Research Focus

The Group of Prof. Rita Bernhardt would like to understand mechanisms of enzyme-catalyzed reactions in order to regulate them in the event of illness or to make them usable for biotechnological application with the help of protein design. We deal in particular with the analysis of cytochrome P450 systems and their applications in biotechnology and medicine.

Cytochrome P450 systems catalyze the following reaction:
RH + O2 + NAD(P)H -------> ROH + H2O + NAD(P)+

The reactions catalyzed by them are very diverse and include, for example hydroxylations, N-, O- and S-dealkylations, sulfoxidationens, epoxidations, deaminations, desulfurization, dehalogenations, peroxidations, and N-oxide reductions. Their substrates are fatty acids, steroids, prostaglandins, but also a great number of other substances, such as drugs, anesthetics, organic solvents, ethanol, alkyl-aryl hydrocarbons, pesticides and carcinogens.
It is obvious that this number of substrates and catalyzed reactions can not be implemented by a few isoforms of cytochrome P450: So far, more than 18 000 P450 genes from different organisms have been identified.
The diversity of the cytochromes P450 and the reactions they catalyze have attracted the interest of researchers from very different directions. Pharmacologists and toxicologists as well as endocrinologists, physiologists, microbiologists, organic chemists, plant physiologists and ecologists work on various aspects of function and regulation of P450:

P450

Basic research projects

  • Characterization of the effects of metabolites and derivatives of the steroid metabolism on the steroid biosynthesis.

  • Analysis of the structural basis for the stereo-and regioselectivity of hydroxylation, especially of steroids, by cytochrome P450-dependent reactions.

  • Regulation of the speed of the cytochrome P450-dependent hydroxylation. How are electrons transferred from the electron-donor molecule to the steroid hydroxylases? What are the main characteristics of the involved redox chain (ferredoxins, reductases)? How functions the protein-protein interactions?

  • Functional and structural analysis (cloning, expression and characterization) of Cytochromes P450, ferredoxins and FAD-dependent reductases present in Sorangium cellulosum.

  • Elucidation of the structure and function of bacterial steroid and terpenoid hydroxylases from Bacillus megaterium.

  • Applied research projects

  • Optimization of cytochromes P450 for biotechnological synthesis through design and production of efficient biocatalysts.

  • Use of cytochromes P450 for selective steroid hydroxylations.

  • Analysis of the role and use of bacterial cytochromes P450 for the hydroxylation of terpenoids with possible applications in the biosynthesis of new compounds, flavors and fragrances.

  • Analysis of the effects of steroid hormones (eg aldosterone, cortisol) on the genesis of cardiac fibrosis, and the development of systems for the testing of potential inhibitors.

  • Molecular genetic characterization of steroid hydroxylases of patients with defects in the steroid biosynthesis.