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Project 8 Dr. Robin Teufel

Investigation of novel non-canonical flavoenzymes

Flavoenzymes catalyze a huge array of chemically demanding reactions in primary and secondary metabolism. The project aims to biochemically and structurally characterize recently discovered non-canonical flavoenzymes, such as the internal flavin oxygenase EpnF from eponemycin biosynthesis. Eponemycin and related compounds are produced by Actinobacteria (Streptomyces sp. Goodfellowiella sp.) and function as highly potent inhibitors of the proteasome β-subunit through their α,β-epoxyketone warhead, which inspired the development of the synthetic analogue carfilzomib approved for the treatment of multiple myeloma.  In eponemycin biosynthesis, EpnF catalyzes an unprecedented series of reactions, namely the successive decarboxylation, dehydrogenation and epoxidation of an α-dimethyl-β keto acid precursor into the α,β-epoxyketone pharmacophore. To date, the mechanism und structure of this key enzyme from eponemycin biosynthesis have not been elucidated.

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Contact

Dr. Robin Teufel

Emmy Noether Research Group Leader

Center for Biological Systems Analysis (ZBSA)

University of Freiburg

Habsburgerstr. 49, 79104 Freiburg, Germany

E-mail: robin.teufel@zbsa.uni-freiburg.de

Tel.: +49 (0) 761 203-97199

https://www.zbsa.uni-freiburg.de/projects/ag-teufel/Research

 

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