Very little has been known for a long time about the mechanism by which plants produce cocaine, in spite of the fact that it is such a widely used drug. Cocaine is one of the alkaloids, a large group of natural compounds which contain nitrogen and have a range of effects on the human body.
Plant-produced alkaloids such as cocaine, strychnine, atropine, nicotine, caffeine, quinine and morphine have been put to a variety of uses, for example as medical and recreational drugs, toxins and stimulants. Cocaine, like atropine – which is extracted from the plant with the common name ‘belladonna’, of the Solanaceae
family – is a tropane alkaloid.
While the biosynthetic pathway for the formation of atropine in belladonna is known, the mechanism by which cocaine is produced has not been examined in the past 40 years.
A study from the Max Planck Institute for Chemical Ecology in Jena has now come to the conclusion that the alkaloid-forming pathways in the Solanaceae
family and the Erythroxylaceae
family, to which the coca plant belongs, must have evolved independently rather than stemming from a common ancestor as had been hypothesised.
The research group examined the genome of the coca plant (Erythroxylum coca
) in search of an enzyme corresponding to the one which catalyses the penultimate reaction in the synthesis of atropine by Solanaceae
. This enzyme is a member of the short-chain dehydrogenase reductase (SDR) family of proteins.
PhD student Jan Jirschitzka searched for proteins similar to SDR in the coca plant genome, but found nothing which showed any reactivity in the key step for cocaine synthesis. In order to identify it. the protein responsible for catalysing the reaction had to be isolated and sequenced.
"We obtained two very interesting results," explained Jonathan Gershenzon, Director at the institute. "The enzyme reaction analogous to that in atropine synthesis – the conversion of the keto group into an alcohol residue – is catalysed by a completely different enzyme in coca plants as compared to that in the Solanaceae
, namely by an aldo-keto reductase (AKR)."
AKR proteins are involved in making steroid hormones, for example, and are found in mammals, amphibians, bacteria, yeast and protozoa as well as plants. The enzyme was named methylecgonone reductase (MecgoR), and it is particularly active in the young leaves of the coca plant. This is in contrast to belladonna, where atropine is created only in the roots before being transported to other parts of the organism.
Further work is now being carried out on other stages in the cocaine-forming pathway, with the team especially interested in how very high amounts of the alkaloid – up to ten per cent of the dry weight – can be stored in young coca leaves.