Hot springs like this one, in Yellowstone Park, USA, contain enzymes used in the HOTZYME project.

Biocatalysis Centre

Ground-breaking research into areas such as drug development and cancer treatment is being carried out at the University of Exeter’s Biocatalysis Centre, through investigations into the structure and applications of enzymes.

Academics at the centre work with organisations across Europe to benefit the public and businesses.

Professor Jenny Littlechild, whose interests include biotechnology, explained: “We have three main areas of interest: using enzymes to do chemistry, using them more generally in the commercial arena and using them to combat disease.”

The centre has been awarded two large European grants in the first area: HOTZYME and THERMOGENE.

Both projects could help businesses save time and resource by developing new enzymes that are stable to higher temperatures and in organic solvents used in industrial applications. The enzymes are used to carry out chemistry in a sustainable way, replacing in many cases synthetic chemical methods which require several steps and result in toxic waste that has to be disposed of.  

The Biocatalysis Centre coordinates THERMOGENE and both projects involve a number of partners from academia and industry, including biotech company Novozymes and pharmaceutical firm Sigma-Aldrich.

THERMOGENE could have particular benefits in the development of new and safer drug molecules. When carbon is present in a molecule, the chemical groups around it can be arranged in different ways. Specific enzymes will only work with one of these arrangements producing a product that is purer and has fewer side effects - a fundamental property in drug development.

Professor Littlechild explained: “The classic example is Thalidomide – there were two types, one which treated morning sickness, the other which caused the deformations to children. So it’s vitally important you use the right arrangement.”

The broad commercial use of enzymes includes their use in detergents and food production – collaborations in this area include a research student who is working with consumer goods company Unilever to improve processes. Further work in the area includes enzymes for carbon dioxide capture and bioenergy production.

The Centre is collaborating with the University of Exeter College of Medicine and Health to use enzymes in the fight against disease. Professor Paul Winyard, is looking into the treatment of arthritis and Professor Andrew Hattersley, who was looking at mutations in type two diabetes.

Solutions to similar problems are being sourced in the centre itself. Dr Richard Chahwan, a recent recruit to the University, is investigating the molecular mechanisms of antibody production.

He explained: “Our bodies make antibodies to fight against germs and toxins. On a normal day we produce about four million different antibodies per hour. In extreme cases the mutagenic process - something that can induce mutation - responsible for antibody maturation can go into overdrive, making some people prone to cancer, or underdrive – making them prone to immune deficiencies.  My work is to understand this fine balance.”

“In many patients mutations occur which cause the over- or under-drive. We’ve done tests to understand how this happens – which means we can help model new drugs to treat these problems.”

Dr Chahwan secured funding for a PhD student to investigate the binding of a particular protein to specific histones (proteins found in cells that package and order DNA) from the Biotechnology and Biological Sciences Research Council (BBSRC) South West Doctoral Training Partnership.

He explained: “By discovering why mutations in the protein we’re studying prevent its binding to histones in cells and mice, we can better understand tumorigenesis and immunodeficiencies in human patients.”

Although he’s found his time at the University ‘intense’, Dr Chahwan is enjoying working in the Biocatalysis Centre.

He concluded: “I’ve been having fun and been moderately successful so far! I’ve won an internal grant to develop our facilities and we’re aiming for bigger grants in the future.”