In a groundbreaking discovery, researchers at UBC Okanagan have successfully uncovered the process by which plants produce mitraphylline, a rare compound with significant anti-cancer potential. This revelation, announced on December 27, 2023, promises to revolutionize the sustainable production of mitraphylline and similar compounds, highlighting the untapped potential of plants as natural chemists.
The research team identified two critical enzymes responsible for shaping and twisting molecules into their final, biologically active form. This marks a significant advancement in understanding how plants synthesize spirooxindole alkaloids, a small family of plant chemicals known for their distinctive twisted ring structures that contribute to their powerful biological effects, including anti-tumor and anti-inflammatory activities.
Solving a Long-Standing Biological Mystery
The breakthrough came in 2023 when Dr. Thu-Thuy Dang and her team at UBC Okanagan’s Irving K Barber Faculty of Science identified the first known plant enzyme capable of creating the signature spiro shape found in these molecules. Building on this discovery, doctoral student Tuan-Anh Nguyen pinpointed two key enzymes involved in the production of mitraphylline: one that arranges the molecule into the correct three-dimensional structure and another that twists it into its final form.
‘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.’
Why Mitraphylline Is So Hard to Obtain
Mitraphylline is notoriously difficult to obtain due to its presence in only trace amounts in certain tropical trees, such as Mitragyna (kratom) and Uncaria (cat’s claw), both members of the coffee plant family. These trees produce the compound in minute quantities, making traditional laboratory methods of production expensive and impractical.
By identifying the enzymes responsible for constructing and shaping mitraphylline, scientists now have a blueprint for recreating this process in more sustainable and scalable ways. This discovery could pave the way for greener drug production methods, reducing reliance on scarce natural resources.
Toward Greener Drug Production
Nguyen emphasized the significance of the discovery, stating, ‘With this discovery, we have a green chemistry approach to accessing compounds with enormous pharmaceutical value.’ He credited UBC Okanagan’s collaborative research environment for the success of the project, highlighting the close cooperation between students and faculty in tackling problems with global implications.
‘Being part of the team that uncovered the enzymes behind spirooxindole compounds has been amazing,’ Nguyen says. ‘UBC Okanagan’s mentorship and support made this possible, and I’m excited to keep growing as a researcher here in Canada.’
Global Collaboration and Future Directions
This project was a collaborative effort between Dr. Dang’s laboratory at UBC Okanagan and Dr. Satya Nadakuduti’s team at the University of Florida. Funding was provided by multiple sources, 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. Additional support 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.’
The implications of this discovery are vast, offering new avenues for the development of plant-based pharmaceuticals and highlighting the potential of harnessing nature’s own processes for medical advancements. As researchers continue to explore the capabilities of plant chemistry, the future of sustainable drug production looks promising.
