rather limited set of naturally occurring protein modules. We systematically analyzed the structural evolution of certain protein families by a computational approach, and deduced design principles for the creation of artificial scaffolds and catalysts with individualized properties. By this approach, we enable exchangeable and extendable protein libraries that carry synergistic functionalities. Our conceptual approach is challenged by the creation of chimeric proteins and their functional assessment as relevant biotechnological and biomedical applications for the sake of humankind.

To fulfill our mission we chose the following projects:

SilverSURF: Flagellin diversity as hub for synthetic scaffolds

Figure 1: Monomeric D2-Cup1-flagellin.
Spheres represent cupper ions

Environmental pollution with harmful quantities of heavy metal ions has become an urgent problem in these times. SilverSURF makes use of the flagellar filament that represents one of the largest scaffolds in nature, and combines it with the unique potential of high-affinity metal-binding domains. Specifically, we rationally designed synthetic flagellar filaments able to bind huge quantities of the metal ion silver and copper.

Figure 2: DARpin tetramer

Lung cancer is one of the most malignant cancers with poor prognosis. Next to the common therapies like surgery, radiation therapy and chemotherapy, antibody therapy is more specific. CancerSURF combines the scaffold of a tetrameric Streptavidin to increase the specificity of a DARPin to detect a prominent tumor marker of lung cancer cells, called EpCAM (epithelial cell adhesion molecule). This system can find several approaches in medical treatment, for example serving as an inhaled alternative to (aerosolized) chemotherapy or as a diagnostic tool via surgery, indicating remaining tumor cells.

Figure 3: tRNA bound to Arc1p-C-domain with its CCA-terminus pointed directly towards the active center of PheA.

Ribosomes synthesize proteins from amino acids using mRNA as blueprint and tRNAs delivering amino acids. However, the natural ability of ribosomes is limited to 20 L-amino acids. Non-ribosomal peptide synthetases (NRPSs) synthesize only small peptides, however, from a large number of natural and non-proteinogenic amino acids. RiboSURF aims at combining the huge repertoire of NRPSs with ribosomal protein synthesis to extend the synthetic scope of the ribosome. Specifically; we designed and probed the potential of synthetic catalysts that allow the aminoacetylation of tRNAs with non-proteinogenic amino acids.