Pace is quickening in enzyme research

Enzymes play a central role in a whole range of industrial, pharmaceutical and food-manufacturing processes, and developing new…

Enzymes play a central role in a whole range of industrial, pharmaceutical and food-manufacturing processes, and developing new ones or modifying existing enzymes is therefore big business. If you build a better enzyme, the world will beat a path to your door.

They are essential to the processes of life and are produced inside cells to make things happen. They act as biological catalysts, chemicals that can accelerate specific biochemical reactions without themselves being altered.

Enzymes are proteins and are the direct products of individual genes. This means they are highly specific and tend to react with a partner chemical in the cell. A good analogy is the lock-and-key or hand-and-glove relationship.

These chemicals remain reactive and useful outside the body, however, and with the correct kind of match-up can do useful things. The most familiar example is the enzymes which are added to laundry detergent to enhance cleaning of difficult stains at low temperatures. Without enzymes many stains would not come out of fabrics unless they were washed to destruction.

READ MORE

Enzymes are also problematic chemicals. Many potentially useful enzymes are fragile and will "denature" or change their chemical structure if heated or placed in harsh chemical environments. The proteins in egg whites denature when heated, changing from a runny, transparent fluid to a white solid.

Dr Ciaran Fagan of the School of Biotechnology at Dublin City University has been studying enzymes for almost a decade, in particular trying to find ways to "toughen them up". The object, he said, was to improve heat tolerance, develop enzymes that can survive organic solvents and produce versions that work longer before they denature.

He has done specific research on trypsin, a digestive enzyme and peroxidase, a versatile enzyme that is used in a remarkable range of processes from cold DNA probes to washing powders. His laboratory is currently part of an EU-funded project which involves nine commercial and third-level research labs in Ireland, Britain, Sweden, Italy and Denmark.

Peroxidase is used as a catalyst in fine chemical manufacture and can be used to clean up chemical pollutants including phenols in drinking water, Dr Fagan said.

It has major applications as an "indicator", a reactive substance in diagnostic tests that either changes colour or luminesces in the presence of certain other chemicals. It is used in urine test strips and tests for pathogens such as HIV and hepatitis.

The aim of his research is to reduce the fragility of peroxidase and other enzymes so they can be used in a wider range of applications. Enzymes work because they have a precise molecular structure. The specific shape of the enzyme interacts with a matching indentation in the proteins they catalyse, so if their shape changes they don't work.

He is developing chemical treatments to strengthen the enzyme's structure. "One of the main chemicals we use is two-ended, with reactive compounds at both ends," he said. These reactive substances target specific amino acids in the enzyme and once hooked up, the chemical strengthens the enzyme, "stapling" it into a fixed position and helping to hold it firm.

Another approach involves an intensive study of the protein's crystalline structure. Once visualised on a computer, the researchers can "tweak" the enzyme on screen, using certain additional molecules to reinforce the weak points, hopefully leading to a more durable enzyme.

Yet another line of attack sees an inert coating substance, polyethylene glycol, being attached to the enzyme molecules. Once latched on to the enzyme it helps to stop it denaturing and changing shape.

Approaches in other labs include recombinant DNA techniques and the exploitation of bacteria able to grow in extreme temperature or chemical situations. What works for one enzyme might not work for another. Success, however, can bring improved yields and less polluting processes.