Scientists unlock how plants create cancer-fighting mitraphylline
In a breakthrough that could transform how powerful natural products are sourced, researchers at the University of British Columbia (UBC) Okanagan have mapped the enzymes that make mitraphylline, a rare spirooxindole alkaloid with potential anti-cancer properties. The discovery builds on a landmark finding from 2023 and opens the door to greener, more scalable production of this promising compound.
Mitraphylline sits in a small family of plant molecules known for their distinctive twisted ring structures and potent biological activity. Spirooxindole alkaloids, the broader group to which mitraphylline belongs, have drawn attention for their tumor-fighting and anti-inflammatory effects. Yet for years, the molecular steps that plants use to assemble these complex molecules remained a mystery.
The turning point came when Dr. Thu-Thuy Dang and her team identified the first plant enzyme capable of twisting a molecule into the characteristic spiro shape. Building on that progress, doctoral student Tuan-Anh Nguyen led efforts to identify a pair of enzymes that choreograph the final steps to mitraphylline itself. The discovery mirrors finding missing links in an assembly line, according to Dr. Dang, who is the Principal’s Research Chair in Natural Products Biotechnology at UBC Okanagan.
How the enzymes work together to form mitraphylline
The researchers uncovered two key enzymes involved in mitraphylline biosynthesis. One enzyme helps arrange the molecules into the three-dimensional configuration required for the spiro ring. A second enzyme then twists and connects the structure to yield mitraphylline. This tandem action explains how the plant converts simple starting materials into a highly specific, biologically active compound.
Professor Dang emphasizes that this is not just an academic milestone. “This is similar to finding the missing links in an assembly line,” she says. “It answers a long-standing question about how nature builds these complex molecules and gives us a new way to replicate that process.” The ability to reproduce mitraphylline without harvesting rare tropical trees has important implications for sustainability and drug development.
The value of a sustainable approach to natural products
Natural compounds like mitraphylline are often present in very small quantities in plants, which makes lab-based production expensive or impractical. Mitragyna (kratom) and Uncaria (cat’s claw)—members of the coffee family from which mitraphylline can be sourced—illustrate the challenge: trace amounts in nature demand creative solutions for medical research and potential therapies. By identifying the precise enzymes that assemble and reshape these molecules, the team provides a blueprint for producing mitraphylline and related spirooxindoles in a sustainable, scalable way.
Nguyen notes the broader potential: “With this discovery, we have a green chemistry approach to accessing compounds with enormous pharmaceutical value.” The achievement also reflects the collaborative spirit of modern science. The work stems from a partnership between Dr. Dang’s lab at UBC Okanagan and Dr. Satya Nadakuduti’s team at the University of Florida, combining expertise in natural product chemistry and biotechnological production.
From Canada to the world: funding and future directions
The project benefited from a robust slate of supporters, including Canada’s Natural Sciences and Engineering Research Council’s Alliance International Collaboration program, the Canada Foundation for Innovation, and the Michael Smith Health Research BC Scholar Program. The U.S. National Institute of Food and Agriculture through the USDA contributed resources as well, highlighting cross-border cooperation in addressing global health challenges.
Looking ahead, the researchers aim to adapt the plant-derived enzymatic toolkit to a wider range of therapeutic compounds. “Our next steps will focus on adapting their molecular tools to create a wider range of therapeutic compounds,” says Dang. The team envisions a future where sustainable production of complex natural products becomes routine, enabling faster development of cancer therapeutics and other medicines without depleting natural plant sources.
Impact on science and medicine
This discovery adds a critical piece to the puzzle of natural product biosynthesis. By revealing how a rare molecule like mitraphylline is assembled in nature, scientists gain a powerful template for engineering biosynthetic pathways in microbes or other hosts. The approach aligns with the growing field of green chemistry, reducing reliance on limited plant resources while expanding access to potentially life-saving compounds.
In summary, the identification of the enzymes behind spirooxindole formation marks a significant advance in plant biotechnology and pharmaceutical science. It demonstrates how detailed biochemical understanding can translate into practical strategies for sustainable drug development—and it reaffirms the ingenuity of plants as remarkable chemists.
