Phd on topic: Deracemization strategy for the production of chiral sulfoxides


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 Silvia Glueck. This project is directly connected to the doc.funds CATALOX.

Hypothesis and objective: The project aims to establish a biocatalytic strategy for the production of optically pure sulfoxides via a reduction-oxidation sequence starting from a racemate. The use of highly selective enzymes for the reduction followed by a chemo- and/or enzymatic oxidation step will lead after several cycles to the desired non-racemic products. Evaluation of biocatalytic parameters (substrate scope etc.), engineering of biocatalyst, evaluation of (bio)oxidation methods as well as optimization of the overall redox-sequence will be the focus of the project.

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

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

References:

  1. 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).
  2. Regioselective para-Carboxylation of Catechols with a Prenylated Flavin Dependent Decarboxylase, S. E. Payer, S. A. Marshall, N. Bärland, X. Sheng, T. Reiter, A. Dordic, G. Steinkellner, C. Wuensch, S. Kaltwasser, K. Fisher, S. E. J. Rigby, P. Macheroux, J. Vonck, K. Gruber, K. Faber, F. Himo, D. Leys, T. Pavkov-Keller, S. M. Glueck, Angew. Chem. Int. Ed. 56, 13893-13897 (2017).