Phd on topic: Oxidation-reduction driven, multi-step transformations in sugar metabolism and synthesis: mechanism and application



Research interest and scientific background: Our research is at the interface of mechanistic enzymology and biocatalytic synthesis. We have a long standing interest in enzymes that are useful for production of bio-active glycosides. Here, we study enzymes that use oxidation of sugar substrates to promote further reactions via elimination chemistry. Dehydration to create deoxy-sugars and glycoside bond cleavage are important examples. We would like to have better understanding of the enzyme mechanisms and aim at the development of practical bio-transformations with these enzymes.

Affiliation: The student will work at the Institute of Biotechnology and Biochemical Engineering of Graz University of Technology under the supervision of Bernd Nidetzky. Cooperation partners in this project are from structural biology and computational enzymology. This project will be directly funded by CATALOX.

Hypothesis and objective: Eliminations linked to oxidation and reduction are important in sugar metabolism, but are not well understood mechanistically (see the Scheme). Using advanced tools of enzymology, including computational methods, we will investigate recently discovered enzymes that promote cleavage of natural product glycosides and dehydration of sugars.

Experimental approaches: Besides classical methods of protein chemistry and enzymology, we will use synthetic substrates and substrate analogues to probe enzymatic mechanisms. Determination of relevant protein structures complements the experimental study. Enzymatic reactions are analyzed by computational methods.

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

References:

  1. Pfeiffer, M., Johansson, C., Krojer, T., Kavanagh, K. L., Oppermann, U., Nidetzky, B. (2019) A parsimonious mechanism of sugar dehydration by human GDP-Mannose 4,6-dehydratase. ACS Catal. 9, 2662-2668.
  2. Eixelsberger, T., Horvat, D., Gutmann, A., Weber, H., Nidetzky, B. (2017) Isotope probing of the UDP-apiose/UDP-xylose reaction: evidence of a mechanism via coupled oxidation and aldol cleavage. Angew. Chemie Int. Ed. Engl. 56, 2503-2507.