Phd on topic: Multistep biocatalytic cascade reactions in continuous flow


Research interest and scientific background: The activities of the research group of Heidrun Gruber-Woelfler include the (bio)catalytic synthesis of active pharmaceutical ingredients (APIs), continuous processes, reactor design including additive manufacturing (3D printing) as well as in-line analyses. A special focus lies on the development of heterogeneous (bio)catalysts and their implementation in continuous flow set-ups (1-4).

Affiliation: The student will work under the supervision of H. Gruber-Woelfler at the Institute of Process and Particle Engineering at the Graz University of Technology. This project is directly connected to the doc.fund CataLOX. Cooperation is intended with Robert Kourist and Bernd Nidetzky.

Hypothesis and objective: Reactions in continuous flow have several advantages, such as constant product quality, feasible automatization and real-time analyses as well as the ability to couple several steps without interruption. The aim of this project is to develop a process for multistep (bio)catalytic cascade reactions with immobilized enzymes (oxidoreductases) in continuous flow. The reactions can be carried out in the so-called “plug and play” reactor (2), which features exchangeable HPLC columns filled with the immobilized enzymes as reaction segments and modules for heating/cooling and mixing. Challenges include possible leaching of the enzymes, the precise addition of the co-substrates as well as the possible interaction of by-products within the following catalytic step.

Experimental approaches: The project involves techniques for enzyme (co)immobilization, catalytic cascades and the application of bio- and chemocatalysts in continuous flow. Prior knowledge in these areas as well as standard analytics (GC, HPLC, NMR) and reactions kinetics is helpful.

The student will strongly interact with other research groups in the area of continuous processes, the doc.fund CataLOX, the doc.fund Molecular Metabolism, as well as national and international training networks.

References:

  1. Lichtenegger, GJ, Maier, MC, Khinast, J & Gruber-Wölfler, H* 'Continuous Suzuki-Miyaura reactions with novel Ce-Sn-Pd oxides and integrated crystallization as continuous downstream protocol' J. Flow Chem. 2016, 6(3) 244 - 251
  2. Lichtenegger, GJ, Turšič, V, Kitzler, H, Obermaier, K, Khinast, J & Gruber-Wölfler, H*, 'The Plug & Play Reactor: A Highly Flexible Device for Heterogeneous Reactions in Continuous Flow' CIT 2016, 88 (10), 1518–1523
  3. Hiebler K., Lichtenegger G.J., Maier M.C., Park E.S., Gonzales-Groom R., Binks B.P.*, Gruber-Woelfler, H.* Heterogeneous Pd-catalysts as emulsifiers in Pickering emulsions for integrated multi-step synthesis in flow, Beilstein J. Org. Chem. 2018, 14, 648-658,
  4. Grabner B.*; Nazari M.; Gundersen M.T.; Lois S.; Fantini S.; Bartsch, S.; Woodley J.M.; Gruber-Woelfler H.*, “Room-Temperature Solid Phase Ionic Liquid (RTSPIL) Coated ω-Transaminases: Development and application in Organic Solvents”, Molecular Catalysis 2018, 452, 11-19