16 March 2010

The most important secret of the opium poppy has been solved

Scientists at the University of Calgary (Canada), working under the guidance of Professor Peter Facchini, identified the genes that ensure the ability of this plant to synthesize the alkaloids codeine and thebaine. The results of the work published in the preliminary on-line version of the journal Nature Chemical Biology in the article "Dioxygenases catalyze the O-demethylation steps of morphine biosynthesis in opium poppy" open up new alternative possibilities for the production of effective painkillers using genetically modified microorganisms or plants.

Codeine is by far the most widely used opiate worldwide and one of the most popular painkillers. Codeine can be isolated directly from plants, but its main part is synthesized from morphine contained in opium poppy plants in much larger quantities. In the liver, codeine is converted by a specific enzyme into morphine, which has a pronounced analgesic effect. Codeine addiction is produced much worse than morphine, so it is widely used as an analgesic and antitussive (another morphine derivative, heroin, was also initially sold as a cough remedy).

The alkaloid thebaine is contained in opium poppy in even smaller quantities. Thebaine itself has not found therapeutic use, however, some of its derivatives obtained by chemical synthesis reactions are used as powerful analgesics and in substitution therapy for opiate addiction.

The researchers analyzed about 23,000 opium poppy genes using modern genomics methods, as a result of which they found two genes encoding the enzymes thebaine 6-O-demethylase (T6ODM) and codeine O-demethylase (codeine O-demethylase, CODM), which ensure the conversion of thebaine and codeine morphine.

The authors obtained the final confirmation of the results obtained by suppressing the expression of the identified genes with the help of viral vectors, which stops the process of morphine synthesis in opium poppy plants at the thebaine and codeine stages.

According to Faccini, who has devoted his career to studying the unique properties of the opium poppy, scientists have spent more than 50 years searching for enzymes encoded by two identified genes. Therefore, the detection of not only enzymes, but also the genes encoding them is an important achievement, equivalent to the identification of the gene responsible for the development of a serious disease.

This discovery will allow scientists to create genetically modified opium poppy plants in which the process of synthesizing opiates will stop at codeine or thebaine. In the near future, researchers plan to create genetically modified yeast or bacteria, the use of which in bioreactors in the future will significantly reduce the cost of production of codeine and other opium analgesics used in medicine.

Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on EurekAlert: Unlocking the opium poppy's biggest secret.

16.03.2010


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