Researchers at UBC Okanagan have solved a decades-old puzzle about how plants manufacture mitraphylline, a rare compound showing promise as a cancer fighter. The breakthrough identifies the enzymes responsible for building this complex molecule, opening the door to producing it sustainably outside of nature.
Mitraphylline belongs to a class of plant chemicals called spirooxindole alkaloids, recognized for their twisted ring structures and biological powers, including anti-inflammatory and tumor-suppressing effects. Scientists have long known these compounds exist, but the precise molecular steps plants use to construct them remained a mystery until now.
The breakthrough began in 2023 when Dr. Thu-Thuy Dang's team identified the first known plant enzyme capable of twisting a molecule into the distinctive spiral shape. Building on that work, doctoral student Tuan-Anh Nguyen discovered two additional critical enzymes involved in mitraphylline production. One enzyme organizes the molecule into the correct three-dimensional structure. The second transforms it into mitraphylline itself.
"This is similar to finding the missing links in an assembly line," Dang said. "It answers a long-standing question about how nature builds these complex molecules and gives us a new way to replicate that process."
The discovery carries significant pharmaceutical weight because mitraphylline exists only in trace amounts in tropical plants such as kratom and cat's claw, both members of the coffee family. Extracting meaningful quantities from nature is expensive and inefficient. Now that researchers have mapped the enzymes responsible for creating the compound, they can potentially produce it through biotechnology, dramatically reducing cost and environmental impact.
"With this discovery, we have a green chemistry approach to accessing compounds with enormous pharmaceutical value," Nguyen said. "This is a result of UBC Okanagan's research environment, where students and faculty work closely to solve problems with global reach."
The research combined forces between Dang's laboratory at UBC Okanagan and Dr. Satya Nadakuduti's group at the University of Florida. Funding came from Canada's Natural Sciences and Engineering Research Council, the Canada Foundation for Innovation, the Michael Smith Health Research BC Scholar Program, and the U.S. Department of Agriculture's National Institute of Food and Agriculture.
The next phase will focus on adapting these molecular tools to manufacture a broader range of therapeutic compounds. Dang emphasized that the work represents a new way of thinking about pharmaceutical development. "Plants are fantastic natural chemists," she noted. "Our next steps will focus on adapting their molecular tools to create a wider range of therapeutic compounds."
Author Jessica Williams: "Cracking nature's chemistry recipes could transform drug development, but the real payoff depends on whether biotech companies actually bring these compounds to patients and patients actually benefit."
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