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Soapbark discovery offers sustainability booster for global vaccine market

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Newswise — A valuable molecule from soapbark, used as a key ingredient in vaccines, has been replicated for the first time in an alternative host plant, opening up unprecedented opportunities for the vaccine industry.

A research collaboration led by the John Innes Center used the recently published genome sequence of Chilean soapbark (Quillaja saponaria) to track down and map the elusive genes and enzymes in the complex sequence of steps needed to produce the molecule QS-21.

Using transient expression techniques developed at the John Innes Centre, the team reconstructed the chemical pathway in a tobacco plant, demonstrating ‘tree-free’ production of this highly valued compound for the first time.

Professor Anne Osbourn FRS, group leader at the John Innes Centre, said: “Our study opens up unprecedented opportunities for bioengineered vaccine adjuvants. We can now study and improve these compounds to promote the human immune response to vaccines and produce QS-21 in a way that does not rely on soapbark extraction.

Vaccine adjuvants are immunostimulants that prime the body’s response to the vaccine – and are a key ingredient in human vaccines for shingles, malaria and others under development.

QS-21, a powerful additive, comes directly from the husk of soapbark, raising concerns about the environmental sustainability of its supply.

For many years, researchers and industrial partners have been looking for ways to produce the molecule in an alternative expression system such as yeast or tobacco plants. But the complex structure of the molecule and the lack of knowledge about its biochemical journey through the tree have so far prevented this.

Previously Researchers from Professor Osbourn’s group had assembled the first part of the track which constitutes the scaffolding structure of the QS-21. However, the search for the longest complete pathway, the acyl chain that forms a crucial part of the molecule that stimulates immune cells, has remained incomplete.

In a new study published in Nature Chemical BiologyResearchers at the John Innes Center used various gene discovery approaches to identify around 70 candidate genes and transferred them to tobacco plants.

By analyzing gene expression patterns and products, supported by the John Innes Centre’s metabolomics and nuclear magnetic resonance (NMR) platforms, they were able to narrow the search down to the final 20 genes and enzymes that make up the QS-pathway. 21.

First 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 might address issues of scale and toxicity.

“What is very rewarding is that this molecule is used in vaccines and, by being able to make it more sustainable, my project has an impact on people’s lives. “It’s incredible to think that something so scientifically rewarding could bring so much good to society.”

“On a personal level, this research has been extremely scientifically enriching. I am not a chemist, so I could not have done this without the support of the John Innes Center Metabolomics Platform and Chemistry Platform.

The team has partnered with Plant Bioscience Limited PBL (Plant Bioscience Limited) Norwich Limited who are leading the commercialization of this project.

Complete biosynthesis of the potent vaccine adjuvant QS-21 appears in Nature Chemical Biology



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