Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

How plants make cocaine

06.06.2012
The discovery of the first enzyme in the pathway sheds new light on the evolution of alkaloid formation

Cocaine is one of the most commonly used (and abused) plant-derived drugs in the world, but we have almost no modern information on how plants produce this complex alkaloid.


Coca plant (Erythroxylum coca) and the molecular structure of cocaine (grey: carbon, blue: nitrogen, red: oxygen, white: hydrogen). Max Planck Institute for Chemical Ecology/ D’Auria, Jirschitzka


Immunolabeling (green areas) of MecgoR, the enzyme catalyzing the penultimate step of cocaine biosynthesis. The picture shows the strong accumulation of the enzyme in a cross section of a very young E. coca leaf, which is still curled around the growing stem tip. Bar: 0,1 mm. Max Planck Institute for Chemical Ecology/ D’Auria, Jirschitzka

Researchers from the Max Planck Institute for Chemical Ecology in Jena, Germany, have just discovered a key reaction in cocaine formation in the coca plant from South America, and identified the responsible enzyme. This enzyme was shown to belong to the aldo-keto-reductase protein family revealing some exciting new insights into the evolution of cocaine biosynthesis.

Humans encounter alkaloids every day

Alkaloids constitute a very large group of natural nitrogen-containing compounds with diverse effects on the human organism. A large variety of plant-produced alkaloids have strong pharmacological effects, and are used as toxins, stimulants, pharmaceuticals or recreational drugs, including caffeine, nicotine, morphine, quinine, strychnine, atropine and cocaine. Atropine, used to dilate the pupils of the eye, and the addictive drug cocaine are both tropane alkaloids which possess two distinctive, inter-connecting five- and seven-membered rings.

Plants commonly produce tropane and other alkaloids for protection against herbivores and other enemies. Species in seven plant families are known to produce tropane alkaloids, including the Brassicaceae (mustard family), Solanaceae (nightshade or potato family) and Erythroxylaceae (coca family). These families are not closely related to each other. For example, it is assumed that the last common ancestor of the Erythroxylaceae and the Solanaceae lived about 120 million years ago. But how similar are the tropane alkaloid biosynthetic pathways in these families? Was there a single original tropane alkaloid pathway which was lost in most other plant families during the course of evolution? Or, did tropane alkaloid biosynthesis arise independently on several different occasions?

Atropine and cocaine: Two tropane alkaloids, two plant species, two different enzymes

John D’Auria, project leader in the Department of Biochemistry at the Max Planck Institute for Chemical Ecology, has been studying the coca plant, from which the drug cocaine is derived. Native tribes in South America have been cultivating coca and chewing its leaves for at least 8000 years for their stimulant and hunger-suppressing properties.
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 green organs of the plant. Based on these results, the Max Planck researchers conclude that the tropane alkaloid pathways in coca and belladonna evolved completely independently.
Elucidation of the MecgoR-catalyzed step in cocaine biosynthesis represents a major success, but the researchers are now continuing to investigate other important steps in the cocaine pathway. Also of interest is to learn how cocaine is stored in leaf tissue in such high amounts. This alkaloid can account for up to 10% of the dry weight of the immature coca leaf, a phenomenal amount for the accumulation of any one particular alkaloid. [JWK/AO]

Original publication:

Jan Jirschitzka, Gregor W. Schmidt, Michael Reichelt, Bernd Schneider, Jonathan Gershenzon, John C. D´Auria: Plant tropane alkaloid biosynthesis evolved independently in the Solanaceae and Erythroxylaceae. Proceedings of the National Academy of Sciences USA, Early Edition, June 4, 2012, DOI: 10.1073/pnas.1200473109

Further Information:

Dr. John C. D’Auria, dauria@ice.mpg.de, +49 3641 57 1335

Picture Requests:

Angela Overmeyer M.A., +49 3641 57-2110, overmeyer@ice.mpg.de
or download from http://www.ice.mpg.de/ext/735.html

Dr. Jan-Wolfhard Kellmann | Max-Planck-Institut
Further information:
http://www.ice-mpg.de

More articles from Life Sciences:

nachricht In focus: Peptides, the “little brothers and sisters” of proteins
12.11.2018 | Technische Universität Berlin

nachricht How to produce fluorescent nanoparticles for medical applications in a nuclear reactor
09.11.2018 | Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences (IOCB Prague)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: A Leap Into Quantum Technology

Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.

In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...

Im Focus: Research icebreaker Polarstern begins the Antarctic season

What does it look like below the ice shelf of the calved massive iceberg A68?

On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.

Im Focus: Penn engineers develop ultrathin, ultralight 'nanocardboard'

When choosing materials to make something, trade-offs need to be made between a host of properties, such as thickness, stiffness and weight. Depending on the application in question, finding just the right balance is the difference between success and failure

Now, a team of Penn Engineers has demonstrated a new material they call "nanocardboard," an ultrathin equivalent of corrugated paper cardboard. A square...

Im Focus: Coping with errors in the quantum age

Physicists at ETH Zurich demonstrate how errors that occur during the manipulation of quantum system can be monitored and corrected on the fly

The field of quantum computation has seen tremendous progress in recent years. Bit by bit, quantum devices start to challenge conventional computers, at least...

Im Focus: Nanorobots propel through the eye

Scientists developed specially coated nanometer-sized vehicles that can be actively moved through dense tissue like the vitreous of the eye. So far, the transport of nano-vehicles has only been demonstrated in model systems or biological fluids, but not in real tissue. The work was published in the journal Science Advances and constitutes one step further towards nanorobots becoming minimally-invasive tools for precisely delivering medicine to where it is needed.

Researchers of the “Micro, Nano and Molecular Systems” Lab at the Max Planck Institute for Intelligent Systems in Stuttgart, together with an international...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

“3rd Conference on Laser Polishing – LaP 2018” Attracts International Experts and Users

09.11.2018 | Event News

On the brain’s ability to find the right direction

06.11.2018 | Event News

European Space Talks: Weltraumschrott – eine Gefahr für die Gesellschaft?

23.10.2018 | Event News

 
Latest News

In focus: Peptides, the “little brothers and sisters” of proteins

12.11.2018 | Life Sciences

Materials scientist creates fabric alternative to batteries for wearable devices

12.11.2018 | Materials Sciences

A two-atom quantum duet

12.11.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>