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 Water forms 'spine of hydration' around DNA, group finds
26.05.2017 | Cornell University

nachricht How herpesviruses win the footrace against the immune system
26.05.2017 | Helmholtz-Zentrum für Infektionsforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Can the immune system be boosted against Staphylococcus aureus by delivery of messenger RNA?

Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.

Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....

Im Focus: A quantum walk of photons

Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.

The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

Im Focus: World's thinnest hologram paves path to new 3-D world

Nano-hologram paves way for integration of 3-D holography into everyday electronics

An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

 
Latest News

How herpesviruses win the footrace against the immune system

26.05.2017 | Life Sciences

Water forms 'spine of hydration' around DNA, group finds

26.05.2017 | Life Sciences

First Juno science results supported by University of Leicester's Jupiter 'forecast'

26.05.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>