Phd on topic: Enzymatic reductive cyclizations with ene reductases as biocatalysts

Research interest and scientific background: The Breinbauer group is interested in the development of new synthetic methods expanding the tool box of organic synthesis, and in a chemical biology approach validating enzymes as drug targets by designing inhibitors and investigating biosynthetic mechanisms. In general these investigations are driven by a deep mechanistic understanding of the underlying reactions.

Affiliation: The student will work at the Institute of Organic Chemistry at the Graz University of Technology. This project is directly connected to the doc.funds CATALOX.

Hypothesis and objective: Flavin-dependent ene reductases from the Old-Yellow-Enzyme (OYE) catalyze the stereospecific reduction of activated C=C double bonds. We could recently show that reengineered variants of ene reductases can perform the reductive formation of C-C bonds yielding cyclopropanes in high enantiomeric excess.(1) In collaboration with Karl Gruber and Peter Macheroux, the project aims at creating reductive C-C-cyclases using a rational design approach and extending the scope of this transformation to substrates leading to 4- and 5-membered ring structures.

Experimental approaches: The techniques required are standard organic synthesis as well as biocatalytic synthesis, cloning, protein expression and protein purification. The project will be complemented by the doc-funds project in the Gruber lab, which uses a bioinformatics and structural biology approach in developing new reductive cyclases.

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


  1. K. Heckenbichler, A. Schweiger, L. A. Brandner, A. Binter, M. Toplak, P. Macheroux, K. Gruber, R. Breinbauer, Asymmetric reductive carbocyclization using engineered ene reductases, Angew. Chem. Int. Ed., 57 (2018), 7240-7244.