Directed Evolution as a Means to Optimize and Understand Molecular Biocatalysts

• Applicant: Professor Dr. Manfred T. Reetz
• Subject Area: Biochemistry
• Term: from 2004 to 2011
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5427415

The purpose of this project is to apply the methods of directed evolution in the quest to create enantioselective epoxide hydrolases as catalysts in organic synthesis and to uncover the source of stereoselectivity on a molecular basis. Close collaboration with the biologist/toxicologist Prof. Dr. Michael Arand (Universität Würzburg, Germany) who has developed expression systems of the two epoxide hydrolases to be used (Aspergillus niger and limonene epoxide hydrolase) and the theoretician Prof. Dr. Walter Thiel in our own institute is an integral part of the project. Both have submitted applications in this DFG-Schwerpunkt. We plan to learn from directed evolution by performing appropriate cycles of mutagenesis/eescreening, structurally characterizing the most enantioselective mutants and carrying out theoretical studies using molecular dynamics and quantum mechanical calculations in order to uncover the source of enantioselectivity.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1170: Directed Evolution to Optimise and Understand Molecular Biocatalysts