Details of Group leader - Prof Nick Turner
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Post: Professor, School of Chemistry Phone: +44 (0)161 306 5173 Email: Nicholas.turner@manchester.ac.uk Website: Click Me |
Research Biocatalysis, directed evolution of enzymes, chemical genetics. |
Current Research
Biocatalysis
We have been interested for some time in the application of enzymes and whole cell biocatalysts in organic synthesis, particularly for the preparation of optically active chiral intermediates. Attention has been focussed on the use of lipases, nitrilases, asymmetric C-C bond formation, asymmetric C-C bond cleavage, oxidation using P450 monooxygenases, glycosylransferases, nitroreductases and amino acid/amine/alcohol oxidases. Using the latter enzymes we have recently developed protocols for the deracemisation of racemates using an enantioselective enzyme (oxidase) in combination with a non-selective chemical reducing agent. We have also employed directed evolution/high-throughput screening strategies to identify amine oxidases with improved catalytic activity and enantioselectivity towards target substrates of interest. Further work is currently underway applying directed evolution to other enzymes including P450 mono-oxygenases, alcohol oxidases and amino acid oxidases. The overall focus of the biocatalysis work is the discovery of efficient routes for the selective synthesis of chiral intermediates intermediates for pharmaceuticals/agrochemicals.
Chemical Genetics
In collaboration with Professor Malcolm Walkinshaw, Institute of Cell and Molecular Biology at Edinburgh, we are engaged in a program of research whose aim is to discover novel therapeutic drugs to treat a range of diseases. We have also developed some novel high affinity ligands for cyclophilin which is the receptor for the immunosuppressant cyclosporin. Cyclophilin is an important target for novel anti-viral and anti-inflammatory therapies. Recently we have begun to look at anti-parasitic enzymes involved in glycolysis and also anticancer proteins involved in cell cycling processes. All of the projects involve an interplay of several disciplines including combinatorial and parallel synthesis, protein structure-based design, X-ray crystallography, mass spectrometry and new strategies for high-throughput screening of combinatorial libraries.
Service & Awards
- Director of Centre of Excellence in Biocatalysis, Biotransformation and Biocatalytic Manufacture (CoEBio3: www.coebio3.manchester.ac.uk)
- 1992 RSC Carbohydrate Medal
- 1995 Pfizer Academic Award
- 1996 RSC Corday-Morgan Medal
- 2004 Biocat Award
Funding
AstraZeneca - Avecia - BASF - BBSRC - Contract Chemicals - Dowpharma - DTI - EPSRC - Excelsyn - GlaxoSmithKline - Ingenza - MRC - Novacta
Recent Publications
- C.J. Dunsmore, R. Carr, T. Fleming and N.J. Turner, A Chemo-Enzymatic Route to Enantiomerically Pure Cyclic Tertiary Amines, J. Am. Chem. Soc., 128, 2224-2225, 2006.
- M. Wear, A. Patterson, K. Malone, C. Dunsmore, N.J. Turner and M.D. Walkinshaw, A Surface Plasmon Resonance-Based Assay for Small Molecule Inhibitors of Human Cyclophilin A, Anal. Biochem., 345, 214-226, 2005.
- Celik, D. Sperandio, R.E. Speight and N.J. Turner,, Identification of Broad Specificity P450CAM Variants by Primary Screening Against Indole as Substrate., Chem. Commun., , 3652-3654, 2005.
- Celik, S.L. Flitsch and N.J. Turner, Efficient Terpene Hydroxylation Catalysts Based Upon P450 Enzymes Derived from Actinomycetes, Org. Biomol. Chem., 3, 2930-2934, 2005.
- Celik, D. Sperandio, R.E. Speight and N.J. Turner, Enantioselective Epoxidation of Linolenic Acid Catalysed by Cytochrome P450BM3 from Bacillus megaterium., Org. Biomol. Chem., 3, 2688-2690, 2005.
- D.J.B. Hunter, G.A. Roberts, T.W.B. Ost, J.H. White, S. Mueller, N.J. Turner, S.L. Flitsch and S.K. Chapman, Analysis of the Domain Properties of the Novel Cytochrome P450 RhF., FEBS Lett., 579, 2215-2220, 2005.