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The complex biochemistry that sees coca plants make cocaine has been unpicked and replicated in a relative of the tobacco plant. Recreating the process by modifying other plants or microorganisms could lead to a way to manufacture the stimulant or produce chemically similar compounds with unique properties.

Biochemists have tried to map out how cocaine is made by the coca plant for more than a century, both because of its unique structure and for its uses in medicine, most recently . Much of this process had been identified, but there was still a missing link between cocaine and a chemical precursor called MPOA.

Now, at the Kunming Institute of Botany in China and his colleagues have found how to bridge this final gap by adding two previously missing enzymes during the process, known as EnCYP81AN15 and EnMT4.

Huang and his team then genetically modified a close relative of the tobacco plant, Nicotiana benthamiana, to produce cocaine using these two enzymes and found it could produce about 400 nanograms of cocaine per milligram of dried leaf, about a 25th of the level in a coca plant.

鈥淎t present, the available production of cocaine in tobacco is not enough to meet the demand on a mass scale,鈥� says Huang, but the constructed biosynthetic pathway could be assembled in organisms with large biomass and quick growth, such as the bacterium Escherichia coli or the yeast Saccharomyces cerevisiae, he says.

The demonstration of cocaine production in tobacco is an important proof of concept, says at the University of York, UK. Transferring this mechanism to other microorganisms could have significant impacts on the supply of cocaine for research purposes. 鈥淚t may allow pharmaceutical companies to ferment it, essentially, and so completely get rid of plant-based production. That will have huge impacts on supply chain and potentially impacts on, even, illicit production.鈥�

But using other plants to produce cocaine won鈥檛 offer an advantage for illicit producers, says Lichman. Growing and harvesting coca, and purifying cocaine from naturally productive plant tissue, is orders of magnitude more scalable and cheaper than producing it in another plant, he says, but having the biosynthetic pathway mapped out could lead to the production of chemically similar compounds to cocaine that have unique medicinal properties.