个人简介
1973 PhD Biophysics, Kings College, University of London
1969 MI Biology (by examination) Biochemistry, special topic Microbial Biochemistry
1967 LI Biology (by examination) Physical and Organic Chemistry, Biochemistry
Career
1999-present Professor of Biological Chemistry, University of Exeter & Director of Exeter Biocatalysis Centre
1991-1994 Senior Lectureship (Wellcome Trust) in Biological & Medicinal Chemistry, University of Exeter
1984-1991 SERC Senior Research Fellow, Biotechnology Directorate, University of Bristol
1981-1984 Principal Investigator, MRC Project Grant, Department of Biochemistry, University of Bristol
1975-1981 Group Leader, Max-Planck Instut fur Molekular Genetik, Berlin, Germany
1974-1975 Instructor, Department of Biochemical Sciences, Princeton University, USA
1974 Department of Biochemical Sciences, Princeton University, USA
1973 Department of Biophysics, Kings College, University of London
研究领域
Our work is multi-disciplinary in nature covering molecular genetics (site-directed mutagenesis and gene isolation and cloning), protein purification and characterisation, and structural analysis by NMR, X-ray crystallography and molecular modelling.
Biotransformations. Structural and mechanistic characterisation of the C-C bond forming enzymes transketolase and aldolase, vanadium haloperoxidases, Baeyer-Villiger monooxygenases, aminoacylases, novel esterases and lipases, gamma lactamases, alcohol dehydrogenases, nitrilases, transaminases, dehalogenases and other enzymes from thermophilic bacteria and archaea have been carried out. The results have provided information on the properties, substrate specificity and structure of these industrially important biocatalysts. This work has attracted industrial collaborations with a number of international companies and SME‘s including Chirotech/DowPharma, Stylacats, Affiniti/Biomol, TMO Biotech, Alphamerix, PML Corporation Ltd., Fluka/Sigma Aldrich, DSM, YorkPharma, Diversa and Glaxo-Smith Kline. I have co-ordinated a recent DTI Technology Transfer programme with AquaPharm, Oban to exploit marine enzymes. I am UK representative of the European Section on Applied Biocatalysis and an affiliated member of the CoE in Biocatalysis in Manchester.
Human enzymes and their importance in drug design. The structures of several human glycolytic enzymes have assumed special significance due to their potential use in drug design. My research has concentrated on phosphoglycerate kinase and aldolase and our studies have contributed to the determination, three dimensional structure and mechanism of these enzymes. Other human enzymes with medicinal interest have recently been studied such as human glucokinase (diabetes) and perioxiredoxin and sulfiredoxin (antioxidant proteins and their complexes with Peninsula Medical School) and pyroglutamyl carboxypeptidase (peptide N-terminal modification). I am collaborating with the Biophysics group at Exeter on the development of enzyme biosensors.
Other collaborations with Prof Brophy, Aberystwyth on the structural investigation of nematode specific GST proteins. Also structural studies on novel plant enzymes from the vitamin C pathway and involved in fungal infection with Exeter colleagues.
近期论文
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Zarafeta D, Kissas D, Sayer C, Gudbergsdottir SR, Ladoukakis E, Isupov MN, Chatziioannou A, Peng X, Littlechild JA, Skretas G, et al (2016). Discovery and Characterization of a Thermostable and Highly Halotolerant GH5 Cellulase from an Icelandic Hot Spring Isolate. PLoS One, 11(1). Abstract. Author URL. Full text. Article has an altmetric score of 1
sayer C, Finnigan W, Isupov MN, Levisson M, Kengen SWM, van der Oost J, Harmer NJ, Littlechild JA (2016). Structural and biochemical characterisation of Archaeoglobus fulgidus esterase reveals a bound CoA molecule in the vicinity of the active site. Scientific Reports, 6, 25542-25542. Abstract. Full text. Article has an altmetric score of 1
Littlechild JA (2015). Archaeal Enzymes and Applications in Industrial Biocatalysts. Archaea, 2015, 1-10. Full text. Article has an altmetric score of 1
Ferrandi EE, Sayer C, Isupov MN, Annovazzi C, Marchesi C, Iacobone G, Peng X, Bonch-Osmolovskaya E, Wohlgemuth R, Littlechild JA, et al (2015). Discovery and characterization of thermophilic limonene-1,2-epoxide hydrolases from hot spring metagenomic libraries. FEBS J, 282(15), 2879-2894. Abstract. Author URL. Article has an altmetric score of 1
