Scientists have successfully replicated a valuable molecule found in the soap bark tree in an alternative host plant, which opens unprecedented opportunities for the vaccine industry.
A research collaboration led by the John Innes Center used the recently released genome sequence of the Chilean Soap Bark Tree (Quillaja saponaria) to identify and map the elusive genes and enzymes in the complex sequence necessary for the production of the molecule QS-21.
Using transient expression techniques developed at the John Innes Centre, the team reconstructed the chemical metabolic pathway in a tobacco plant and demonstrated for the first time the production of this highly regarded compound „freely from the tree“.
„Our study opens unprecedented possibilities for vaccine adjuvant biotechnology. We can now investigate and improve these compounds to enhance the human immune response to vaccines and produce QS-21 in a way that does not depend on extraction from the soap bark tree.“
Professor Anne Osbourn FRS, Group Leader at the John Innes Center
Vaccine adjuvants are immunostimulants that trigger the body’s response to the vaccine- and are an important component of human vaccines for shingles, malaria, and other vaccines in development.
QS-21, an effective adjuvant, is directly extracted from the bark of the soap bark tree, raising concerns about the ecological sustainability of its supply.
For many years, researchers and industry partners have been searching for ways to produce the molecule in an alternative expression system such as yeast or tobacco plants. However, the complex structure of the molecule and a lack of knowledge about its biochemical pathway in the tree have previously prevented this.
Previously, researchers in Professor Osbourn’s group had assembled the early part of the signaling pathway that forms the scaffold structure for QS-21. However, the search for the longer complete pathway that forms the acyl chain, a crucial part of the molecule that stimulates immune cells, remained incomplete.
In a new study published in Nature Chemical Biology, researchers at the John Innes Center used a series of gene discovery approaches to identify about 70 candidate genes and transferred them to tobacco plants.
By analyzing gene expression patterns and products, supported by the Metabolomics and Nuclear Magnetic Resonance (NMR) platforms at the John Innes Centre, they were able to narrow down the search to the last 20 genes and enzymes that make up the QS-21 signaling pathway.
Lead author Dr. Laetitia Martin said: „This is the first time that QS-21 has been produced in a heterologous expression system. This means we can better understand how this molecule works and how we can address issues with size and toxicity.“
„What is so rewarding is that this molecule is used in vaccines and that my project has an impact on people’s lives by making it more sustainable. It’s amazing to think that something so scientifically rewarding can bring so much good to society.“
„On a personal level, this research has been scientifically rewarding. I’m not a chemist, so I couldn’t have done this without the support of the Metabolomics platform and the chemistry platform at the John Innes Center.“
The team has collaborated with Plant Bioscience Limited PBL (Plant Bioscience Limited) Norwich Limited, which is leading the commercialization of this project.
The full biosynthesis of the effective vaccine adjuvant QS-21 appears in Nature Chemical Biology.
Martin, LBB, et al. (2024). Complete biosynthesis of the effective vaccine adjuvant QS-21. Nature Chemical Biology. doi.org/10.1038/s41589-023-01538-5.