Elucidation of the pathway for biosynthesis of saponin adjuvants from the soapbark tree

• 成果类型: Article
• 署名作者: Reed, James; Orme, Anastasia; El-Demerdash, Amr; Owen, Charlotte; Martin, Laetitia B. B.; Misra, Rajesh C.; Kikuchi, Shingo; Rejzek, Martin; Martin, Azahara C.; Harkess, Alex; Leebens-Mack, Jim; Louveau, Thomas; Stephenson, Michael J.; Osbourn, Anne
• 署名单位: UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); John Innes Center; HudsonAlpha Institute for Biotechnology; University System of Georgia; University of Georgia; Egyptian Knowledge Bank (EKB); Mansoura University
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-9069
• DOI: 10.1126/science.adf3727
• 发表日期: 2023-03-24
• 关键词: quillaja-saponaria; diversification; identification; spectrometry; expression; pathogens; reductase

摘要

The Chilean soapbark tree (Quillaja saponaria) produces soap-like molecules called QS saponins that are important vaccine adjuvants. These highly valuable compounds are sourced by extraction from the bark, and their biosynthetic pathway is unknown. Here, we sequenced the Q. saponaria genome. Through genome mining and combinatorial expression in tobacco, we identified 16 pathway enzymes that together enable the production of advanced QS pathway intermediates that represent a bridgehead for adjuvant bioengineering. We further identified the enzymes needed to make QS-7, a saponin with excellent therapeutic properties and low toxicity that is present in low abundance in Q. saponaria bark extract. Our results enable the production of Q. saponaria vaccine adjuvants in tobacco and open the way for new routes to access and engineer natural and new-to-nature immunostimulants.