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Project 12 Prof. Michael Müller

Regio– and stereoselective oxidative phenol coupling catalyzed by P450 enzymes

The major aim of this project is the exploration of the diversity of P450-dependent enzymes involved in intermolecular phenol coupling in bacteria. For this, biochemical, structural and biocatalytic studies will be performed in vitro. The project will be supported by an additional line of work on fungal enzymes supported by external funding.

 Figure 1: Postulated biosynthesis of julichrome compounds.

In order to obtain an impression of the structure of the bacterial cytochrome P450 enzymes JulI, SetI and SptI, a preliminary protein homology model of each was generated. These and the additional docking experiments suggested that the active site provides sufficient space for monomers and the resultant dimers. The target enzymes will be heterologously produced in E. coli and their structure determined. Subsequently, essential residues will be determined by site-directed mutations and the model refined concerning regio- and stereoselectivity issues. Absolute configuration will be determined using chiroptical methods.

 

 

Contact

Prof. Dr. Michael Müller

Institute of Pharmaceutical Sciences

Pharmaceutical and Medicinal Chemistry

Albertstr. 25

79104 Freiburg

Phone: +49 (0) 761 203-6320

Fax: +49 (0) 761 203-6351

email: michael.mueller@pharmazie.uni-freiburg.de

http://portal.uni-freiburg.de/pharmazeutische-chemie/forschung/forschung-mueller

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