Phd on topic: Oxidative C-H activation for C-C bond formation using flavin dependent enzymes


Research interest and scientific background: The Biocatalytic Synthesis group at the University of Graz aims to employ enzymes for organic synthesis to cut short long tedious synthetic routes. We develop new biocatalytic methods for synthesis, investigate reaction mechanisms and combine biocatalyst in cascade reactions (1-2).


Affiliation: The student will work at the Institute of Chemistry in the Biocatalytic Synthesis group at the University of Graz under the supervision of Wolfgang Kroutil. Cooperation is intended with Peter Macheroux, Karl Gruber and Anton Glieder. This project is directly connected to the doc.funds CATALOX.

Hypothesis and objective: The project aims to investigate the substrate promiscuity of a flavo-protein from an alkaloid pathway. This includes on the one hand to identify which functional groups in the substrate are required for activity (What is the minimum substrate?) and on the other hand which additional substituents in which positions of the substrate are tolerated. Furthermore, the kinetic of the reactions will be investigated. The approach also includes to establish efficient synthetic route for preparation of the substrates. This may include chemical as well as further biocatalytic steps.

Experimental approaches: Techniques required are standard organic synthesis as well as biocatalytic synthesis, cloning, protein expression in different host organisms, protein purification, reaction kinetics, enzyme activity and inhibitor assays.

The student will strongly interact with other research groups of the doc.funds Molecular Metabolism, the doc.funds CATALOX, the Austrian Centre of Industrial Biotechnology (acib) and the research and training network NAWI Graz and BioTechMed Graz.

References:

  1. Artificial Biocatalytic Linear Cascades for Preparation of Organic Molecules, J. H. Schrittwieser, S. Velikogne, M. Hall, W. Kroutil, Chem. Rev. 118, 270-348 (2018).
  2. Asymmetric Synthesis of (R)-1-Alkyl-Substituted Tetrahydro-ßcarbolines Catalyzed by Strictosidine Synthases, D. Pressnitz, E.-M. Fischereder, J. Pletz, C. Kofler, L. Hammerer, K. Hiebler, H. Lechner, N. Richter, E. Eger, W. Kroutil, Angew. Chem. Int. Ed. 57, 10683-10687 (2018).