Main step in the production of cocaine in plants have been unveiled; Research

Scientists have discovered the most significant step in the development of cocaine in the coca plants.

This research has been published online in the June 4 issue of the journal Proceedings of the National Academy of Sciences (PNAS).

Scientists worked on to find the mechanism behind the development of cocaine in the coca plants, so that the medical science will be able to develop new anesthetic drugs without addictive properties.

“Plants can’t run away, so they have to be the planet’s best chemists to survive,” said study co-author John D’Auria, a biochemist at the Max Planck Institute for Chemical Ecology in Germany.

“They make chemicals other organisms simply cannot make, including cocaine.”

[hana-code-insert name=’StumbleUpon’ /][hana-code-insert name=’Reddit’ /]However, to enhance the advantages of the chemicals to humans, he said, “we need to have some idea how the plants are making it. If you understand the biochemistry, you might take away the bad properties and keep the anesthetic ones.”

Scientists in this study worked on legally grown family of flowering plants called Solanaceae, which is also known as the potato or nightshade family, as they have the ability to produce tropane alkaloids. They found that coca plants use different enzymes than Solanaceae plants to produce tropane alkaloid molecules.

“Another thing is that the roots of Solanaceae make tropane alkaloids. Coca does it in the leaves, which is a huge difference,” D’Auria said. “That means nature has found two very different ways to make very similar compounds, which I think is extremely impressive.”

Scientists found an enzyme and the gene responsible for it by moving backward in the chemical reactions while breaking down the finished molecule. This enzyme is responsible for developing the main ring of the cocaine by merging it with benzoic acid, which is considered as the plant’s main step in building the drug.

Abstract for the study is as follows;

The pharmacologically important tropane alkaloids have a scattered distribution among angiosperm families, like many other groups of secondary metabolites. To determine whether tropane alkaloids have evolved repeatedly in different lineages or arise from an ancestral pathway that has been lost in most lines, we investigated the tropinone-reduction step of their biosynthesis. In species of the Solanaceae, which produce compounds such as atropine and scopolamine, this reaction is known to be catalyzed by enzymes of the short-chain dehydrogenase/reductase family. However, in Erythroxylum coca(Erythroxylaceae), which accumulates cocaine and other tropane alkaloids, no proteins of the short-chain dehydrogenase/reductase family were found that could catalyze this reaction. Instead, purification of E. coca tropinone-reduction activity and cloning of the corresponding gene revealed that a protein of the aldo-keto reductase family carries out this reaction in E. coca. This protein, designated methylecgonone reductase, converts methylecgonone to methylecgonine, the penultimate step in cocaine biosynthesis. The protein has highest sequence similarity to other aldo-keto reductases, such as chalcone reductase, an enzyme of flavonoid biosynthesis, and codeinone reductase, an enzyme of morphine alkaloid biosynthesis. Methylecgonone reductase reduces methylecgonone (2-carbomethoxy-3-tropinone) stereospecifically to 2-carbomethoxy-3β-tropine (methylecgonine), and has its highest activity, protein level, and gene transcript level in young, expanding leaves of E. coca. This enzyme is not found at all in root tissues, which are the site of tropane alkaloid biosynthesis in the Solanaceae. This evidence supports the theory that the ability to produce tropane alkaloids has arisen more than once during the evolution of the angiosperms.

Via: National Geographic

Reference:

Jan Jirschitzka, Gregor W. Schmidt, Michael Reichelt, Bernd Schneider, Jonathan Gershenzon, and John Charles D’Auria, (2012). Plant tropane alkaloid biosynthesis evolved independently in the Solanaceae and Erythroxylaceae. PNAS, doi: 10.1073/pnas.1200473109