Mr. Thomas Classen
Institute of Bioorganic Chemistry
Research Center Jülich GmbH
Stetternicher Forst, Building 15.8 Room 212
52426 Jülich, Germany
Mini Academic CV
University degrees:First degree or intermediate examination:
- Bachelor of Science (Biochemistry), 2007, Heinrich-Heine-University Düsseldorf, Germany
- Master of Science (Biochemistry), 2009, Heinrich-Heine-University Düsseldorf, Germany
BioStruct PhD projectStructure Based Design of Aldolases
Pyruvate dependent aldolases catalyze the aldol reaction between pyruvate or phosphoenolpyruvate and an acceptor molecule. The reaction type is difficult to realize with conventional synthetic methods especially when control of stereoselectivity is required. In contrast to this, enzymes catalyze the transformation allowing mild reaction conditions (ambient temperature and pressure) and do often have high stereo-, regio- and chemoselectivity. However, there are still several challenges when using enzymes in preparative scale:
- Non-natural substrates are often not acceptable and might even inhibit the enzyme.
- The reaction partner (the carbonyl component) should sterically not be demanding.
- The selectivity should be high; however, both enantiomeric products should be accessible via the biocatalytic approach.
- The process should be scalable.
- A high throughput screening assay (activity and selectivity) is currently established.
- The wild-type enzyme is currently produced to verify the assay.
- As a starting point for the PhD project, (in silico) docking experiments (Gohlke) based on the X-ray structure should allow suggesting sites for mutagenesis.
- The designed library will be evaluated with the assay; it will be attempted to crystallize the new catalysts (Groth) thus generating a sound basis for further rounds of evolution and underpinning the in silico data.
- Best 'hits' will be evaluated for transformations in preparative scale.
Complementary Supervisor: Prof. Dr.Georg Groth, Institute for Plant Biochemistry, Heinrich Heine University Duesseldorf, Groth Group
Complementary Supervisor: Prof. Holger Gohlke, Institute of Pharmaceutical and Medicinal Chemistry, Heinrich Heine University Duesseldorf, Gohlke Group
BioStruct Fellow: Mr. Thomas Classen
Last updated: 22.11.2012, 14:21