Technical Articles
Cell Breakthrough | Decoding a 70-Year Mystery: The Complete Biosynthetic Path of Nicotine Revealed, with Inscinstech Protein Purification Equipment Facilitating Top-Journal Research
2026-08-27 14:58
On April 1, 2026, research teams led by Minrui Fan and Dapeng Li from the CAS Center for Excellence in Molecular Plant Sciences at the Chinese Academy of Sciences published a paper titled "Complete biosynthesis of nicotine" in the international top academic journal Cell. For the first time, they completely elucidated the biosynthetic pathway of nicotine, solving a scientific mystery that had puzzled the academic community for over seventy years.
Nicotine is a highly effective insect repellent unique to nightshade plants and is also an important molecule in the study of drugs for mental disorders. Since its first isolation in 1828, the final step of its biosynthesis has remained an unsolved mystery.
Image source：https://www.cell.com/cell/fulltext/S0092-8674(26)00335-1
Major Discovery
The research team identified five key components involved in the final synthesis of nicotine in wild coyote tobacco (Nicotiana attenuata) using information theory-guided cross-scale multi-dimensional omics collaborative analysis techniques:
NaUGT1: Uridine diphosphate glycosyltransferase, catalyzes the glycosylation modification of nicotinic acid
· NaA622: Reductase, responsible for reducing and decarboxylating activating molecules
· NaBBL1/2: Berberine-like bridging enzyme, catalyzes stereoselective intermolecular Mannich reactions
· NaBGL1/2: β-Glucosidase, deglycosylates to produce the final product
· NaMATE1: Transporter, stores nicotine in vacuoles
These five components dynamically assemble into a "metabolon" on the vacuolar membrane of tobacco root cells, functioning like an efficient molecular assembly line to collaboratively complete the synthesis and transport of nicotine.
Protein purification: a crucial step in accurate characterization
To elucidate the molecular mechanism of this metabolic pathway, the research team needs to perform in vitro expression, purification, and enzymatic characterization of the aforementioned key enzymes. High-quality protein purification is fundamental for understanding enzyme catalytic mechanisms and validating metabolic pathways.
During the purification of the NaMATE1 transporter, the research team employed gel filtration chromatography as a sophisticated purification technique. As described in the Methods section of the paper:
After elution, the protein is concentrated and further purified by gel filtration using a Superose 6 Increase column on the protein purification system (Inscinstech Co., Ltd.).
In membrane protein purification, it is necessary to proceed under buffer conditions that maintain protein activity, as any fluctuations in flow rate or pressure changes can affect the separation efficiency and protein yield. Gel filtration chromatography is a separation technique based on molecular size differences and requires high precision and stability of the system's flow rate.
NaMATE1, as a key transporter in the five-component metabolic pathway, is responsible for efficiently transporting synthesized nicotine to vacuoles for storage. The quality of protein purification directly affects subsequent structural analysis and functional validation. This protein can be successfully purified to high purity through gel filtration, demonstrating the reliability and precision of the purification system.
It is worth emphasizing that in the field of membrane protein research, obtaining high-purity, highly active protein samples is often a bottleneck for structural analysis and mechanism studies. The successful purification of NaMATE1 in this study has laid an experimental foundation for further elucidating the working mechanism of metabolic channels.
Academic value and application prospects
This research not only completes the final piece of the nicotine biosynthesis pathway but also reveals the metabolic pathway paradigm of 'synthesis and transport coupling'. The research team successfully reconstructed the nicotine synthesis pathway in heterologous plants such as tomatoes, eggplants, and peas, enabling engineered plants to exhibit significant insect resistance.
This discovery provides a new theoretical basis for breaking through the bottleneck in the biosynthetic efficiency of high-value natural products, and also opens up new directions for the application of synthetic biology in crop improvement.
You can click to view the paper; the link is as follows:https://doi.org/10.1016/j.cell.2026.03.034
Inscinstech specializes in the field of laboratory chromatographic purification, providing reliable protein purification solutions for researchers.
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