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

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. Saponins, a type of plant-derived glycoside, are useful in formulations including soaps, medicines, and root beer foam. Reed et al. studied how the Chilean soapbark tree (Quillaja saponaria) makes its saponins, which lend immunostimulatory activity to vaccines against shingles, malaria, and COVID-19 (see the Perspective by Chubatsu Nunes and Dang). The saponins are currently extracted from the tree?s bark. The identification of enzymes in the biosynthetic pathway opens doors to the more sustainable production of these useful adjuvants and opportunities to engineer new adjuvants. ?PJH Genome-based pathway discovery reveals the biosynthetic route to vaccine adjuvants produced by the soapbark tree.