Professor Jenny Littlechild with a member of her research group

Professor Jenny Littlechild with a member of her research group

Professor Jennifer Littlechild
Professor of Biological Chemistry

Research

Research 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 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.

Research projects

Exploration of Novel Host Organisms as Cell Factories
Industrial studentship Glaxo Smith Kline
October 2012 – Sep 2016

THERMOGENE ERA-inet Industrial Biotechnology
With SME in Russia Moltech and partners in Norway and Germany
BBSRC funded in UK
March 2013- Feb 2016

EU Large Consortium Grant ‘Hotzyme’ Biocatalysis Centre
International Companies – Sigma Aldrich and Novozymes, SMEs and academic partners,
1st April 2011-31st March 2015

Unilever GrantEnzyme Stabilisation – Intervention Routes Industrial grant                          
Dec 2011-Nov 2012
Extension for Dec 2012
Extension Jan 2013 – Dec 2013

Statoil Industrial Grant –Investigating Kinetics of Enzymes in Microreactors
Jan 2012 – Dec 2012 

Succinate Dehydrogenase as a target for anti-microbial and anti-fungal fluorinated compounds
iNET Award with local company Darr House (SME) with Dr Steven Bates
May 1st 2011

KTN SPARK Award with Gwent Group, UK (SME)
Identification, Expression, Purification and Analysis of Novel Thermophilic Alcohol Oxidases
(Funding from Tech. Strategy Board, EU, Defra and BBSRC)
Feb 14th 2011 – August 13th 2011

Characteristion of novel enzymes from the marine algal virus EhV-86 and evaluation of their use for commercial biocatalysis
BBSRC Studentship CASE partner PML Cooperation Ltd
10-2007 - 09-2011

Novel Halogenating and Dehalogenase enzymes from marine microbes
BBSRC Studentship CASE partner Aquapharm
10-2007 - 09-2011

Starch Degrading Enzymes  
Industrial Project Diversa, USA ,

Dehydrogenases of Importance in Drug Development
Industrial Project York Pharma, UK  
2005 - 2007

Commercial exploitation of Marine Enzymes
DTI Fasttrack with Aquapharm, Oban   
12-2006 - 11-2008

Baeyer-Villiger Enzymes and Application in Biotransformations
BBSRC
12-2005 - 1-2008

High Throughput Biocatalytic Synthesis and Screening in Micro Reactors
EPSRC
07-2005 - 06-2008

Effective and Substainable Control Strategies for Liver Fluke in Europe
EU Framework 6
005  - 2008

Research networks

  • South West Structural Biology Consortium, UK
  • Collaborations with UCL London, Prof. J. Ward, Biochemistry and Dr Paul Dalby and Prof. John Woodley, Biochemical Engineering, University of Copenhagen 
  • EU Network on Baeyer-Villiger Monooxygenases. DSM, Germany, Fluka, Switzerland, Academic partners in France, Holland and Italy
  • EU Network on Thermophilic hydrolase enzymes, Hotzyme with Sigma-Aldrich, Novozymes and SMEs, University of Copenhagen Denmark, University of Essen, Germany, Montana State University, USA,Wageningen University, Netherlands,ICRM, Milan, Italy, National Hellenic research foundation, Greece, EuCRF, Israel.
  • ERA-IB Network on Thermophilic Transferase enzymes with Russian Academy of Sciences, University of Bergen, Norway, University , University of Keil, Germany and SME Moltech.
  • COST Action Cascat
  • RedCat network, Saarbrucken University, Germany
  • Japan Partnership Award, BBSRC with Prof. Izumi, Prof. Oshima, Japan
  • Pro-Bio Faraday grouping, UK
  • Knowledge Transfer Network in Marine Biotechnology
  • INSTRUCT European Structural Biology Network

Research grants

  • 2006 PML Corporation
    Plymouth consultancy
  • 2006 Diversa, USA.
    Starch Degrading Enzymes
  • 2006 DTI
    Commercial exploitation of Marine Enzymes
  • 2005 BBSRC
    Baeyer-Villiger Enzymes and Application in Biotransformations
  • 2005 EPSRC
    High Throughput Biocatalytic Synthesis and Screening in Micro Reactors
  • 2005 EU Framework 6
    Design of Effective and Substainable Control Strategies for Liver Fluke in Euorpe
  • 2004 BBSRC
    Structural Studies of Enzymes Important in Biocatalysis and Drug Design REI Equipment Initiative
  • 2004 Alphamerix/Alpha Alchemy, Cambridge/Pro-Bio Faraday
    The application of thermostable alcohol dehydrogenases and lipases to medicinal biocatalysis
  • 2004 Chirotech/Dow Pharma, Cambridge.
    Optimisation of the use of thermophilic alcohol dehydrogenase enzymes for the synthesis of novel chiral alcohols of interest to pharmaceutical industry
  • 2003 TMO Renewables UK
    Dehalogenase Enzymes.
  • 2003 Exeter,UK
    Acetylation of transcription factors in relation to Oxidative Stress Affiniti/Biomol
  • 2002 BBSRC
    The Exploitation of Vanadium Haloperoxidase Enzymes in Applied Biocatalysis
  • 2002 BBSRC Japan Partnership Award.
    Development of Novel Thermostable Biocatalysts
  • 2002 Diabetes, UK.
    Glucokinase-Structure and Function Relationships to Normal and Diabetic Forms
  • 2002 EPSRC Pro-Bio Faraday Industrial Studnetship/Stylacats, Live
    Thermophilic Nitrilase Enzymes
  • 2002 Applied Genomics Centre ESRC
    10% Time commitment.
  • 2002 BRA
    Oxidative stress/Rheumatics
  • 2002 Chirotech/Dow Pharma, Cambridge.
    Human pyroglutamyl carboxypeptidase and inhibitor development
  • 2001 BBSRC
    Structural Studies on two Gamma Lactamase Enzymes with Opposite Stereospecificity
  • 2001 Torbay Hospital Devon.
    Non-Enzymically induced amino acid racemization in human proteins a possible contributory factor in metabolic dysfunction and complications of diabetes mellitus
  • 2000 Glaxo-Wellcome.
    The bromoperoxidase from marine algae Corallina officinalis
  • 2000 Chirotech/Dow Pharma, Cambridge.
    Thermostable ADH enzymes from the archaea Sulpholobus and Pyrococcus species:applications in chiral drug synthesis
  • 2000 Chirotech/Dow Pharma, Cambridge.
    Characterisation of lactamase (amidohydrolase) enzymes of commercial value for chiral drug synthesis.
  • 2000 Chirotech/Dow Pharma, Cambridge.
    Thermostable archaeal esterase enzyme and its application for chiral drug synthesis.

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