Researchers Map Toxic Plant Chemistry to Help Develop New Medicines

Unlocking the Chemistry of Wolfsbane and Larkspur

Two famously poisonous plants long studied for their lethal defense mechanisms are yielding secrets that could transform modern pharmacology. Researchers have identified how wolfsbane and larkspur build complex chemical structures that cause paralysis and nerve damage at extremely low doses. While livestock herds in the American West have historically suffered from grazing on wild larkspur, and historical texts mark wolfsbane as a tool for subterfuge, these defensive compounds possess powerful medical potential.

The target of the research group is a class of substances known as diterpenoid alkaloids. These molecules sit at the intersection of two of the oldest and largest groups of plant chemicals on Earth. Their structures are so intricate that despite aconitine being isolated nearly two centuries ago, scientists have never successfully synthesized it in a laboratory.

“These plants have been used in different forms of medicine throughout the world for thousands of years,” said MSU alum Garret Miller, co-first author of the paper and now an assistant professor of biotechnology at the University of Michigan-Flint. “We know they interact with our bodies in so many ways, and understanding how to create them can help provide totally new routes of testing.”

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Garret Miller, assistant professor of biotechnology at the University of Michigan-Flint and MSU alum

A Serendipitous Collaboration in Barcelona

The project gained momentum when Björn Hamberger, study author and the James K. Billman Endowed Professor in MSU’s Department of Biochemistry and Molecular Biology, met members of Tomáš Pluskal’s laboratory at the Czech Academy of Sciences during a research conference in Barcelona. While the Hamberger Lab focused on larkspur, also known as delphinium for its dolphin-shaped flowers, the Pluskal Group was examining the same chemical family in wolfsbane, which is also called monkshood.

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“When this happens, we can either go our own ways, or come together, and it’s joining up that always leads to the best science.”

Björn Hamberger, James K. Billman Endowed Professor at MSU

By combining resources, the international team began tracking thousands of individual genes across multiple species of both plants. Their goal was to pinpoint which genes switched on in specific plant tissues at precise moments to drive the chemical assembly line.

Tracing the Biosynthetic Pathway Inside Tobacco Plants

Plants generally manufacture specialized metabolites slowly and in tiny quantities. To overcome this limitation, the researchers mapped out the multi-step biosynthetic pathway required to construct the diterpenoid alkaloids and transferred those genetic instructions into tobacco plants, which served as living biofactories to test whether the transplanted genes could successfully replicate the natural chemistry.

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“Plants are the best chemists around, upgrading their arsenal of natural compounds over millions of years to help them survive.”

Björn Hamberger, study author

Lana Mutabdžija, a graduate student at the Czech Academy of Sciences and co-first author of the study published in the journal Molecular Plant, noted that everyday molecules such as caffeine, capsaicin, menthol, and vanillin originate from plant chemistry, alongside many frontline medicines.

By turning engineered hosts like yeast or tobacco into biological production systems capable of manufacturing these complex substances in larger quantities, researchers hope to bypass the limitations of harvesting wild plants. The findings provide a foundation for designing new pharmaceutical drugs inspired by natural defense mechanisms.