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 Lab-free infection test could eliminate guesswork for doctors
26.02.2020 | University of Southampton

nachricht MOF co-catalyst allows selectivity of branched aldehydes of up to 90%
26.02.2020 | National Centre of Competence in Research (NCCR) MARVEL

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: High-pressure scientists in Bayreuth discover promising material for information technology

Researchers at the University of Bayreuth have discovered an unusual material: When cooled down to two degrees Celsius, its crystal structure and electronic properties change abruptly and significantly. In this new state, the distances between iron atoms can be tailored with the help of light beams. This opens up intriguing possibilities for application in the field of information technology. The scientists have presented their discovery in the journal "Angewandte Chemie - International Edition". The new findings are the result of close cooperation with partnering facilities in Augsburg, Dresden, Hamburg, and Moscow.

The material is an unusual form of iron oxide with the formula Fe₅O₆. The researchers produced it at a pressure of 15 gigapascals in a high-pressure laboratory...

Im Focus: From China to the South Pole: Joining forces to solve the neutrino mass puzzle

Study by Mainz physicists indicates that the next generation of neutrino experiments may well find the answer to one of the most pressing issues in neutrino physics

Among the most exciting challenges in modern physics is the identification of the neutrino mass ordering. Physicists from the Cluster of Excellence PRISMA+ at...

Im Focus: Therapies without drugs

Fraunhofer researchers are investigating the potential of microimplants to stimulate nerve cells and treat chronic conditions like asthma, diabetes, or Parkinson’s disease. Find out what makes this form of treatment so appealing and which challenges the researchers still have to master.

A study by the Robert Koch Institute has found that one in four women will suffer from weak bladders at some point in their lives. Treatments of this condition...

Im Focus: A step towards controlling spin-dependent petahertz electronics by material defects

The operational speed of semiconductors in various electronic and optoelectronic devices is limited to several gigahertz (a billion oscillations per second). This constrains the upper limit of the operational speed of computing. Now researchers from the Max Planck Institute for the Structure and Dynamics of Matter in Hamburg, Germany, and the Indian Institute of Technology in Bombay have explained how these processes can be sped up through the use of light waves and defected solid materials.

Light waves perform several hundred trillion oscillations per second. Hence, it is natural to envision employing light oscillations to drive the electronic...

Im Focus: Freiburg researcher investigate the origins of surface texture

Most natural and artificial surfaces are rough: metals and even glasses that appear smooth to the naked eye can look like jagged mountain ranges under the microscope. There is currently no uniform theory about the origin of this roughness despite it being observed on all scales, from the atomic to the tectonic. Scientists suspect that the rough surface is formed by irreversible plastic deformation that occurs in many processes of mechanical machining of components such as milling.

Prof. Dr. Lars Pastewka from the Simulation group at the Department of Microsystems Engineering at the University of Freiburg and his team have simulated such...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

70th Lindau Nobel Laureate Meeting: Around 70 Laureates set to meet with young scientists from approx. 100 countries

12.02.2020 | Event News

11th Advanced Battery Power Conference, March 24-25, 2020 in Münster/Germany

16.01.2020 | Event News

Laser Colloquium Hydrogen LKH2: fast and reliable fuel cell manufacturing

15.01.2020 | Event News

 
Latest News

Scientists 'film' a quantum measurement

26.02.2020 | Physics and Astronomy

Melting properties determine the biological functions of the cuticular hydrocarbon layer of ants

26.02.2020 | Interdisciplinary Research

Lights, camera, action... the super-fast world of droplet dynamics

26.02.2020 | Power and Electrical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>