BEIJING, April 10 (Xinhua) -- For centuries, scientists have known that tobacco plants produce nicotine -- but no one could figure out exactly how they do it. Now, a team of Chinese researchers has finally solved the puzzle.
In a study recently published in the journal Cell, researchers from the Center for Excellence in Molecular Plant Sciences (CEMPS) of the Chinese Academy of Sciences mapped out the complete process -- from start to finish -- of how nicotine is made in a wild species of tobacco called Nicotiana attenuata.
Nicotine is a natural substance belonging to the nightshade family of plants, which includes tomatoes, potatoes and eggplants. It acts as a powerful insect killer, and farmers have used it as a pesticide since the late 1600s. Beyond agriculture, nicotine also shows promise in treating brain-related conditions such as Alzheimer's disease, Parkinson's disease and depression.
To uncover the plant's mechanism for producing nicotine, the researchers used an advanced integrative approach that combines multiple types of biological data, from genes to molecules. Their work led to the identification of a nicotine-free mutant plant, which in turn helped them pinpoint a key gene essential to forming nicotine's core structure.
According to the study, plants do not make nicotine in a single step. Instead, they use a tiny, temporary group of five different enzymes that work together like an assembly line. This group, called a metabolon, carries out a series of carefully coordinated chemical reactions.
Additionally, researchers discovered that plants use a subtle yet sophisticated "glycosylation/deglycosylation" strategy. They rely on this strategy to complete the final coupling reaction that links nicotine's two nitrogen-containing heterocyclic rings. Simply put, the plant attaches a sugar molecule to a reactive intermediate to keep it stable and safe. Then, after a series of reactions -- including reduction, condensation and oxidation -- it removes the sugar to release the final nicotine molecule. This method prevents harmful byproducts from building up inside the plant, solving what the researchers call the "autotoxicity dilemma." In other words, the plant protects itself from being poisoned by its own defensive chemical.
Finally, once nicotine is produced, a specific transporter moves it into a storage compartment within the cell known as the vacuole, where it is kept safely until needed.
"This discovery completes the decades-old puzzle of nicotine biosynthesis," said Li Dapeng, a researcher from the CEMPS.
"Beyond basic science, this work opens the door to using synthetic biology to produce nicotine and other valuable natural compounds in a more efficient and controlled way," Li added. ■
