Unlocking the blueprint for a powerful plant-based drug

(Press-News.org) Researchers at UBC Okanagan have uncovered how plants produce mitraphylline, a rare natural compound that may help fight cancer. 

Mitraphylline belongs to a small group of plant molecules called spirooxindole alkaloids.  

These compounds have unusual “twisted” ring structures and are known for their strong effects, like fighting tumours and inflammation.  

Despite their promise, the molecular steps 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.  

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. 

“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.” 

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,” Nguyen 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,” she says. “Our next steps will focus on adapting their molecular tools to create a wider range of therapeutic compounds.” 

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