Researchers at the University of British Columbia’s Okanagan campus have made a significant breakthrough in understanding how plants produce mitraphylline, a rare natural compound known for its potential anti-cancer properties. This discovery, announced on December 27, 2023, could pave the way for more sustainable production of mitraphylline and related compounds, offering new hope in the fight against cancer.
The team identified two crucial enzymes responsible for shaping and twisting molecules into their final form, solving a long-standing mystery that had puzzled scientists for years. This advancement underscores the remarkable chemical capabilities of plants and their untapped potential in medical research.
Decoding the Complex Chemistry of Mitraphylline
Mitraphylline belongs to a unique family of plant chemicals known as spirooxindole alkaloids. These compounds are distinguished by their twisted ring structures, which contribute to their potent biological effects, including anti-tumor and anti-inflammatory properties. Despite their known value, the precise molecular assembly of these compounds in plants had remained elusive until now.
Progress came in 2023 when a research team led by Dr. Thu-Thuy Dang at UBC Okanagan’s Irving K. Barber Faculty of Science identified the first known plant enzyme capable of creating the spiro shape characteristic of 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 its correct three-dimensional structure and another that finalizes its 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.’
The Challenge of Obtaining Mitraphylline
Many promising natural compounds are found only in trace amounts within plants, making them difficult and costly to produce using traditional laboratory methods. Mitraphylline is one such compound, appearing only in small quantities in tropical trees like Mitragyna and Uncaria, both members of the coffee plant family.
By identifying the enzymes that construct and shape mitraphylline, scientists now have a blueprint for recreating this process in a more sustainable and scalable manner. This discovery could revolutionize how these valuable compounds are produced, reducing reliance on scarce natural sources.
Toward Sustainable Drug Production
Nguyen highlights the broader implications of this research, stating, ‘With this discovery, we have a green chemistry approach to accessing compounds with enormous pharmaceutical value. This is a result of UBC Okanagan’s research environment, where students and faculty work closely to solve problems with global reach.’
He also reflects on the personal significance of the work: ‘Being part of the team that uncovered the enzymes behind spirooxindole compounds has been amazing. 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
The 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 several organizations, 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.’
This breakthrough not only enhances our understanding of plant chemistry but also opens new avenues for the development of sustainable pharmaceuticals. As researchers continue to explore the potential of plant-derived compounds, the implications for medicine and environmental sustainability are profound.