Littlechild JA (2015). Enzymes from Extreme Environments and Their Industrial Applications. Front Bioeng Biotechnol, 3 Abstract. Author URL. Full text. Article has an altmetric score of 1
Sayer C, Isupov MN, Bonch-Osmolovskaya E, Littlechild JA (2015). Structural studies of a thermophilic esterase from a new Planctomycetes species, Thermogutta terrifontis. FEBS J, 282(15), 2846-2857. Abstract. Author URL. Article has an altmetric score of 1
Sayer C, Szabo Z, Isupov MN, Ingham C, Littlechild JA (2015). The Structure of a Novel Thermophilic Esterase from the Planctomycetes Species, Thermogutta terrifontis Reveals an Open Active Site Due to a Minimal 'Cap' Domain. Front Microbiol, 6 Abstract. Author URL. Full text. Article has an altmetric score of 1
Isupov MN, Schröder E, Gibson RP, Beecher J, Donadio G, Saneei V, Dcunha SA, McGhie EJ, Sayer C, Davenport CF, et al (2015). The oxygenating constituent of 3,6-diketocamphane monooxygenase from the CAM plasmid of Pseudomonas putida: the first crystal structure of a type II Baeyer-Villiger monooxygenase. Acta Crystallogr D Biol Crystallogr, 71(Pt 11), 2344-2353. Abstract. Author URL. Full text. Article has an altmetric score of 4
Novak HR, Sayer C, Isupov MN, Gotz D, Spragg AM, Littlechild JA (2014). Biochemical and structural characterisation of a haloalkane dehalogenase from a marine Rhodobacteraceae. FEBS Lett, 588(9), 1616-1622. Abstract. Author URL. Full text. Article has an altmetric score of 1
Kallnik V, Bunescu A, Sayer C, Bräsen C, Wohlgemuth R, Littlechild J, Siebers B (2014). Characterization of a phosphotriesterase-like lactonase from the hyperthermoacidophilic crenarchaeon Vulcanisaeta moutnovskia. J Biotechnol, 190, 11-17. Abstract. Author URL. Article has an altmetric score of 1
Vivoli M, Novak HR, Littlechild JA, Harmer NJ (2014). Determination of protein-ligand interactions using differential scanning fluorimetry. J Vis Exp(91). Abstract. Author URL. Article has an altmetric score of 1
Littlechild J, Sayer C, Isupov M, Ward J, Littlechild J (2014). Structural studies on transaminase enzymes and applications in biocatalysis. NEW BIOTECHNOLOGY, 31, S19-S19. Author URL.
James P, Isupov MN, Sayer C, Saneei V, Berg S, Lioliou M, Kotlar HK, Littlechild JA (2014). The structure of a tetrameric α-carbonic anhydrase from Thermovibrio ammonificans reveals a core formed around intermolecular disulfides that contribute to its thermostability. Acta Crystallogr D Biol Crystallogr, 70(Pt 10), 2607-2618. Abstract. Author URL. Full text. Article has an altmetric score of 1
Sayer C, Martinez-Torres RJ, Richter N, Isupov MN, Hailes HC, Littlechild JA, Ward JM (2014). The substrate specificity, enantioselectivity and structure of the (R)-selective amine : pyruvate transaminase from Nectria haematococca. FEBS J, 281(9), 2240-2253. Abstract. Author URL. Full text. Article has an altmetric score of 2
Holley JE, Slonka J, Littlechild J, Gutowski NJ (2013). An investigation into the presence of pyroglutamyl peptidases in the Alzheimer's disease brain: relevance to pathology?. JOURNAL OF NEUROLOGY, 260, S167-S167. Author URL.
Novak HR, Sayer C, Panning J, Littlechild JA (2013). Characterisation of an L-haloacid dehalogenase from the marine psychrophile Psychromonas ingrahamii with potential industrial application. Mar Biotechnol (NY), 15(6), 695-705. Abstract. Author URL.
Novak HR, Sayer C, Panning J, Littlechild JA (2013). Characterisation of an l-Haloacid Dehalogenase from the Marine Psychrophile Psychromonas ingrahamii with Potential Industrial Application. Marine Biotechnology, 15(6), 695-705. Abstract.
Reid EL, Weynberg KD, Love J, Isupov MN, Littlechild JA, Wilson WH, Kelly SL, Lamb DC, Allen MJ (2013). Functional and structural characterisation of a viral cytochrome b5. FEBS Lett, 587(22), 3633-3639. Abstract. Author URL. Article has an altmetric score of 1
Novak HR, Sayer C, Isupov MN, Paszkiewicz K, Gotz D, Spragg AM, Littlechild JA (2013). Marine Rhodobacteraceae L-haloacid dehalogenase contains a novel His/Glu dyad that could activate the catalytic water. FEBS J, 280(7), 1664-1680. Abstract. Author URL. Full text. Article has an altmetric score of 1
Novak H, Littlechild J (2013). Marine enzymes with applications for biosynthesis of fine chemicals. , 89-106. Abstract.