New Smells Through Synthetic Biology

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 virtually all areas of natural
sciences where chemical signals are involved including agriculture and
pharmaceuticals.

About Cardiff School of Chemistry
The School of Chemistry is one of the largest chemistry schools in the UK, and both teaching and research benefits from a multi-million pound investment in laboratories and other facilities.  The joint strengths are of academic excellence within the School and extensive industrial contacts outside. The School conducts industry-relevant research, focusing on six areas: surface science and catalysis; structural and computational chemistry; organic synthesis; co-ordination and speciation chemistry; magnetic resonance spectroscopy; and materials chemistry. Research income has increased more than threefold in recent years, including a substantial increase in industrial funding. It is also home to two of only six national centres that are funded by the Engineering and Physical Sciences Research Council.  These are the X-ray Diffraction Centre and the ENDOR centre.
Visit the School’s website at: www.cardiff.ac.uk/chemy

About Cardiff University
Cardiff University is recognised in independent government assessments as one of Britain’s leading teaching and research universities and is a member of the Russell Group of the UK’s most research intensive universities.  Among its academic staff are two Nobel Laureates, including the winner of the 2007 Nobel Prize for Medicine, Professor Sir Martin Evans.  Founded by Royal Charter in 1883, today the University combines impressive modern facilities and a dynamic approach to teaching and research. The University’s breadth of expertise in research and research-led teaching encompasses: the humanities; the natural, physical, health, life and social sciences; engineering and technology; preparation for a wide range of professions; and a longstanding commitment to lifelong learning.
Visit the University website at: www.cardiff.ac.uk

About Rothamsted Research
Rothamsted Research is based in Hertfordshire and is one of the largest agricultural research institutes in the country. The mission of Rothamsted Research is to be recognised internationally as a primary source of first-class scientific research and new knowledge that addresses stakeholder requirements for innovative policies, products and practices to enhance the economic, environmental and societal value of agricultural land. The Applied Crop Science department is based at Broom’s Barn, Higham, Bury St. Edmunds. North Wyke Research is located near Okehampton in Devon. Rothamsted Research is an institute of the Biotechnology and Biological Sciences Research Council. For further information, please contact the Rothamsted Research Press Office. Dr Sharon Hall (Tel: +44 (0) 1582 763 133 ext 2757 or email sharon.hall@bbsrc.ac.uk or Dr Adlia de Paula (Tel: +44 (0) 1582 763 133 ext 2260 or email adelia.depaula@bbsrc.ac.uk

About BBSRC
The Biotechnology and Biological Sciences Research Council (BBSRC) is the UK funding agency for research in the life sciences. Sponsored by Government, BBSRC annually invests around 470M in a wide range of research that makes a significant contribution to the quality of life for UK citizens and supports a number of important industrial stakeholders including the agriculture, food, chemical, healthcare and pharmaceutical sectors. BBSRC carries out its mission by funding internationally competitive research, providing training in the biosciences, fostering opportunities for knowledge transfer and innovation and promoting interaction with the public and other stakeholders on issues of scientific interest in universities, centres and institutes.
For more information see www.bbsrc.ac.uk