Scientists at UBC Okanagan have identified the enzymes plants use to produce mitraphylline, a rare compound with potential anti-cancer properties. This breakthrough solves a long-standing mystery and paves the way for sustainable production of such molecules. The discovery highlights plants' untapped potential in medicine.
In a significant advance for natural product research, a team from the University of British Columbia's Okanagan campus has unraveled how plants synthesize mitraphylline, a scarce alkaloid linked to anti-tumor and anti-inflammatory effects. Mitraphylline belongs to the spirooxindole family, characterized by its unique twisted ring structure that contributes to its biological activity.
The journey began in 2023 when Dr. Thu-Thuy Dang's group discovered the first plant enzyme capable of forming the signature spiro shape in these compounds. Building on this, doctoral student Tuan-Anh Nguyen spearheaded the identification of two additional key enzymes: one that organizes the molecule's three-dimensional framework and another that finalizes its twist. "This is similar to finding the missing links in an assembly line," Dr. Dang, UBC Okanagan's Principal's Research Chair in Natural Products Biotechnology, explained. "It answers a long-standing question about how nature builds these complex molecules and gives us a new way to replicate that process."
Mitraphylline occurs in trace amounts in tropical trees such as Mitragyna, known as kratom, and Uncaria, or cat's claw, both from the coffee plant family. This scarcity has historically made it challenging and costly to obtain in quantities suitable for medical research. The new findings provide a blueprint for engineering more efficient production methods, potentially through green chemistry techniques.
"With this discovery, we have a green chemistry approach to accessing compounds with enormous pharmaceutical value," Nguyen noted, crediting UBC Okanagan's collaborative environment. The work involved partnership with Dr. Satya Nadakuduti's laboratory at the University of Florida and was supported by funding from Canada's Natural Sciences and Engineering Research Council, the Canada Foundation for Innovation, Michael Smith Health Research BC, and the US Department of Agriculture.
Looking ahead, Dr. Dang emphasized plants' role as "fantastic natural chemists." The team plans to adapt these enzymatic tools to develop a broader array of therapeutic agents. The research appears in The Plant Cell (2025, volume 37, issue 9).
