Engineering saponin biosynthesis pathways for bio-production of novel vaccine adjuants

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Plants are a rich source of drugs and other high-value compounds. During the nineteenth century, advances in chemistry enabled many bioactive natural products to be purified from plants and their structures determined, paving the way for the emergence of the pharmaceutical industry. The first naturally derived pure medicine to be commercialized was morphine, extracted from opium Merck in 1826. Subsequently efforts were made to make natural products by chemical synthesis, the first example being salicylic acid, produced commercially by Bayer in 1899. However, despite these and other successes, the vast majority of plant metabolic diversity has remained untapped due to the problems of accessing source species, purifying compounds and the challenges of chemical synthesis. The ability to decode the chemical potential of plants by sequencing their transcriptomes and/or genomes and to then use this information as an instruction manual to make drugs and other high-value chemicals is opening up new routes to harness the vast chemical diversity of the Plant Kingdom. We have established transient plant expression technology for the rapid reconstruction of plant metabolic pathways and demonstrated that this system can be used to access gram-scale quantities of products. This technology is readily scalable and has been used for commercial production of vaccines. This project is intended to demonstrate that plant-based metabolic engineering is a viable route to the commercial production of pharmaceuticals (and other high-value compounds), and also a credible platform for the generation of molecular diversity and new product discovery. The focus of the proposed work is on engineering saponin biosynthesis pathways for bio-production of novel vaccine adjuvants. The outputs have the potential to broaden the diversity of available adjuvants and expand the resources and the capabilities of the vaccines industry as a whole, to the benefit of the industry and society.