Professor Jennifer Littlechild

About me:

I am a biochemist/structural biologist with interests in the structure and mechanism of a range of microbial and human enzymes. I have special interest in industrial biotechnology and biocatalysis. Current research studies involve the structural and mechanistic characterisation of the C-C bond forming enzymes transketolase and aldolase, carbonic anhydrases, vanadium haloperoxidases, Baeyer-Villiger monooxygenases, aminoacylases, novel esterases and lipases, expoxide hydrolases, gamma lactamases, alcohol dehydrogenases, dehalogenases, transaminases,cellulases and other enzymes from thermophilic bacteria and archaea. Many of these enzymes are used in combination with conventional chemical synthesis for the production of new high value optically pure drugs of interest to pharmaceutical companies. Other enzymes have applications within the healthcare industries and in different areas of industrial biotechnology.

Interests:

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,expoxide hydrolases, lactonases,cellulases 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,Unilever and Evonik. I have co-ordinated grants with DTI and Innovate, UK and have been involved in EU grants within framework 4,6 and 7 and ERA-net and ERA-CoBiotech in 2017. I am Vice-Chair and 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).

Other collaborations with Prof Brophy, Aberystwyth on the structural investigation of nematode specific GST proteins. Structural studies on novel plant enzymes from the vitamin C pathway and involved in fungal infection with Exeter colleagues. Russian Academy of Sciences for thermophilic transfer enzymes and thermophilic cell factories, Prof Nils Birkeland,Bergen, Norway and Prof Peter Schoeheit, University of Keil, thermophilic transfer enzymes, Dr Daniela Monti, ICRM, Milan, Italy for thermophilic transfer enzymes. Prof Siebers, Essen, Germany for extremolyte production in thermophilic bacteria and archaea.

Qualifications:

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 Head of Biocatalysis within the Bioeconomy 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 Institute fur Molekular Genetik, Berlin, Germany
1974-1975 Postdoctoral Fellow, Department of Biochemical Sciences, Princeton University, USA
1974 Department of Biochemical Sciences, Princeton University, USA
1973 Department of Biophysics, Kings College, University of London