Phd on topic: Novel biocatalysts for the hydroxylation of heterocyclic compounds


Research interest and scientific background: The Glieder group at the Graz University of Technology established crucial gene expression technologies for protein production and engineering of enzymes which are difficult to express and the balanced expression of such enzymes for whole cell catalyzed biosynthetic routes. (1-3).

Affiliation: The student will work at the Institute of Molecular Biotechnology at the Graz University of Technology. Cooperation is intended especially with Margit Winkler, Peter Macheroux, Bernd Nidetzky, Wolfgang Kroutil and international partners. This project is directly connected to the doc.funds CATALOX.

Hypothesis and objective: The project aims to investigate the hydroxylation of heterocyclic compounds using cytochrome P450 and related enzymes. Preliminary studies indicated the catalytic potential of soluble bacterial fusion enzymes to catalyze these reactions. A comparison to microbial enzymes using the peroxy-shunt pathway should identify potential advantages and disadvantages of such alternative to the classical P450 approaches.

Experimental approaches: Enzyme expression and engineering, biotransformations on small scale and analytics (GC, HPLC, MS, high throughput analysis 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), The “Christian Doppler Laboratory for Pichia pastoris Host and Vector Development” and the research and training network NAWI Graz and BioTechMed Graz.

References:

  1. Vogl T, Kickenweiz T, Pitzer J, Sturmberger L, Weninger A, Biggs BW, Koehler EM, Baumschlager A, Fischer J, Hyden P., Wagner M, Baumann M, Borth N, Geier M, Ajikumar PK, Glieder A. Engineered bidirectional promoters enable rapid multi-gene co-expression optimization. Nature Communications, volume 9, Article number: 3589 (2018)
  2. Migglautsch AK, Willim M, Schweda B, Glieder A, Breinbauer R, Winkler M, Aliphatic hydroxylation and epoxidation of capsaicin by Cytochrome P450 CYP505X. Tetrahedron 74 (2018) 6199e6204
  3. Winkler M, Geier M, Hanlon SP, Nidetzky B, Glieder A. Human Enzymes for Organic Synthesis. Angew Chem Int Ed Engl. 2018 Mar 30. doi: 10.1002/anie.201800678.