Although the formation of cocaine has not been investigated in the last 40 years, the biosynthesis of the related tropane alkaloid, atropine, from belladonna (Solanaceae) is well-established. In the penultimate step, a ketone function is reduced to an alcohol residue. This key reaction is catalyzed by an enzyme of the short-chain dehydrogenase/reductase (SDR) protein family in belladonna. Among this group of enzymes are also many alcohol-degrading dehydrogenases in animals.
To find the corresponding enzyme in cocaine biosynthesis, Jan Jirschitzka, a PhD student in the group, searched the genome of the coca plant to look for SDR-like proteins. However, all the SDR genes that he cloned and expressed did not show any activity for the key reaction in cocaine formation. So he used a more classical approach − identifying the cocaine-synthesizing enzyme activity in extracts from coca leaves, purifying the responsible protein, isolating the polypeptide, and − after partial sequencing − cloning the corresponding gene.
Cocaine in young leaves, atropine in roots
"We obtained two very interesting results," says 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 catalyzed by a completely different enzyme in coca plants as compared to that in the Solanaceae, namely by an aldo-keto reductase (AKR)." The enzyme was named methylecgonone reductase (MecgoR). AKR enzymes are known in plants and also mammals, amphibians, yeast, protozoa, and bacteria. They are involved in the formation of steroid hormones, for example. The second result is that the MecgoR gene, as well as the protein, is highly active in the very young leaves of coca plants, but not in the roots. Atropine, on the other hand, is synthesized exclusively in the roots of belladonna, from where it is transported into the gree
|Contact: John C. D'Auria|
Max Planck Institute for Chemical Ecology