The understanding of nature’s involvement in a deceptively simple chemical reaction may help in the future development of new antibiotics.
Scientists at the University of St Andrews have discovered how nature makes the ‘last ditch’ antibiotic vancomycin. By unlocking the chemistry behind the biosynthesis of the superbug-fighting drug, the researchers hope they and others can use their knowledge to develop new treatments for infections now resistant to vancomycin itself.
Vancomycin, used to treat infections in many different parts of the body, was introduced forty years ago to treat new strains of bacterial infections that were growing resistant to penicillin. It became known as the last resort antibiotic because it was widely used to kill bacteria when no other drug worked, but over the years strains of bacterial infections (or superbugs) such as vancomycin-resistant enterococci (VRE) have gained resistance against vancomycin itself.
During vital enzyme research the St Andrews researchers Dr Changjiang Dong and Professor James Naismith discovered nature’s role in the chemical reaction vital or the production of vancomycin. The important discovery, published in this week’s edition of Science, lay in nature evolving a specific process to control the addition of a single chlorine atom into a specific site of a molecule. If chlorine is put in the wrong place the molecule does not work.
Dr Dong, a senior researcher, said: “Nature is making ordinary bleach. Normally this is useless for doing controlled chemistry. However, nature has evolved a very specific way of doing this chemistry that had not been thought possible.”
The researchers hope that they can modify the key enzymes involved to create new, more powerful antibiotics.
Professor James Naismith added: “This insight was only possible once we determined the structure of the enzyme, tryptophan 7 halogenase. It suggests that in the future we may be able to modify these enzymes to create novel antibiotics.”
The research is in collaboration with a group in Dresden, Germany which is led by Professor Karl- Heinz Van Pee.
Part of the work was carried out by the Scottish Structural Proteomics Facility, a shared facility between the Universities of St Andrews and Dundee funded by SHEFC (Scottish Higher Education Funding Council) and the BBSRC (Biotechnology and Biological Science Research Council). The research is supported by the BBSRC.
The scientific paper ‘Tryptophan 7- Halogenase (PrnA) Structure Suggests a Mechanism for Regioselective Chlorination’ by Changjiang Dong, Silvana Flecks, Susanne Unversucht, Caroline Haupt, Karl-Heinz van Pee, and James H. Naismith is published in Science (30 September 2005: 2216- 2219).
NOTE TO PICTURE EDITORS;
IMAGES ILLUSTRATING THE RESEARCH ARE AVAILABLE FROM THE PRESS OFFICE – CONTACTS BELOW.
Dr Dong and Professor Naismith holding a model of 7- chlorotryptophan. The enzyme places the chlorine atom (green ball) at only one place in the molecule.
The structure of PrnA the enzyme responsible for the addition of chlorine to tryptophan.
Issued by Beattie Media On behalf of the University of St Andrews Contact Gayle Cook, Press Officer on 01334 467227 / 462529, mobile 07900 050 103, or email gec3@st- andrews.ac.uk Ref: Nature’s role in creating cures 051005 View the latest University press releases at http://www.st- andrews.ac.ukResearch