Winner: 2022 Corday-Morgan Prize
Rebecca Goss
University of St Andrews
For pioneering the use of enzymatic halogenation/cross-coupling in C‒H activation.
More than 90% of pharmaceuticals are manufactured using a process called halogenation which bonds carbon to a halogen (typically chlorine, bromine or iodine) 鈥� called a C-X bond. More than 20%, including drugs such as Claritin, retain this halogen (X-factor) in the final product; it gives the drug its activity and makes sure that it is properly processed by the body. Drugs containing this X-factor are used to treat medical conditions such as cancer, diabetes, high cholesterol, stomach ulcers, anaemia, asthma, epilepsy, and others. Whilst the ability to selectively make C-X bonds is essential, current chemical halogenation methods to achieve this are inefficient, expensive and require toxic chemicals, with significant supply chain fragility. Current processes are often accompanied by poor selectivity, which results in unspecific halogenation and undesired by-products, creating difficulties in the downstream purification process and environmentally detrimental waste. Professor Goss and her team use cheap, easy to handle and readily available salt (nothing more than common table or sea salt), and, with an enzyme, can precision edit even quite complicated molecules, to add in a C-X bond. They have found a way of mining for new enzymes, searching uncharted gene sequences directly 鈥� a little like a 鈥檞ord search鈥�. Their approach can, for the first time, be used to directly reveal C-X forming enzymes. A C-X bond is like a gateway to access almost any other chemical substitution. In this way, the team can use their halogenase enzymes for C-H activation and diversification. Using these enzymes in parallel with the mild aqueous conditions that the team have developed, they can selectively change a C-H bond into C-almost anything. And they can develop these reactions so that they work even in a living cell.
Biography
Professor Rebecca Goss FRSC FRSE heads a vibrant multidisciplinary and translational research group. Her cutting edge and diverse work on discovery and engineering of medicinally relevant natural products, and developing new tools that enable the fusion of synthetic chemistry and synthetic biology, has resulted in her being invited to give over 160 lectures internationally. As the first female professor of organic chemistry at the University of St Andrews, Rebecca is passionate about inspiring and encouraging the next generations into science. She works hard to equip early career researchers with the skills they need and is most proud of the fact that of her 34 group alumni 12 out of 22 have gone into academia internationally and are already principal investigators. A further 10 have been employed in industry and many are already in positions of leadership. 鈥楴omenclature鈥�, her funded project with the internationally acclaimed poet, Rebecca Goss, is designed to dispel, in front of a wide audience, the still engrained misperception that a career in science is incompatible with being a mum. Rebecca is CEO and co-founder of X-Genix. The company builds upon patented and proven disruptive technology for C-X bond formation. A reaction central to the manufacture of over 90% of small molecule drugs as well as an important tool for drug discovery. X-Genix has received the AccelerateHER Disruptive Technology Award 2021. She grew up on the Isle of Man, interested from an early age in engineering, the natural world, and business. Her academic career has been pioneering, disruptive and highly translationally facing, with a focus on finding and developing solutions for molecule building and human health.
I was told by a family member that I didn't have a scientific bone in my body, but that didn't stop me being excited and interested in chemical reactivity, and the molecular mechanisms that underpin life.
Professor Rebecca Goss
Q&A with Professor Rebecca Goss
How did you first become interested in chemistry?
When I was 10鈥� 12, I wanted to become an artist. However, I had two particularly inspiring chemistry teachers. Mr Arthur Looney (A Looney) who demonstrated so many beautiful chemical reactions to us, as well as showing us just how much sugar could be dissolved in water (for his bees). Mrs Wendy Amos, who later left to join her husband, Professor Amos, and study toward her PhD.
I was particularly interested in the chemistry of life, but rather than wanting to memorise cycles, I wanted to understand it from principles of thermodynamics/reactivity.
I actually started on a biology degree, but moved quickly back to a full chemistry degree so that I could gain a deeper understanding and then apply this to biological systems.
Who or what has inspired you?
Jim Staunton, Peter Leadlay, Tu Youyou and my daughter Esther.
I was blown away when Jim Staunton showed a cartoon of the beautiful multifunctional enzymatic machinery that make up polyketide synthases: powerful machines that make many of the most medicinally important antibiotics, immunosuppressants and anticancer agents.
The chemistry of these molecules are so complex, yet these systems have exquisite control at each stereo centre.
The opportunity to engineer these machines was so apparent and so exciting.
What motivates you?
The opportunity to do good.
The excitement of discovering something that no one has seen before.
A Hebrew poem states: It is the glory of God to conceal a matter; to search out a matter is the glory of kings. It is indeed glorious to find a new molecule or a new enzyme.Getting to work with my wonderful, fun and diverse research team, as well as the other wonderful scientists across the world that I work with.
What advice would you give to a young person considering a career in chemistry?
It is so very fascinating and rewarding. Go for it! It is important to chase your dreams and passions and ignore naysayers.
I was told by a family member that I didn't have a scientific bone in my body, but that didn't stop me being excited and interested in chemical reactivity, and the molecular mechanisms that underpin life.
I was also told by student peers a long time ago that it was natural selection and that women couldn't become chemists, as they put all of the chemicals that I needed on the very highest shelves and removed the kick stool. Probably not good lab practice, but I evolved and traded my Doc Martin's for heels.
Can you tell us about a scientific development on the horizon that you are excited about?
We have some exciting new GenoChemetic tags and diversification chemistries coming through including very cool chemistries moving from sp3 to sp2 which we will submit for publication soon, (work of a very talented PhD system).
We are also in the process of spinning out X-Genix.
Why is chemistry important?
It underpins natural life. It underpins society from crop production, to materials and dyes, from computing to pharmaceuticals. Everything!
What does good research culture look like/mean to you?
Promotion of integrity, promotion of excellence, promotion of work life balance, promotion of inclusivity.
How are the chemical sciences making the world a better place?
In every way, but chemistry is so pervasive it often goes unnoticed.
Without chemistry we would not have pharmaceuticals, materials, agrochemicals, food preservatives, refrigerants 鈥� and it underpins everything.
Why do you think teamwork is important in science?
It is critical, and the more diverse the team the more creative the ideas. Diversity in terms of disciplinarily, as well as diversity in terms of culture.
What is your favourite element?
Group 7, and it鈥檚 hard to choose between them:
When I was 11, I named one of my cats Astatine.
F makes such a large contribution to medicine, and yet there are only ~13 naturally occurring organofluorides.My current favourite is probably iodine.