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groningen biomolecular sciencesand biotechnology institute

biotransformation &biocatalysis

groningen biomolecular sciencesand biotechnology institutegroningen biomolecular sciencesand biotechnology institute

biotransformation &biocatalysisbiotransformation &biocatalysis

Information for guest researchers (3 mo- 1 year, fellowship holders or applicants)

Prof.dr. Dick B. Janssen

Biotransformation and Biocatalysis Group,

Groningen Biomolecular Sciences and Biotechnology Institute,

University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands

d.b.janssen@rug.nl

http://www.rug.nl/research/biotransformation-biocatalysis/research/

The group Biotransformation and Biocatalysis can accommodate guest researchers, Erasmus

exchange students (for 3-12 months) or PhD fellowship holders (4 years) for research and training,

the latter leading to a PhD at the University of Groningen. Guest will participate in the groups'

research program and receive training and supervision.

Research program

The research program is aimed at obtaining more insight in structure-function relationships

of enzymes, and at engineering enzyme variants with improved properties, such as higher

enantioselectivity or broader substrate spectrum. Discovery of new enzymes is done by genome

mining or by using metagenomic libraries. New enzymes are expressed in recombinant form and

characterized with respect to kinetic properties and applicability for biocatalysis or

biotransformation of xenobiotic compounds. Structural analysis and computational methods are

used to obtain insight in structure-function relationships, and to guide protein engineering aimed at

improving properties.

Current topics/projects

1. Discovery and engineering of ammonia lyases and aminotransferases. The work is aimed at

modifying the biocatalytic properties for new industrially relevant conversions, by protein

engineering. This includes increasing stability and modifying the substrate range by

computation-supported library and mutant design. New enzymes are discovered by genomic

approaches, using bioinformatics and homology modeling.

2. Integrating computational approaches in directed evolution. Using molecular modeling and

different computational methods (Rosetta, FoldX) we explore the possibilities to improve the

catalytic properties of enzymes for synthetic applications. Targets are: enhanced stability,

increased enantioselectivity, higher catalytic activity with difficult substrates, and increased

synthesis/hydrolysis ratios of enzymes that can be used in synthetic applications, such as

protease and penicillin acylase.

3. Enzyme discovery for synthetic biology. Artificial biosynthetic pathways have the potential of

replacing multi-step chemical synthesis of useful compounds, such as polymer precursors or

pharmaceutical ingredients. We use genome mining and protein engineering to discover and

modify the selectivity of enzymes and tailor them for use in biosynthetic pathways.

4. Applied biocatalysis. Using enzymes discovered or improved in our laboratory, we aim to

discover new conversion of relevance for biocatalytic synthesis of useful compounds. This

includes semi-synthetic antibiotics, epoxide derivatives, amino acids, and peptides. The work

normally includes a lot of analytical organic chemistry, but also chemical synthesis, enzyme

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groningen biomolecular sciencesand biotechnology institute

biotransformation &biocatalysis

groningen biomolecular sciencesand biotechnology institutegroningen biomolecular sciencesand biotechnology institute

biotransformation &biocatalysisbiotransformation &biocatalysis

preparation and assays, and kinetic analysis of enzyme reactions. This work focuses on

transaminases, P450s, dehydrogenases and hydrolytic enzymes.

5. Dehalogenase discovery and engineering. Using molecular modelling, site-directed

mutagenesis, directed evolution, and high-throughput screening, we aim to obtain variants of

haloalkane dehalogenase and halohydrin dehalogenase with new catalytic properties or higher

catalytic rates. For example, we aim to modify nucleophile selectivity of halohydrin

dehalogenases by changing the nucleophile binding loop.

Training

PhD students follow a training program of GBB, University of Groningen, which includes

specialized masterclasses (e.g. Protein Engineering) and more general courses (Scientific Writing in

English, Dynamic Presentation). For a PhD degree, the research should lead to generally 4 scientific

papers, and a PhD thesis, all in English.

There are biweekly meetings about the progress of the work with the group leader and lab

supervisor. There are also weekly research group meetings and department lectures, and there may

be classes or lecture series that can be followed.

Requirements

Completing a PhD in our group requires a completed MsC degree in Biochemistry,

Biotechnology, Chemistry, Biology or similar. A typical PhD requires 4 years of research work and

will focus on an independent research project within the research program of the group

(biotransformation, biocatalysis, enzyme discovery and engineering). A good command of English

is necessary.

The required practical background is hands-on experience with at least two of the following:

1. plasmid isolation, restriction digestion of DNA, PCR, and analysis of DNA samples by gel

electrophoresis and sequence analysis by bioinformatics tools

2. protein isolation, protein assays, enzyme assays using a spectrophotometer, calculation of

activities and steady-state kinetic parameters with Excel, Sigmaplot or similar, data analysis

with simulation and fitting software

3. experience in computational methods, such as homology modeling, protein crystallography,

docking and molecular dynamics simulations, protein analysis and design software, etc.

4. experience with synthetic and analytical organic chemistry, including HPLC, GC, and NMR.

This would qualify for projects in applied biocatalysis.

Support and expenses

Note that the group cannot provide financial support for the stay in the Netherlands or travel

to guest researchers or foreign PhD students. We can provide lab space and materials. Further

support must be obtained, if required, from the EU (Erasmus program or similar, check at your

university), another program, or from your home university or government agencies.

Applications

Please send a letter or e-mail to the address given on top and clearly explain your relevant

experience/ knowledge, as listed above under requirements, when requesting a stay in our

laboratory. Also specify your interest in the topics and techniques mentioned above. Enclose a CV,

a clear overview of your previous training, and names with contact details of 2-3 references (or

reference letters). Explain how your stay will be financed and if you need a visa.