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New Smells Through Synthetic Biology

1 February 2010

Scientists in the School of Chemistry Cardiff University and at the Biological Chemistry Department at Rothamsted Research have received an award worth over £1 million by the Biotechnology and Biological Sciences Research Council, together with the Engineering and Physical Sciences Research Council, 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.

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, says that his group's work on the production of chemical signals, particularly a group of compounds called sesquiterpenes, many of them active as olfactory cues for most animals, and as stress signals even for plants, 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. 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 at Cardiff have 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.  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.

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 perfumery through to medicine.