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29th Nov 2022

New tobacco plant produces cocaine inside its leaves in bizarre breakthrough

Steve Hopkins

Scientists have been trying to crack the code for more than a century

In news that may delight drug traffickers, a new genetically modified tobacco plant is reportedly able to produce cocaine inside its leaves.

A study published earlier this month reveals how scientists have managed to recreate the cocaine-producing biochemistry of the coca plant inside the leaves of a tobacco plant relative.

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, New Scientist reported.

Cocaine is naturally produced in the leaves of the Erythroxylum coca plant, but a team of researchers at the Kunming Institute of Botany in China decided to see if they could recreate the process.

Using a relative of the tobacco plant called Nicotiana benthamiana, Sheng-Xiong Huang and his colleagues recreated the unique biochemistry normally found in the coca plant through genetic modification.

The scientists produced two enzymes that generate cocaine when the leaves are dried, known as EnMT4 and EnCYP81AN15.

This meant the tobacco plant could produce methylecgonone – a tropane alkaloid found in coca leaves – on its own.

In the study – published in the Journal of the American Chemical Society and titled ‘Discovery and Engineering of the Cocaine Biosynthetic Pathway’, the authors wrote: “Cocaine, the archetypal tropane alkaloid from the plant genus Erythroxylum, has recently been used clinically as a topical anesthesia of the mucous membranes.

“Despite this, the key biosynthetic step of the requisite tropane skeleton (methylecgonone) from the identified intermediate 4-(1-methyl-2-pyrrolidinyl)-3-oxobutanoic acid (MPOA) has remained, until this point, unknown.

“Herein, we identify two missing enzymes (EnCYP81AN15 and EnMT4) necessary for the biosynthesis of the tropane skeleton in cocaine by transient expression of the candidate genes in Nicotiana benthamiana. Cytochrome P450 EnCYP81AN15 was observed to selectively mediate the oxidative cyclization of S-MPOA to yield the unstable intermediate ecgonone, which was then methylated to form optically active methylecgonone by methyltransferase EnMT4 in Erythroxylum novogranatense.”

Huang’s team reported a “near-complete biosynthetic pathway of cocaine”. The study also provided, “new insights into the metabolic networks of tropane alkaloids (cocaine and hyoscyamine) in plants”.

The findings, the team said, offers “significant implications” for pharmaceutical production.

New Scientist reported that reproducing the entire biochemical pathway in another plant could help people manufacture the drug for scientific study.

Huang explained to the publication: “At present, the available production of cocaine in tobacco is not enough to meet the demand on a mass scale.”

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