Researchers identify last remaining steps in the biosynthesis of tropane alkaloids from coca

The Institute of Plant Genetics and Crop Plant Research.

Tropane alkaloids are a class of plant-derived compounds that have been used by mankind. The Solanaceae (tomato, tobacco, potato relatives) and the Erythroxylaceae (coca) are the two most studied families. Several tropane alkaloids are listed as some of the most important medicines by the World Health Organization. Cocaine is more notorious for its narcotic and euphorgenic properties.

Dr. John D' Auria is the head of the IPK's research group "Metabolic Diversity."

Solanaceae is the most studied and characterized system for tropane production. There are more than ten chemical modification steps needed to transform the beginning amino acid into the final active alkaloids, and all of these steps have been identified and characterized in solanaceous plants.

Different families may have developed the ability to produce tropanes on their own. Members of the Erythroxylaceae have already been documented to have evolved independently.

The researchers say they have been working on the coca-derived tropane pathway for the last 15 years. The idea that coca would share the same genes was wrong. The pathway leading to the alkaloids is not the same as the final structure.

The lab of Dr. D' Auria collaborated with the lab of Dr. Christina Smolke. Synthetic biology methods are used by the Smolke group to manipulate yeast and other organisms. Their work was published in the journal.

In order to find the missing steps in the coca pathway, we used the multiplicative power of genes in yeast. The researchers reported that they designed and tested multiple candidate sequences.

There were transcriptome studies done in the group of Dr. John D' Auria.

We were able to identify all the missing steps for tropane biosynthesis using this platform. Dr D' Auria says this is the culmination of more than ten graduate student projects in his group.

The most significant part of the findings shows that tropane has evolved at least twice. The researchers say that the study shows that you can mix and match the Solanaceae and Erythroxylaceae genes. Synthetic biologists can use multiple tools to design the tropane alkaloid pathway in organisms that have never produced them before, and with the ability to use different enzymes for similar steps, it is possible to modify those steps for specific chemical outcomes.

Benjamin Chavez is the first author of the study and a student in the D. This sheds light on how plant metabolism can find solutions to problems. We can see the interplay between early precursors and their problems.

The so-called "carbomethoxy group" is only found in coca alkaloids. The solanaceous species don't have this modification. The euphorigenic properties of cocaine are partly responsible for the group of drugs called the carbomethoxy group.

There is more information aboutlucidation of tropane alkaloid in Erythroxylum coca. 10.1073/pnas.

Journal information: Proceedings of the National Academy of Sciences

The Institute of Plant Genetics and Crop Plant Research provided this information.