Researchers have discovered a way to produce cocaine from a tobacco plant

In the 19th century, cocaine was used as effective local anesthesia for eye surgery, solving the dilemma of ocular surgery without anesthetics. More recently, the US Food and Drug Administration (FDA) approved the use of cocaine as a topical anesthesia of mucous membranes.

However, the biosynthetic route through which the coca plant produces cocaine has baffled scientists even after 100 years of investigation. The compound has a complex and unique chemical structure and can stimulate anesthetic activity, making it difficult to replicate its biosynthesis.

Genetic modification

Previously, scientists knew that a chemical precursor called MPOA was converted into cocaine. How its converted was not known until now.

In the new study, Sheng-Xiong Huang and his colleagues at the Kunming Institute of Botany in China have discovered a way to better understand the process by introducing two previously absent enzymes known as EnMT4 and EnCYP81AN15. These enzymes are responsible for converting the chemical precursor into cocaine.

To prove it, researchers genetically modified tobacco's closest relative, the Nicotiana benthamiana, to produce these two enzymes, resulting in the synthesis of cocaine in the plant's leaves. Experiments showed that the modified plant could produce about 400 nanograms of cocaine per milligram of dried leaf or roughly 25% of the amount found in a coca plant.

"Currently, the available production of cocaine in tobacco is not sufficient to meet large-scale demand," explained Sheng-Xiong Huang, a co-author of the study.

Despite the drug's infamy, cocaine is chemically similar to a host of anesthetics and stimulants. Unlocking its biosynthetic pathway will lead to the development of new drugs without the addictive qualities of cocaine.

The team hopes that their research could lead to the modification of other organisms that could produce it on a larger scale, such as bacteria and yeast.

Researchers note that the breakthrough is unlikely to have any impact on the illicit cocaine trade for various reasons. For starters, the study is just a proof of concept. Anyone who wants to replicate the process will need a deep understanding of genetic technology, a lab, and lots of hi-tech equipment.

The cultivation and harvesting of coca, as well as the purification of cocaine from the natural tissues of the plant, are orders of magnitude more scalable and cheaper than genetically modifying other plants to produce cocaine.

The study has been published in the Journal of the American Chemical Society.