Plants as Natural Chemists: Harnessing Sunlight for Drug Discovery
Plants transform light and carbon dioxide into a dazzling array of complex molecules. In a new line of research, scientists are tapping into that natural chemistry to accelerate the discovery of drug leads and valuable natural products. The study, conducted by the group of Professor Anne Osbourn FRS at the John Innes Centre and published in Nature Chemical Biology, investigates the world of triterpenes—one of the most structurally diverse and biologically active families of plant natural products.
Understanding Triterpenes and Oxidosqualene Cyclases (OSCs)
Triterpenes begin from a common starting molecule and diverge into thousands of forms through the action of enzymes called oxidosqualene cyclases (OSCs). These enzymes physically fold and sculpt the molecule, a process likened to chemical origami, generating a wealth of shapes with potential medicinal and agricultural applications. Yet only a fraction of OSCs have been studied in action, leaving a vast landscape of untapped chemistry.
Genome Mining Across Hundreds of Plants
The researchers systematically mined genome sequences from 599 plants, representing nearly 400 species, to identify OSC-encoding genes. From an initial pool of about 1,400 OSC sequences, they selected 20 for functional validation. These 20 genes were synthesized and introduced into a wild relative of cultivated tobacco using a plant-based, high-yield transient expression system. This approach enabled rapid testing of enzyme products without the need to source material from wild species.
Key Findings: Novel Chemistry and Clues to Evolution
Testing the products of these OSC enzymes yielded multiple surprising results. The team discovered completely novel chemistries that could serve as drug leads and reunited several orphan triterpene structures with their parent OSC enzymes. Some products offered actionable clues about the evolutionary journeys of OSCs, revealing how these enzymes diversified to create molecular complexity.
Implications for Drug Discovery and Biotechnology
One of the most exciting outcomes is the demonstration that large-scale gene mining, supported by computational tools, can illuminate the “dark matter” of plant genomes. This accelerates gene discovery and enables subsequent molecular biology and plant-based production to generate useful chemistry at scale for medicine and multiple commercial applications.
Quotes and Perspectives from the Team
Joint first author Dr. Michael Stephenson noted that nearly every gene tested yielded an interesting result, with several paths forward for exploration. He emphasized the safety and practicality of obtaining novel chemistry without collecting material from wild populations. Corresponding author Professor Anne Osbourn highlighted the abundance of plant diversity yet to be explored: there are roughly 450,000 known plant species, and only a fraction have been tapped for useful chemistry.
Future Directions: From Lab to Industry
The team plans to collaborate with industrial partners to assess the discovered chemicals as lead compounds or building blocks for drug development. They also aim to expand the pipeline to identify additional OSCs, broadening the scope of enzyme studies. The work showcases a practical path to accessing highly complex structures that are difficult to obtain through traditional synthesis, leveraging the power of plants to produce drug candidates from sunlight and air.
Concluding Thoughts: A New Era of Plant-Driven Drug Discovery
As plant genomes become more richly annotated and computational methods grow more powerful, the potential to uncover new therapeutics and bioactive compounds from plant roots and leaves accelerates. The Osbourn group’s research offers a tangible glimpse of a future where plant biology and biotechnology collaboratively streamline drug discovery, with implications spanning medicine, agriculture, and industry.
