Dr. Thu-Thuy Dang

Scientists at the University of British Columbia Okanagan have identified the specific molecular process plants use to create mitraphylline, a rare natural compound known for its potential anti-tumor and anti-inflammatory properties. The research, which clarifies how plants assemble the molecule’s complex architecture, offers a path toward the sustainable production of substances that currently exist only in trace amounts in the wild.

The Molecular Mechanics of Spirooxindole Alkaloids

Mitraphylline belongs to a specific class of plant chemicals known as spirooxindole alkaloids. These molecules are defined by their distinctive twisted ring structures, a characteristic that contributes to their powerful biological effects. While the value of these compounds has been recognized by the scientific community for years, the exact biological steps required to assemble them remained a mystery.

The research team, working within the Irving K. Barber Faculty of Science, determined that the production of mitraphylline relies on a two-step enzymatic process. Building on previous work from 2023, which identified the first known plant enzyme capable of creating the signature spiro shape, the new study led by doctoral student Tuan-Anh Nguyen pinpointed two critical enzymes. One enzyme is responsible for arranging the molecule into its correct three-dimensional structure, while a second enzyme performs the final twist that completes the molecule.

This biological mechanism allows plants to construct highly complex, non-linear shapes that are often difficult for chemists to replicate in a laboratory setting. By understanding these specific enzymatic roles, researchers can better understand the chemical pathways used by tropical flora to produce potent biological agents.

Addressing Scarcity in Tropical Plant Species

Currently, mitraphylline is found only in extremely small quantities in specific tropical plants, such as kratom (*Mitragyna*) and cat’s claw (*Uncaria*). Because the compound appears in such trace amounts, extracting it from natural sources is often viewed as expensive or impractical for large-scale medical use. This scarcity has historically limited the ability of researchers to utilize the compound’s anti-cancer potential in widespread clinical applications.

The decoding of the plant’s chemical recipe changes the outlook for the compound’s availability. Instead of relying on the harvesting of tropical trees, the identification of the enzymes involved suggests that the process could eventually be replicated through synthetic or biotechnological means. This transition from extraction to production could provide a more stable and sustainable supply of mitraphylline and related spirooxindole alkaloids.

Mapping the Biological Assembly Line

The discovery provides a clearer view of how nature functions as a highly organized chemist. By identifying the enzymes that act as the builders of these molecules, the UBC Okanagan team has effectively mapped the production line of a complex natural product.

This is similar to finding the missing links in an assembly line. It answers a long-standing question about how nature builds these complex molecules and gives us a new way to replicate that process.

Dr. Thu-Thuy Dang, Research Chair in Natural Products Biotechnology at UBC Okanagan

The ability to replicate this process is the primary goal for researchers looking to turn these natural discoveries into accessible medicines. The research highlights the untapped medical potential of plant chemistry, suggesting that many other complex molecules may follow similar, yet-to-be-discovered enzymatic pathways.

As research continues, the focus will likely shift toward how these identified enzymes can be utilized in controlled environments to synthesize mitraphylline. This would bypass the logistical and environmental challenges associated with harvesting rare tropical plants, moving the compound closer to potential use in anti-tumor and anti-inflammatory treatments.