Verrucosispora maris, the bacteria in which the enzyme was found. Credit: P. Race
Scientists at the Universities of Bristol and Newcastle have uncovered the secret of the ‘Mona Lisa of chemical reactions’ – in a bacterium that lives at the bottom of the Pacific Ocean. It is hoped the discovery could lead to the development of new antibiotics and other medical treatments. The Diels-Alder reaction, discovered by Nobel Prize-wining chemists Otto Diels and Kurt Alder, is one of the most powerful chemical reactions known, and is used extensively by synthetic chemists to produce many important molecules, including antibiotics, anti-cancer drugs and agrochemicals.
However, there has been much debate and controversy about whether nature uses the reaction to produce its own useful molecules. Now, researchers at BrisSynBio, a BBSRC/EPSRC Synthetic Biology Research Centre at the University of Bristol and the School of Biology at Newcastle Uni have conclusively shown that a true ‘Diels-Alderase’ (Diels-Alder enzyme) exists. They have also established in atomic detail how it catalyses the reaction.
Dr Paul Race said: “We found the enzyme, called AbyU, in a bacterium called Verrucosispora maris (V. maris), which lives on the Pacific seabed. V. maris uses the AbyU enzyme to biosynthesise a molecule called abyssomicin C, which has potent antibiotic properties.” To establish the details of how the AbyU enzyme catalyses the Diels-Alder reaction, the team first had to solve the atomic structure of AbyU, and then simulate the enzyme reaction using quantum mechanics methods. Dr Race said: “Once we had figured out how AbyU was able to make natural antibiotic, we were able to show that it could also perform the Diels-Alder reaction on other molecules that are difficult to transform using synthetic chemistry.”
The team are now investigating ways of using the enzyme to make molecules similar to abyssomisin C, in the hope that antibiotics are found that are even more effective than the natural molecule.
Dr Jem Stach, from Newcastle University, was also a co-author of the paper. He said: “Nature, not only in the compounds it produces, but also the means by which it does so, is the best chemist. This has never been clearer to me than it was during this collaboration between biologists and chemists. Starting with genome gazing, and ending with new chemistry, on a journey that took in structural biology, synthetic chemistry and computational chemistry, was utterly rewarding, educational and fascinating.” http://www.bristol.ac.uk/news/2016/may/enzyme-antibiotic-discovery.html
Recent Comments