Engineering saponin biosynthesis pathways for bio-production of novel vaccine adjuants
Lead Research Organisation:
John Innes Centre
Department Name: Biochemistry and Metabolism
Abstract
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.
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.
Organisations
People |
ORCID iD |
Anne Osbourn (Principal Investigator) |
Publications
Martin L
(2024)
Complete biosynthesis of the potent vaccine adjuvant QS-21
in Nature Chemical Biology
Polturak G
(2023)
Discovery of isoflavone phytoalexins in wheat reveals an alternative route to isoflavonoid biosynthesis.
in Nature communications
Reed J
(2023)
Elucidation of the pathway for biosynthesis of saponin adjuvants from the soapbark tree.
in Science (New York, N.Y.)
Description | Attended Roundtable meeting to discuss how Government might further help in the UK's engineering biology sector. |
Geographic Reach | National |
Policy Influence Type | Contribution to a national consultation/review |
Description | Visit by Minister of State in the Department for Science, Innovation and Technology |
Geographic Reach | National |
Policy Influence Type | Participation in a guidance/advisory committee |
Description | AO attended Synthetic Biology Industrial Translation Showcase @Synbio_Showcase:Synbite Showcase Programme at the Royal Academy of Engineering 17.11.22 |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Industry/Business |
Results and Impact | The aim of the 1-Day SynbiTECH Showcase was to reflect important issues and changes in the field of synthetic biology/engineering biology. As with the previous SynbiTECH meetings, the focus was primarily be on the development of the U.K.'s industrial and commercial synthetic biology/engineering biology sector. Consequently, the programme did not only reflect industrial and company development, but, also, important associated matters including strategy and policy, finance, policy and biosecurity. |
Year(s) Of Engagement Activity | 2022 |
URL | http://www.synbicite.com/news-events/2022/nov/17/synbicite-showcase-2022/ |
Description | Anne Osbourn meeting with George Freeman MP during visit to Norwich Research Park |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Professional Practitioners |
Results and Impact | Anne Osbourn met George Freeman MP (Minister of State in the Department for Science, Innovation and Technology) as one of the NRP Entrepreneurial Researchers. Professor Anne Osbourn, Founder of Hothouse Therapeutics, spoke about Unlocking Nature's Inaccessible Chemistry. |
Year(s) Of Engagement Activity | 2023 |
Description | Independent review of UKRI Roundtable discussion co-hosted by the Campaign for Science and Engineering & Sir David Grant |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Policymakers/politicians |
Results and Impact | Anne Osbourn was a member of an independent review of UKRI. Roundtable discussion. Co-hosted by the Campaign for Science and Engineering and Sir David Grant. |
Year(s) Of Engagement Activity | 2022 |
URL | https://www.ukri.org/news/ukri-welcomes-independent-review-report/ |
Description | Seminar: "Finding drugs in the garden: Harnessing plant metabolic diversity" in the @IPS2ParisSaclay amphitheater on Tuesday 22nd November at 2 pm |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Professor Anne Osbourn gave a seminar about "Finding drugs in the garden: Harnessing plant metabolic diversity" in the @IPS2ParisSaclay amphitheater on Tuesday 22nd November at 2 pm |
Year(s) Of Engagement Activity | 2023 |