By Timothy S. Donahue

Top Takeaways:

• Major discovery: Researchers identified the missing genes and enzymes that tobacco plants use to produce nicotine.
• Biotech potential: The breakthrough could help scientists develop low-nicotine tobacco plants for pharmaceutical use.
• Long-running mystery: Researchers say the question of how nicotine forms in tobacco plants dates back nearly 200 years.

After nearly two centuries of questions, scientists say they have finally solved how tobacco plants naturally make nicotine.

Researchers from the University of York and the University of Copenhagen identified the missing genes and enzymes responsible for nicotine biosynthesis in tobacco plants, a breakthrough published in the journal Nature Communications.

The discovery could have major implications beyond cigarettes, particularly for pharmaceutical manufacturing and biotechnology using tobacco plants.

“The puzzle of how tobacco plants produce nicotine has been around since the late 1820s, when nicotine was first extracted from the plants,” said Dr. Benjamin Lichman from York’s Centre for Novel Agricultural Products. “Since then no-one had cracked the mystery of how it was made. It is a big moment in plant science and biochemistry that we now have the answer we have been chasing for more than 200 years.”

Scientists have long understood parts of the nicotine pathway but had never fully identified the final steps tobacco plants use to assemble the molecule. The research team reports that it discovered two critical enzymes — NaGR and NicGS — that help synthesize nicotine from smaller molecular components within the plant.

Researchers also found that nicotine is initially formed attached to a glucose molecule, which appears to provide the energy needed for the reaction and then disappears during the final stages of nicotine formation.

That hidden glucose step, researchers say, helps explain why the process remained unsolved for so long. The study focused on Nicotiana tabacum, the primary commercial tobacco species worldwide. But researchers say the implications extend well beyond conventional tobacco products.

“Tobacco plants can be used in biotechnology as platforms for producing vaccines or other pharmaceutical products, but it is plagued by the presence of nicotine which contaminates the products and requires processing to remove it,” Lichman said.

A related species, Nicotiana benthamiana, is already widely used in “molecular farming” to produce vaccines, antibodies, and other pharmaceuticals. Scientists say understanding nicotine biosynthesis could enable researchers to engineer tobacco plants that produce less nicotine while improving efficiency in pharmaceutical production.

“With this new knowledge we can remove or repurpose the nicotine that is produced naturally by the plant and create better biotechnology tools,” Lichman said. “There is also exciting potential for the future to adapt tobacco’s nicotine forming system to make useful pharmaceutical compounds.”

For the nicotine and tobacco industry, the findings also highlight that tobacco research increasingly extends beyond traditional combustible products into biotechnology, pharmaceuticals, and advanced agricultural science.

The discovery may not change cigarettes overnight. But it fundamentally changes scientists’ understanding of one of tobacco’s most significant molecules.