A team of scientists has solved the 200-year mystery of how tobacco plants biosynthesize nicotine, identifying the genes and enzymes and demonstrating the process in both the lab and living plants.

Two key enzymes, NaGR and NicGS, were identified as the central catalysts that assemble nicotine from a vitamin-like precursor and an amino acid derivative, with the plant’s metabolism coordinating the two ring structures.

The findings open doors for biotechnology, including reducing or repurposing nicotine production in tobacco and reconfiguring the system to biosynthesize useful pharmaceutical compounds and vaccines via plant molecular farming.

Nicotiana benthamiana, a tobacco relative used in molecular farming, could benefit from the new knowledge by improving safety through reduced nicotine contamination in plant-derived products.

Nature Communications links nicotine formation to a glucose-driven mechanism, showing nicotine is initially formed attached to a glucose molecule, which is removed in the final step.

A related study reinforces that nicotine assembly involves glucose-derived steps with enzyme assistance and that the glucose vanishes after the final synthesis.

The research explains that nicotine is formed through a sequence where glucose attaches to precursors to enable assembly, and then the glucose is released, clarifying why the process was so enigmatic.

Genetic analysis revealed tightly linked genes that activate alongside known nicotine pathway genes, with enzyme roles validated in both test tubes and living plants.

While questions remain, the work asserts that the main steps and components are understood, potentially enabling low-nicotine tobacco varieties without sacrificing plant growth.

Researchers from the University of York and the University of Copenhagen conducted the study, solving a 200-year-old puzzle by pinpointing the responsible genes and enzymes.