The plant chemist’s superpower
Plants are nature’s most versatile chemists. Fueled by sunlight and carbon dioxide, they synthesize a dazzling array of natural products that remain challenging to replicate in the lab. In recent work led by Professor Anne Osbourn FRS at the John Innes Centre, researchers harness genomic data, AI, and biotechnology to glimpse a future where drug and natural product discovery can move at plant-like speed.
New insights into how plants harness the sun’s energy to assemble complex molecules are reshaping our approach to medicine and agriculture. The recent study, published in Nature Chemical Biology, centers on triterpenes—one of the largest and most structurally intricate families of plant natural products. These compounds defend plants against pests, influence root microbiomes, and can impact crop quality, all while offering a treasure trove of bioactive molecules with medical and commercial potential.
What are triterpenes and why do they matter?
Triterpenes start from the same basic molecular building block and diversify through the actions of enzymes known as oxidosqualene cyclases (OSCs). These enzymes sculpt and fold the starting molecule, a process likened to chemical origami, generating a vast landscape of shapes and functions. Despite their importance, only a fraction of OSCs have been studied in action, leaving much “dark matter” in plant genomes to explore.
The Osbourn group’s breakthrough
To illuminate this enzymatic diversity, the team systematically mined genomic data from 599 plants, representing nearly 400 species. From an initial pool of about 1,400 OSC gene sequences, they selected 20 candidates for functional validation. These 20 genes were synthesized and introduced into a wild relative of cultivated tobacco that serves as a high-yield, plant-based transient expression system. This approach circumvents the need to source material from wild plant species and enables rapid, scalable testing.
Testing the products of these OSCs yielded several important outcomes. The researchers discovered completely novel chemistries that could serve as drug leads, and they reunited orphan triterpene structures with their parent OSCs. Some findings also opened doors to understanding the evolutionary journeys of OSCs themselves. Dr. Michael Stephenson, joint first author, highlighted that nearly every gene tested produced an interesting result, underscoring the latent potential hidden in plant genomes.
From genomes to molecules at scale
The study demonstrates how computational exploration can accelerate gene discovery—the so‑called “dark matter” of plant genomes—followed by molecular biology and transient expression to produce useful chemistry at scale. As Osbourn notes, we already have genome data for thousands of plant species, and the true potential lies in mining this diversity to find novel structures and functions that synthetic chemistry struggles to replicate.
The implications extend beyond basic science. Industrial partners are being engaged to assess whether the newly discovered chemistries can become drug leads or building blocks for pharmaceutical development. The team also plans to expand the OSC catalogue, broadening the spectrum of enzymes studied and the chemistries accessible through plant biosynthesis.
Practical impact and a future powered by plants
One of the most exciting takeaways is the practical access to highly complex structures that are difficult to produce with conventional chemistry. By leveraging plants as reactors—driven by sunlight and CO2—the path from gene to molecule can be shortened, enabling faster discovery and testing of potential therapies while minimizing reliance on scarce natural materials.
As Stephenson puts it: “We are exploiting the power of plants to make drugs out of sunlight and thin air.” The study not only expands our catalog of OSC functions but also provides a clear framework for translating genomic discoveries into medicinal chemistry and commercial applications.
Looking ahead
The work points to a future where plant genomes guide drug discovery at unprecedented speed. With genome sequencing expanding rapidly, the potential to decode thousands more OSCs grows. The Osbourn group intends to continue building this pipeline, seeking additional OSCs and leveraging partnerships to translate discoveries into lead compounds and scalable production platforms. In a world increasingly focused on sustainable biotechnology, plants’ ability to generate complex, useful chemistry from sunlight represents a promising frontier.
In short, the research illustrates a practical, scalable route to harness the natural power of plants, turning sunlit carbon into a pipeline of drug leads and valuable natural products.
