Researchers have uncovered the role of the GAME15 protein in the biosynthesis of crucial steroidal compounds in solanaceous plants, paving the way for advancements in pest-resistant crops and medical treatments for cancer.
Researchers at the Max Planck Institute for Chemical Ecology have made a landmark discovery, identifying the GAME15 protein as a key player in the biosynthesis of steroidal compounds in solanaceous plants like potatoes, tomatoes, and eggplants. This breakthrough not only provides insights into plant defense mechanisms but also opens up new avenues for medical and agricultural applications.
“By identifying GAME15, we were able to reconstitute the metabolic pathway for steroidal compounds in heterologous hosts such as Nicotiana benthamiana, up to the scaffold furostanol, a precursor of steroidal saponins, and solasodine, an immediate precursor of steroidal glycoalkaloids,” lead author Prashant Sonawane, who is currently an assistant professor at the University of Missouri, said in a news release.
Understanding GAME15
The research team investigated the wild Solanum nigrum (black nightshade) because of its diverse production of steroidal compounds. These compounds, derived from cholesterol, vary between the plant’s leaves and berries, serving critical roles in both plant defense and potential human health benefits.
By utilizing biochemical and molecular biology techniques, the researchers identified that GAME15 interacts with other vital enzymes — GAME6, GAME8 and GAME11 — responsible for the hydroxylation of cholesterol. This interaction marks the crucial step toward the formation of compounds like steroidal saponins and glycoalkaloids.
Medical and Agricultural Implications
Steroidal saponins and glycoalkaloids have shown promising medical applications, including their potential in treating liver cancer and exhibiting anti-cancer, antimicrobial and anti-inflammatory properties.
The identification of GAME15 enables the reconstitution of these pathways in other plants, a technique known as “pharming,” which could revolutionize the cost-effective production of medicinal compounds.
Ecological Significance
The ecological role of these compounds was also examined.
GAME15 knockout plants, which are unable to produce saponins, were found to be more susceptible to insect herbivores. In experiments involving leaf-feeding trials with the leafhopper Empoasca decipiens and the Colorado potato beetle Leptinotarsa decemlineata, herbivores showed a clear preference for knockout leaves over wild-type leaves.
This discovery sheds light on the importance of saponins in plant defense mechanisms.
“Our discoveries highlight how Solanaceae plants have adapted a cellulose-synthase like protein hijacked from a core metabolism role (such as cellulose biosynthesis) to a structural role, required for the biosynthesis of compounds specialized in the defense of the plants against pathogens,” senior author Sarah O’Connor, a director of the Department of Natural Product Biosynthesis at the Max Planck Institute, said in the news release.
“This discovery opens up new opportunities for engineering crops with enhanced resistance to pests and for the production of important steroid-based compounds to fight cancer and other diseases,” she added.
Conclusion
This groundbreaking research not only elucidates a long-hidden aspect of plant defense but also suggests a future where crops are more resilient to pests, and vital medicinal compounds are produced more efficiently. The study has set the stage for further exploration and potential utilization of steroidal compounds in agriculture and medicine, promising a healthier and more sustainable future.