Supervisor
Dr Nicola Patron
Brief summary
Plants produce a wide range of specialised metabolites that are important for surviving stress, and for mediating interactions with bacteria, insects, fungi and other plants. However, we lack knowledge of how most of the molecules are produced. how this rich chemodiversity evolved. This limits our ability to understand how this rich chemodiversity evolved and to identify routes to the sustainable use of valuable and bioactive plant natural products. This project will investigate sesquiterpene lactones (STLs), a sub-class of terpenoids predominantly found in the Asteraceae (sunflower) family. It will elucidate the genetic basis of bioactive STLs, identifying their biosynthetic pathways and using synthetic biology and metabolic engineering approaches to engineer production.
Importance of Research
Understanding the mechanisms of biosynthesis and evolution of plant metabolites is fundamental to explaining their distribution and biological roles. However, while there have been numerous studies mapping their presence and absence, we are only beginning to understand the genetic basis of these metabolites.
The richness of bioactive molecules found in plants also provides a wealth of potential pharmaceuticals, insecticides, flavours and fragrances. However, bioactive are often present in tiny quantities or in a rare or difficult-to-cultivate species. Chemical synthesis has provided easy and cheap access to some natural products but remains challenging or uneconomical for most molecules. In the past decade, aided by advances in genomics and synthetic biology, pathways for high-value natural products have been elucidated enabling scalable production in heterologous species. This project will investigate the genetic basis of bioactive terpenoids found in species of Asteraceae with the goals of enabling pathway reconstruction and engineering, and to further our understanding of metabolite biosynthesis and diversification.
Project Summary
Sesquiterpene lactones (STLs) are a sub-class of terpenoids predominantly found in the Asteraceae (sunflower) family. Bioactivity has been associated with many STLs, most famously the anti-malarial activity of artemisinin. Within their native species, terpenoids often occur in complex mixtures or in a limited number of cell types, reducing accessibility. For example, many STLs are biosynthesised in trichomes, highly specialised epidermal outgrowths. Further, complex stereochemistry limits the feasibility of chemical synthesis. Advances in synthetic biology have accelerated metabolic engineering, enabling biomanufacturing of natural products. However, this requires knowledge of pathway genes, which, for most molecules, remains unknown.
This project will investigate the genetic basis of bioactive STLs found in UK species of Asteraceae to enable pathway reconstruction and to further our understanding of chemodiversification in plants.
What will the successful applicant do?
The student will gain expertise in comparative expression analysis, homology modelling, and phylogenomics to identify candidate genes involved in the expression of valuable and bioactive plant terpenoids. They will validate and characterise candidates by engineering expression in Nicotiana benthamiana and employ synthetic biology approaches to optimise expression and increase yields. In collaboration with scientists at the Royal Botanic Gardens at Kew, they will also have the opportunity to investigate within-species chemical diversity. Depending on the student's interests, they may additionally choose to investigate the evolution and molecular mechanisms of biosynthetic enzymes; advance bioproduction using metabolic engineering approaches; or investigate terpenoid metabolism in trichomes.
This project will provide training in a range of technical skills and techniques including bioinformatics, biochemistry, synthetic biology and metabolic engineering. The student will also be mentored to acquire the skills, independence, and confidence they need to reach their career goals, with a focus on the development of skills in scientific writing, critical thinking, time management, collaboration, and communication
References
Zhou et al (2020) More is better: the diversity of terpene metabolism in plants. Current Opinion in Plant Biology 2020 Jun;55:1-10. doi.org/10.1016/j.pbi.2020.01.005
Golubova et al (2024) Emerging strategies for engineering natural product biosynthesis in Nicotiana benthamiana. Current Opinion in Plant Biology. 81;102611. doi.org/10.1016/j.pbi.2024.102611