In May 2017, the Pint of Science festival returned to Norwich. The festival, which is held over a few days, was a huge success, with many events being sold out days in advance. Each event offers the audience the chance to meet scientists at their local pub and discuss their latest research in an informal and welcoming atmosphere, whilst sipping on their favourite pint.

Two sell out events where those of OpenPlant Project Leader Professor George Lomonossoff and his PhD student Roger Castells-Graells, and a second event with OpenPlant’s Norwich-based Director, Professor Anne Osbourn.

George’s talk was entitled ‘Just Eat Your Greens – A New Way of Vaccinating?’ and took place at the York Tavern. It covered the use of a highly efficient transient expression system developed in his laboratory. This Hypertrans® system allows for the relatively quick and cheap production of large quantities of virus-like particles in plants, which have been proven to be effective as experimental vaccines.

Roger presented ‘20,000 Leagues Under the Microscope: Viruses & Nanomachines’ taking the audience on a journey into the nano world of viruses. During the entertaining talks, the audience took part in various activities such as making a virus molecule out of pipe cleaners and creating virus inspired sketches on beer mats.

The following evening, Anne took to the stage at the St Andrews Brewhouse to present her ‘Finding Drugs in The Garden’ talk. Anne’s inspiring talk invited people into the plant kingdom to hear about its very own chemistry toolkit. She presented her teams current work harnessing the DNA that encodes the pathways to these chemicals and using them to produce designer molecules for medicinal, agricultural and industrial applications.

For the scientists taking part in the festival, it has proven to be a great platform on which to reach the public to talk about their research and build an understanding of their work within the local city of Norwich. After such well received talks and events, we very much look forward to the return of the Pint of Science Festival in 2018.

The following article was originally published on the John Innes Centre news feed: Using ‘chemical origami’ to generate customisable, high-value chemicals from plants. Anne Osbourn is Co-Director of OpenPlant and this work from her group is highly relevant to the efforts of OpenPlant to create toolkits for plant metabolic engineering, but was funded from other sources.

Following the discovery of a new and very valuable enzyme which folds linear molecules into different shapes, scientists at the John Innes Centre are building a ‘triterpene machine’ which will enable them to custom-build valuable chemical compounds called triterpenes and produce them in large, cost-effective quantities. Working with the pharmaceutical, agricultural and biotechnology industries, they hope to improve existing triterpenes to make better medicines with fewer side effects, or improve the specificity of pesticides. They also hope to make completely new, custom-designed triterpenes to any specification, which could lead to development of new anti-cancer drugs, agrochemicals, industrial chemicals or cosmetics.

In the ancient Japanese art of origami, different ways of folding a single sheet of paper can transform it into an aeroplane, a flower, or a bird. Plants perform origami too – not with paper, but with chemical compounds, taking individual precursor molecules and using enzymes to fold and modify them to create many different variations.

For several years, Professor Anne Osbourn of the John Innes Centre has been studying the ‘chemical origami’ that gives rise to a large group of plant compounds called triterpenes, many of which may have valuable uses in the pharmaceutical, agricultural and biotechnology industries.

Professor Osbourn said:

“Some triterpenes are currently used in drinks as foaming agents, but there are many more exciting possibilities – new medical therapies such as anti-cancer drugs, diabetes medicines and antidepressants, for example; anti-fungal agents in crop protection, or cosmetic ingredients. All of the triterpenes we know about are based on a suite of similar molecular ‘scaffolds’ – we want to understand how these scaffolds are made, ‘folded’ and ‘decorated’ so that we might be able to engineer completely new triterpenes to make new medicines and industrial chemicals, or to improve those we already have.”

In a new research article published this week in the scientific journal Proceedings of the National Academy of Sciences, Professor Osbourn, along with colleagues at the John Innes Centre and collaborators from the USA, describes how she discovered an important part of the triterpene origami process, almost by accident.

By analysing oat plants that had been exposed to a DNA-mutating chemical, the researchers “stumbled across” a handful of mutated versions of an enzyme called SAD1. SAD1 is a triterpene synthase enzyme responsible for a critical step in building triterpenes: in its normal form, it takes a linear precursor molecule called 2,3-oxidosqualene (OS for short), and turns it into a pentacyclic scaffold – a molecule with 5 carbon rings. This is then further modified by other enzymes to produce hundreds of different triterpene compounds.

However, one of the mutated forms, which differed from the normal form by one little change in the enzyme’s structure, produced tetracyclic scaffolds with four carbon rings instead – the scaffold for a completely different set of triterpenes. Incidentally, the same mutation in an equivalent gene from a different plant, Arabidopsis thaliana, gave the same results, suggesting that this ‘molecular switch’ from pentacyclic to tetracyclic triterpene production is conserved between different plant species.

Next, the scientists tried putting the mutant SAD1 gene into yeast, a fast-growing, single-celled organism, to see if it could be used to make large quantities of triterpenes. Here, the team discovered that the SAD1 enzyme favoured dioxidosqualene (DOS) as a substrate rather than OS.

“This was an exciting discovery,” said Professor Osbourn, “because we realised that we could not only modify the enzyme to produce different triterpene scaffolds, but we could also modify the building block to make different more highly oxygenated scaffolds.”

The PNAS article presents just one part of ongoing work by the Osbourn lab to harness the power of genes and enzymes to generate high-value chemicals from plants.

Professor Osbourn said:

“Here at the Norwich Research Park we’re building a ‘Triterpene Machine’; a toolkit of molecular parts we can put into yeast, or a recently developed rapid expression system using tobacco leaves, which we hope will allow us to custom-build valuable triterpenes and produce them in large, cost-effective quantities. Working with the pharmaceutical, agricultural and biotechnology industries, we hope we’ll be able to modify known triterpenes to improve their existing applications – to make better medicines with fewer side effects, or improve the specificity of pesticides, for example. We might even be able to make completely new, custom-designed triterpenes to any specification we want, which could provide us with new anti-cancer drugs, agrochemicals, industrial chemicals or cosmetics. The possibilities are potentially endless!”

This research was funded by the Biotechnology and Biological Sciences Research Council, the John Innes Foundation and a Norwich Research Park Studentship Award.

Image by Ftiercel [Public domain], shared via Wikimedia Commons