TAILORING PLANT METABOLISM (TPM)

PROJECT SUMMARY

Plants not only supply us with food, fuel and fibre, but also serve as a rich source of valuable chemicals, including drugs, dyes, feedstocks for industry, and flavouring and fragrance ingredients. Plants have a remarkable capacity to make many different types of chemicals, some of which are very complex and cannot easily be synthesised artificially. In the TPM Institute Strategic Programme, we will exploit this ability to produce high-value products in crops. To achieve this, we will manipulate metabolism (the chemical reactions within cells), to tailor plants to make new products and also to make higher amounts or combinations of desirable products. Through our basic research on the control of metabolic pathways (i.e. connected series of chemical reactions), we can do this in a predictable way, rather than by trial and error. We will also produce multipurpose plants that make several different useful products. Building on our expertise and informed by market research, we have chosen to focus on two groups of high-value products: (1) lipids, including oils for human and animal health and nutrition, and waxes for industrial uses such as lubricants and cosmetics; (2) phenolic glycosides, natural compounds that can be used as starting materials to make many useful chemicals, including drugs. 

DETAIL

Tailoring Plant Metabolism comprises two product-focused work packages, united by the common scientific theme of understanding and manipulating metabolic pathways. Two crops have been selected as the most appropriate platforms to deliver products and develop underpinning knowledge: oilseeds (specifically the emerging crop Camelina sativa) for high value lipids, and willow (Salix spp.) for phenolic glycosides.

Work Package 1 - High value lipids for health and industry (Lead: Professor Johnathan Napier)

Plant seeds are a reservoir of energy-dense molecules, including oils enriched in triacylglycerols (TAGs) that serve as the primary storage form of fatty acids. TAGs and their component fatty acids not only provide a major dietary calorie source but also serve as a renewable source of hydrocarbons for biofuels and industrial applications. By understanding and exploiting the diversity of lipid biosynthetic pathways in nature, seeds can be used as a canvas for the design and tailoring of biochemical pathways to generate diverse nutritional and industrial oils not found in oilseed crops.

Work package 1 will examine the spatiotemporal regulation of lipid synthesis, using a combination of transcriptomics, lipidomics, mass spec imaging, tracer studies and metabolic modelling. The interactions between endogenous metabolism and introduced biochemical pathways will be analysed using Camelina lines engineered to produce non-native, very long chain polyunsaturated fatty acids. The potential to exploit novel regulatory mechanisms (including nuclear RNA export and targeted protein degradation) will also be explored. Finally, genome editing and conventional genetic improvement will be employed to improve the Camelina germplasm used for engineering (the “chassis”). Together, these approaches will provide a knowledge base to facilitate predictive metabolic engineering of a range of high-value lipids, including polyunsaturated fatty acids with proven health and nutritional benefits, wax esters for the lubricant and cosmetics markets and structured TAGs with desirable properties.

Work Package 2 - Designer Willows: high value phenolic glycosides for health and industry (Lead: Professor Mike Beale)

Willow contains high levels of natural phenolic glycosides which are probably best known for their role in the development of Aspirin but which also offer an alternative route to petroleum-derived chemicals. Application of chemical fingerprinting to Rothamsted’s willow germplasm collections has begun to reveal novel products with new pharmacologies, offering a timely and exciting opportunity to exploit willow chemistry and genes for the development of new medicines. In addition, further chemical diversity, present in abundance in some members of the willow family, offer green chemistry routes to BTX (benzene/toluene/xylene)-derived phenolics for the chemical industry. Furthermore, low-input perennial cropping systems, such as short rotation coppice willow offer opportunities to achieve carbon-neutral production of materials, whilst also providing energy to drive industrial processes for the recovery of those materials, via the established technology of willow chip combustion for power generation.

Work package 2 will combine natural product chemistry, genetics and genomics to design willow varieties producing novel high-value phenolic glycosides for multiple markets. Through a "plug and play" breeding approach, diverse substrates will be united with species-specific biosynthetic modules. Chemical space will be defined via metabolomics screening of the national willow collection. Metabolomic-transcriptomic time course experiments and mQTL analysis of mapping populations will elucidate the salicinoid biosynthetic pathway(s) and their associated regulatory systems. Candidate genes will be characterised in microbial systems and/or RNAi and genome editing of the corresponding genes in the closely related poplar. Models of metabolite flux in willow will arise from stable isotope labelling data and genetic factors influencing metabolism in hybridised genomes will be revealed through 'omics analysis of judicious crosses. Finally, product yields and extraction processes will be optimised, permitting onward industrial exploitation and bioactivity testing of novel pharmacological agents.