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New smells

24 Mehefin 2010

The grain aphid, Sitobion avenae, germacrene D (top), farnesyl diphosphate (below) and a homology model of germacrene D synthase (left)The grain aphid, Sitobion avenae, germacrene D (top), farnesyl diphosphate (below) and a homology model of germacrene D synthase (left)

A team of scientists in the School of Chemistry has been awarded more than £1M to carry out a collaborative study which among other applications could lead to more environmentally-friendly forms of pest control using nature’s own enzymes.

The research will look to develop a synthetic biology approach for predicting the structural characteristics of odorant molecules so as to produce new and more useful versions for use in pest control, and potentially in perfumery through to medicine.

Working in collaboration with the Biological Chemistry Department at Rothamsted Research in Hertfordshire the team has received the award from the Biotechnology and Biological Sciences Research Council and the Engineering and Physical Sciences Research Council.

Many processes of living organisms involve the recognition of small chemical substances acting as signals. Some of the most powerful of these are involved in the sense of smell, or olfaction. For us, these can relate to sophisticated responses to foods and beverages; for lower animals, including pests, extremely important processes in their lives including the location of mates or food sources can depend on such olfactory responses.

Lead researcher, Professor Rudolf Allemann from the School of Chemistry says that his group's work on the production of chemical signals, particularly a group of compounds called sesquiterpenes, has put chemists into a position to use the natural enzymes involved in the bioproduction of such signals to generate novel and potentially more useful sesquiterpene alternatives. Many sesquiterpenes are active as olfactory cues for most animals, and as stress signals even for plants.

The tremendously complex and diverse group of sesquiterpene natural products originate from just one parent molecule called farnesyldiphosphate, which is modified through the action of enzymes called terpene synthases in more than 300 different ways.

Professor Allemann's group has recently developed synthetic methods for making simple changes to farnesyldiphosphate. These analogues are then transformed using natural sesquiterpene synthases to produce novel 'sesquiterpene-like' compounds that are not normally found in nature. It is hoped that these nature-like compounds will have novel and improved biological activities.

The synthesis of such molecules generally requires complex and expensive chemistry that often produce only small amounts of the desired product. The new synthetic biology approach can lead to large amounts of the targets in only one step that uses Nature's enzymes. Professor Allemann stressed that these applications are only possible through a combination of the ‘blue skies’ research in chemical biology pursued by his group at Cardiff and the pioneering work on olfaction at Rothamsted.

At Rothamsted, Professor John Pickett, FRS, is particularly excited at the prospect of using the system by which the olfactory signals are produced to make new odorants that, by definition, will have the necessary structural properties of the original materials so as to maintain high activity. Professor Pickett said:

"Over recent years, considerable research resources have been spent on understanding the recognition processes for small molecular weight chemicals, particularly those active in olfaction, so as to design new and more useful biologically active substances. Although tremendous advances have been made, it is still not possible to design, rationally, chemical alternatives that will fool olfactory receptors in our noses, on the antennae of insects or the chemical receptors in plants."

Recently, new developments were made at Rothamsted, in collaboration with the Max Planck Institute at Jena in Germany, in understanding how proteins involved in insect olfaction interact with moth sex pheromones. However, here we have completely new work, which will use the process by which the odorants are produced naturally to construct new chemicals that could have not only high olfactory activity but also improved physical properties, such as stability against degradation by light and aerial oxidation.

Such compounds would be of great value in pest control. If successful, the work will also provide new insights into the rational design of biologically active compounds generally and could have wider value in virtually all areas of natural sciences where chemical signals are involved including agriculture and pharmaceuticals and may eventually not only lead to new chemical signals but also to improved drugs such as the anticancer agent taxol or the antimalerial artemisinin.

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