Researchers at UBC Okanagan have achieved a significant breakthrough by decoding the process through which plants produce mitraphylline, a rare natural compound with promising anti-cancer properties. This discovery, announced on December 27, 2023, in London, UK, could pave the way for sustainable production of mitraphylline and related compounds, offering new avenues for cancer treatment.
Mitraphylline belongs to a unique family of plant chemicals known as spirooxindole alkaloids, characterized by their distinctive twisted ring structures. These molecules are renowned for their potent biological effects, including anti-tumor and anti-inflammatory activities. Despite their known value, the molecular assembly of these compounds in plants remained a mystery until now.
Solving a Long-Standing Biological Mystery
The breakthrough came in 2023 when a team led by Dr. Thu-Thuy Dang from UBC Okanagan’s Irving K Barber Faculty of Science identified the first known plant enzyme capable of forming the spiro shape essential to these molecules. Building on this discovery, doctoral student Tuan-Anh Nguyen identified two crucial enzymes responsible for mitraphylline’s production. One enzyme arranges the molecule into its correct three-dimensional structure, while the other 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.”
Challenges in Obtaining Mitraphylline
Mitraphylline is notoriously difficult to obtain due to its presence in only trace amounts in certain tropical trees like Mitragyna (kratom) and Uncaria (cat’s claw), both part of the coffee plant family. Traditional laboratory methods struggle to produce such compounds economically, making this discovery particularly significant.
By identifying the enzymes involved in mitraphylline’s construction, scientists now have a roadmap for replicating this process sustainably and on a larger scale. This advancement could transform the way pharmaceutical compounds are produced, moving towards greener and more cost-effective methods.
Toward Greener Drug Production
Nguyen highlights the potential impact of this discovery on pharmaceutical production. “With this discovery, we have a green chemistry approach to accessing compounds with enormous pharmaceutical value,” he states. “This is a result of UBC Okanagan’s research environment, where students and faculty work closely to solve problems with global reach.”
Nguyen also shares the personal significance of the research. “Being part of the team that uncovered the enzymes behind spirooxindole compounds has been amazing,” he 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 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.”
The implications of this research extend beyond cancer treatment, potentially revolutionizing the pharmaceutical industry by providing a sustainable method to harness the medicinal properties of plant-derived compounds. As researchers continue to explore the potential of these natural chemists, the future of drug development looks increasingly promising.
