Phd on topic: Biocatalytic Reduction of Oximes


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 (1-3).

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

Hypothesis and objective: The project aims to investigate the reduction of oximes using known flavin dependent redox enzymes. Prestudies have already indicated that selected oximes can indeed be reduced via highly reactive intermediates. The applicability of the identified enzymes for the reduction of various oximes will be demonstrated. The requirements of compounds for trapping reactive intermediates will be elucidated as well as the identification of generated products. Reactive species may be produced in a cascade. Preferences for E or Z oximes will be elucidated.

Experimental approaches: Techniques required are standard organic synthesis as well as biocatalytic synthesis, cloning, protein expression, protein purification, reaction kinetics, enzyme activity, all kinds of analytics (GC, HPLC, MS, NMR etc).

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-ß-carbolines 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).
  3. Multienzyme One-Pot Cascade for the Stereoselecitve Hydroxyethyl Functionalization of Substituted Phenols, S. E. Payer, H. Pollak, B. Schmidbauer, F. Hamm, F. Juricic, K. Faber, S. M. Glueck, Org. Lett. 20, 5139-5143 (2018).