Finding drugs in the garden: harnessing plant metabolic diversity for therapeutic applications

Plants produce a wealth of natural products. The vast majority of the natural product diversity encoded by plant genomes remains as yet untapped. The explosion in plant genome sequence data, coupled with affordable DNA synthesis and new DNA assembly technologies, now offer unprecedented opportunities to harness the full breadth of plant natural product diversity and generate novel molecules in foreign hosts using synthetic biology approaches. The recent discovery that genes for the synthesis of different kinds of natural products are organised in biosynthetic gene clusters in plant genomes opens up opportunities for mining for new pathways and chemistries. This advance, in combination with powerful new transient plant expression technology, is enabling the development of rational strategies to produce known and new-to-nature chemicals tailored for food, health and industrial applications. This presentation will focus on our work on developing a translational synthetic biology pipeline for rapid preparative access to plant natural products and novel analogs using synthetic biology approaches, focusing in particular on the elucidation of the pathway for saponin vaccine adjuvants from the Chilean soapbark tree. Our results enable for the first time the production of soapbark vaccine adjuvants in heterologous expression systems and open the way for new routes to access and engineer natural and new-to-nature immunostimulants. Chapters 00:00 Bioactive compounds from botanicals 04:29 From wheat disease to triterpenoid research 11:26 Beads on a string - why do biosynthetic pathway genes cluster? 19:45 From in silico to lab - utilising transient assays for high throughput investigations of complex pathways 27:04 The QS-21 pathway 45:26 How machine learning can predict bioactivity of new-to-nature compounds and the steps needed to produce them Speaker profile: Professor Anne Osbourn OBE FRS NAS Anne Osbourn is a Group Leader at the John Innes Centre working on plant natural products. Her discovery that in plant genomes the genes needed to make particular natural products are often organised in clusters like ‘beads on a string’ has greatly accelerated the discovery of new pathways and chemistries. She has established a synthetic biology platform based on transient plant expression that provides rapid access to previously inaccessible compounds and analogs at gram scale. These two step changes open up new routes to combine genomics and synthetic biology to synthesize and access previously inaccessible natural products and analogs for medicinal, agricultural and industrial applications. Anne was awarded the Novozymes 2023 Award in recognition of her scientific contributions. She is also a poet, and has developed and co-ordinates the Science, Art and Writing (SAW) Initiative (www.sawtrust.org), a cross-curricular science education outreach programme. Her prize-winning poetry collection ‘Mock Orange’ was published in 2020. More on producing the drugs and vaccines of the future: https://www.plantsciencefutures.org.u... Filmed at the Gatsby Plant Science Summer School, 2025. #bioactivecompounds #drugdiscovery #transientexpressionsystem #biochemistry #plantbiology #syntheticbiology #genomics #plantscience #plantresearch