By identifying enzymes that build and shape mitraphylline, researchers now have a roadmap for producing it and related compounds in sustainable ways.
Scientists have made a groundbreaking discovery, uncovering how plants produce mitraphylline, a rare, potent anti-tumour and anti-cancer compound. This breakthrough enables lab-based replication of the molecule, facilitating large-scale production for medical use.
A collaborative team from UBC Okanagan and the University of Florida identified the enzymes and chemical pathways involved in mitraphylline synthesis. This allows researchers to recreate the compound in controlled settings, speeding up pharmaceutical development and reducing dependence on scarce natural sources.
Mitraphylline, a spirooxindole alkaloid, is part of a unique group of plant-derived compounds known for their distinctive ring-shaped structures and therapeutic potential, including anti-inflammatory and immune-boosting effects, with significant promise in cancer treatment.
These compounds have unusual “twisted” ring structures and are known for their strong effects, like fighting tumours and inflammation.
Despite their promise, the molecular process that plants use to make spirooxindoles remained a mystery.
That changed in 2023, when Dr. Thu-Thuy Dang’s research group in the Irving K. Barber Faculty of Science found the first plant enzyme that can twist a molecule into the spiro shape.
“This is similar to finding the missing links in an assembly line,” says Dr. Dang, UBC Okanagan 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.”
Building on that breakthrough, doctoral student Tuan-Anh Nguyen led the effort to identify a pair of enzymes—one that sets up the molecules’ 3D configuration and another that twists it into mitraphylline.
Roadmap for Producing Mitraphylline
Natural compounds are often found in very small amounts in plants, making them difficult or costly to reproduce in the lab. Mitraphylline is one such example: it occurs only in trace amounts in tropical trees like Mitragyna (kratom) and Uncaria (cat’s claw), members of the coffee family.
By identifying enzymes that build and shape mitraphylline, researchers now have a roadmap for producing it and related compounds in sustainable ways.
“With this discovery, we have a green chemistry approach to accessing compounds with enormous pharmaceutical value,” says Nguyen. “This is a result of UBC Okanagan’s research environment, where students and faculty work closely to solve problems with global reach.
“Being part of the team that uncovered the enzymes behind spirooxindole compounds has been amazing,” he adds. “UBC Okanagan’s mentorship and support made this possible, and I’m excited to keep growing as a researcher here in Canada.”
The project is the result of collaboration between Dr. Dang’s lab at UBC Okanagan and Dr. Satya Nadakuduti’s team at the University of Florida.
The work was supported by 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. Support also came from the United States Department of Agriculture’s National Institute of Food and Agriculture.
“We are proud of this discovery coming from UBC Okanagan. Plants are fantastic natural chemists,” Dr. Dang says. “Our next steps will focus on adapting their molecular tools to create a wider range of therapeutic compounds.”
