Carlos Solis
has been used for millennia, and chemists first isolated from the plant in the late 1820s. Now, 200 years later, biologists report that they have uncovered exactly how the tobacco plant synthesizes the nicotine molecule.
The discovery could change how scientists approach plant-based “molecular farming”—engineering tobacco to produce medicines and vaccines. Nicotine has long been a problem: it causes and contaminates bioproducts, so understanding the pathway will allow researchers to either remove nicotine or redirect its synthesis.
“This is a milestone in plant biology and biochemistry: we finally have the answer people have been searching for for more than 200 years,” says Benjamin Lichman of York University.
How Tobacco Actually Makes Nicotine
Lichman and collaborators at the University of Copenhagen analyzed the genetics of the tobacco plant Nicotiana tabacum. The team found stretches of DNA where genetic elements sit next to—and activate at the same time as—known nicotine-production genes.
The researchers then isolated the enzymes produced by those genes and showed, both in test tubes and in living plants, that those enzymes cooperate to assemble the nicotine molecule.
They found that the pathway runs through a surprising intermediate: a glucose molecule first attaches to the nicotine building blocks. That sugar attachment makes the building blocks reactive and allows them to link together. After assembly finishes, enzymes remove the glucose—the sugar has done its job and is gone. This single-use role for sugar and the plant’s unusual way of using it explain why the mechanism stayed hidden for so long.
The team identified two key enzymes—NaGR and NicGS—that assemble nicotine from raw components: one enzyme uses an amino acid commonly involved in protein synthesis, and the other uses a vitamin-like compound.
Practical implications
The tobacco relative Nicotiana benthamiana is already used in molecular farming to produce life-saving medicines and vaccines. Understanding the nicotine biosynthetic pathway opens the door to using tobacco as a pharmaceutical platform instead of a source of cigarettes.
A separate recent study supports these conclusions: that study shows nicotine forms via a chain of enzymes that involve glucose, and the glucose disappears at the end. This one-time, reversible use of the sugar and its unusual role made the pathway hard to detect.
In the end, the researchers not only solved a 200-year-old mystery but also laid the groundwork for cleaner, more precise use of tobacco in biotechnology. “Tobacco can serve as a platform to produce vaccines and pharmaceutical products, but nicotine undermines that use by contaminating products and forcing extra processing,” Lichman explains.
Based on material from Nature Communications.
Photo: Unsplash
