28 November 2022

Tobacco instead of coca

Chinese geneticists have created tobacco plants that produce cocaine

Sergey Vasiliev, Naked Science

Cocaine is a dangerous drug that is isolated from coca leaves. At the same time, the set of chemical reactions by which the plant produces it has so far been completely unknown. A team of Chinese scientists from the Kunming Institute of Botany managed to determine the last steps of cocaine biosynthesis, and other "natural producers" of drugs, tobacco plants helped them. An article about this was published in the Journal of the American Chemical Society (Wang et al., Discovery and Engineering of the Cocaine Biosynthetic Pathway).

Back in the distant past, the inhabitants of South America discovered that plants of the genus Erythroxylum produce alkaloids that have a stimulating and narcotic effect. The key of these substances, cocaine was isolated by scientists in the middle of the XIX century. For a long time, it has been widely used as a medical remedy and stimulant, but due to addiction and other negative health consequences, it was included in the list of prohibited substances and became illegal.

Today, cocaine is legally produced in very limited quantities and under the strictest control, exclusively for medical and scientific purposes. There are methods that allow you to synthesize a substance "from scratch" and, of course, extract it from the leaves of a cocaine bush. However, the pathway of cocaine formation in the plants themselves has not yet been fully determined. Previously, it was possible to trace it to an intermediate compound, a derivative of oxybutanoic acid MROA, but the final steps of converting MROA into cocaine remained unclear. It was possible to find out them only now.

At the final stages, MROA molecules must undergo methylation and oxidative cyclization reactions. Therefore, scientists led by Sheng-Xiong Huang (Sheng-Xiong Huang) examined the DNA of the cocaine bush to determine the sites that encode proteins that catalyze the appropriate reactions: methylases and oxidases. They transferred the most promising genes to Bentham tobacco (Nicotiana benthamiana), a popular model organism for studying plant physiology.


Evaluating the performance of various pairs of enzymes, the authors concluded that the most effective combination was EnCYP81AN15 oxidase and EnMT4 methylase. Under the action of the first protein, MROA is cyclized, under the action of the second it attaches a methyl group, leading to the appearance of cocaine. The leaves of such GM tobacco contained up to 400 nanograms of the drug per milligram of dried mass, which is less than five percent of the cocaine bush contained in the leaves.

Now that the complete pathway of cocaine biosynthesis has been established, the corresponding genes can be transferred to bacteria in order to obtain the substance in the quantities necessary for medicine and science. At the same time, scientists emphasize that their work will not bring any benefit to illegal drug-related business. According to them, the production of cocaine in the traditional way, from coca leaves, is much easier and cheaper, and GM bacteria are unlikely to be attractive to drug cartels.

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