HudsonAlpha Research Report 2023-2024

ANTI-CANCER COMPOUNDS IN SOAPWORT

The soapbark tree is not the only plant that produces potentially therapeutic

saponins. Saponaria officinalis , commonly known as soapwort, is a perennial flowering plant native to Asia and

Europe. Soapwort extracts have been traditionally used as soap and medicine. Today, they are still used in cosmetic, nutraceutical, and phytomedicinal products. Soapwort saponins have anticancer proper- ties and are also of interest in improving target- ed tumor therapies. The major saponins found in soapwort extracts (saponariosides A and B (SpA and SpB)) are structurally similar to QS-21 in soapbark. Like QS-21, little was known about the biosynthetic pathway that produces SpA and SpB until recently. The same team from the soapbark project, plus members of HudsonAlpha’s Genome Sequencing Center, which is led by HudsonAlpha Faculty Investigators Jane Grimwood, PhD , and Jeremy Schmutz , dove into the genome of soapwort in much the same way as the soapbark tree 2 . Through their analysis, they uncovered the complete biosynthetic pathway to SpB, including 14 genes that support SpB biosynthe- sis. This set of studies underscores the power of genomics-based approaches to uncover com- plex biosynthetic pathways, offering a blueprint for future investigations into pharmaceutically relevant compounds. This innovative platform, integrating genome mining, gene coexpression, and func- tional analysis, empowers researchers to tap into the vast chemical diversity of the plant kingdom. By identifying and engineering novel biosynthetic pathways, they can unlock natural and synthetic compounds with potential appli- cations in medicine, drug delivery, and immu- nology. This groundbreaking approach holds the promise of revolutionizing the discovery and development of life-saving therapeutics. ■

Long before modern soaps, ancient civilizations used plants rich in saponins to cleanse themselves and their textiles.

A collaborative team of scientists, led by John Innes Centre Professor Ann Osborne, PhD, dove into the soapbark tree’s genome to help uncover the biochemical pathway that creates these adjuvant compounds 1 . HudsonAlpha Fac- ulty Investigator Alex Harkess, PhD , and Univer- sity of Georgia Professor of Plant Biology Jim Leebens-Mack, PhD, led parts of the sequencing and analysis efforts. Along with the Osborne group, the team used powerful computation- al gene-mining tools to predict which of the ~30,000 genes in the soapbox tree genome was responsible for saponin biosynthesis. This led to the identification of a biosynthetic pathway of 16 genes, which together produce the enzymes that are nature’s building blocks for saponin production. Discovering the enzymes that create saponins will allow scientists to pro- duce these valuable adjuvants without depleting our soapbark tree populations and design new adjuvants with enhanced properties. The high-quality soapbark tree genome opened the doors to all of these possibilities.

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