A scientist in Waterford is collaborating with a colleague in China to find a way to use biological enzymes in chemical production.Dick Ahlstrom reports
Bacteria from England, a molecular biologist from Ireland and a chemist from China are unlikely partners in a research project that could deliver safer drugs. The work is funded under the new Ireland-China Research Collaboration Fund.
Dr Catherine O'Reilly of the Department of Chemical and Life Sciences at Waterford Institute of Technology leads the work here. Her international connection is with Prof Mei-Xiang Wang, director of the Institute of Chemistry in Beijing.
Enzymes, biological catalysts that help make reactions go faster, represent the point of joint interest in this study backed by the Collaboration Fund, which is administered by the Royal Irish Academy and co-funded by Science Foundation Ireland and by the Ministry of Science and Technology in the People's Republic of China.
"We are looking for enzymes for chemistry," says Dr O'Reilly. "They convert one chemical to another chemical."
The chemical industry typically uses chemical catalysts to enable or speed up a series of reactions aimed at producing a particular product. Dr O'Reilly and Prof Wang are attempting to blend biology with conventional chemistry by using biological enzymes as part of the chemical process.
"We are working on particular enzymes which work with nitriles," says Dr O'Reilly. "Nitriles are organic cyanide compounds. They are used as intermediates in a lot of chemical reactions in the pharmaceutical industry."
Dr O'Reilly worked with Prof Wang some years ago when both were based in the UK. They were searching for bacteria that could interact with nitriles, an indication that they produced enzymes that reacted with these substances.
They isolated a particular bacterium in northwest England and studied the proteins produced by the organism. It is this work that the two scientists are now pursuing under the new Collaboration Fund.
They cloned genes from the organism that produced enzymes of interest given their ability to react with nitriles. These genes were built into E coli which now produce the enzymes needed for analysis.
Dr O'Reilly and Prof Wang are interested in these obscure substances because of their potential to transform pharmaceutical production. One of the greatest challenges faced by companies attempting to develop new drugs is "chirality", a term that relates to the "handedness" of a molecule.
A chemical product may come in two forms, as mirror images of one another. They match one another like a right and left hand when palms are placed together, but mismatch when superimposed, as when you place one palm on the back of the other.
Handedness is an essential feature of drug development: one form, or isomer, may provide therapeutic benefit while the other might be a dangerous toxin. The thalidomide tragedy was a classic example of this, with one isomer preventing morning sickness in pregnant women and the other having teratogenic effects on their unborn children.
Companies must therefore ensure that chiral drugs are produced in one form if only one isomer provides a therapeutic effect. Enter Dr O'Reilly and Prof Wang with their enzymes that can force a reaction to proceed towards a single isomer form.
"The enzymes can pick out the particular stereo isomer and do things more specifically than chemical methods," she says. This is one of the "particular reasons for using biology rather than chemistry" when compounding these drugs.
Dr O'Reilly's success in winning support for this work is noteworthy given she is the only institute-based scientist to receive funding.
"It is especially gratifying to lead the only group from outside of the university sector to secure \ from the fund in the current round," she says. Other research activities in Dr O'Reilly's lab involve the use of microbes and their enzymes to detoxify environmental pollutants.