New chapter in natural product science: how plants craft mitraphylline
Researchers at the University of British Columbia Okanagan have unveiled the plant-based blueprint for mitraphylline, a rare natural compound in the spirooxindole family with potential cancer-fighting properties. This discovery not only answers a long-standing question about how plants assemble these complex molecules but also offers a practical route to producing them more sustainably.
The background: what is mitraphylline and why does it matter?
Mitraphylline is part of a small but powerful class of plant molecules known as spirooxindole alkaloids. These compounds feature unusual twisted ring structures that endow them with strong biological activities, including anti-inflammatory effects and tumour suppression. However, until recently, scientists did not know the exact enzymatic steps plants use to twist and arrange these molecules into their distinctive spiro shapes.
From mystery to mechanism: the enzymes behind the twist
The breakthrough came in 2023 when Dr. Thu-Thuy Dang’s team at UBC Okanagan identified the first plant enzyme capable of twisting a molecule into a spirooxindole configuration. Building on that work, doctoral student Tuan-Anh Nguyen and colleagues identified a pair of enzymes that drive mitraphylline formation. One enzyme sets up the three-dimensional framework of the molecule, while the other enzyme performs the crucial spiro-twist that yields mitraphylline itself.
A new assembly-line analogy
“This is similar to finding the missing links in an assembly line,” says Dr. Dang, who holds the Principal’s Research Chair in Natural Products Biotechnology. “It answers a long-standing question about how nature builds these complex molecules and gives us a new way to replicate that process.”
Why this discovery matters for science and medicine
Natural compounds like mitraphylline often occur in only trace amounts in the plants that produce them. That makes laboratory synthesis or extraction costly and inefficient. By pinpointing the two key enzymes responsible for constructing mitraphylline, researchers now have a roadmap for sustainable production. This could enable broader access to spirooxindole alkaloids for pharmaceutical development, potentially accelerating research into cancer therapies and anti-inflammatory drugs.
A green chemistry path forward
“With this discovery, we have a green chemistry approach to accessing compounds with enormous pharmaceutical value,” says Nguyen. The work demonstrates how a deeper understanding of plant biochemistry can translate into practical strategies for producing complex natural products without depleting natural resources.
Collaboration and support: a North American research effort
The study represents a collaboration between Dr. Dang’s lab at UBC Okanagan and Dr. Satya Nadakuduti’s team at the University of Florida. It was funded by Canadian and American agencies, 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, with support from the United States Department of Agriculture’s National Institute of Food and Agriculture. Dr. Dang emphasizes the value of these partnerships: “Plants are fantastic natural chemists.”
What’s next for the research?
Researchers aim to adapt the enzymes’ molecular tools to create a wider range of therapeutic compounds beyond mitraphylline. The goal is to develop sustainable production platforms for spirooxindole alkaloids, expanding access to potential cancer-fighting drugs and other medicines while reducing reliance on scarce plant material.
In the coming years, the team hopes to scale up these biocatalytic processes and explore how engineered microorganisms or cell-free systems can efficiently manufacture mitraphylline and related molecules at industrial scales.
