Weizmann Institute researchers have deciphered the DMT production pathway in plants and integrated genes from plants, fungi, and animals into a model plant. The system may be used in the future for controlled production of compounds for research and drug development – but is not intended for direct consumption
The researchers produced the model plant Nicotiana benthamiana, a relative of tobacco, the DMT found in certain plants; the Psilocybin וPsilocin, known from mushrooms; and bufotenine and 5-MeO-DMT, found, among other things, in the secretions of the Sonoran desert toad. This does not mean that the plant itself is intended for medical use or consumption: at this stage it is an experimental system for producing chemicals and examining their production pathways.
From the same building block – to different paths
The five compounds belong to a similar chemical family and are built from a common starting material: tryptophan, an amino acid used by living organisms to produce a variety of molecules. In the human body, tryptophan is also used as a raw material to create serotonin, a neurotransmitter involved in, among other things, regulating mood. The structural similarity between the compounds allowed researchers to combine enzymes from different biological sources in one plant and recreate pathways that evolved separately in nature.
The first step was to complete the picture of the DMT production pathway in plants. The general pathway was known, but the precise identity of some of the genes and enzymes that carry out its steps was unclear. The researchers examined plants that naturally produce DMT, identified candidate genes, and transferred them to the model plant. Within a few days, measurable amounts of the substance were found in its tissues.
The pathways for the production of the other four compounds were then also reconstructed in the plant. One of the challenges was the production of 5-MeO-DMT, which was initially obtained in small quantities. Analysis of the enzyme's structure showed that one of the intermediate molecules did not fit well into its active site. Changing a single amino acid in the protein improved its fit and increased the yield of the substance by 40 times. Dr. Shirley Paula Berman, who led the work, concluded: “We changed one amino acid in the protein sequence, and we got a 40-fold increase.”
When production routes compete with each other
When the researchers combined all the pathways in the plant, they were able to identify all five compounds simultaneously. However, a limitation also became apparent: the different pathways competed for the same raw materials. The competition created a bottleneck and reduced the output of some molecules. Solving the problem will require adjusting enzyme levels, increasing the supply of starting materials, or separating different stages within the plant cells.
The researchers also expanded the system beyond naturally occurring substances. By combining bacterial enzymes, they created derivatives in which chlorine or bromine atoms were added to the molecules. Such modifications may alter the stability, receptor affinity, and duration of activity of the compounds, making them of interest to the field of drug discovery. However, initial laboratory activity does not prove that the molecules are effective or safe for human treatment; this will require preclinical studies and well-designed clinical trials.
An alternative to extraction from nature
Establishing controlled production systems also has an environmental aspect. The supply of some materials for research currently relies on growing or collecting plants and fungi and sometimes animals. The researchers note that collecting from natural sources may raise problems of habitat damage, overexploitation and animal welfare. Rapidly growing laboratory plants may provide a more uniform alternative, where the quality and composition of the material is easy to control.
The broader significance of the research is not limited to psychedelic compounds. It demonstrates how biochemical pathways that evolved on distant branches of the tree of life can be connected in a single plant, enzymes can be improved through protein engineering, and new molecules can be produced. In the future, model plants To serve not only as a source of natural materials, but also as platforms for the development and production of new drug candidates.
The study was conducted under the leadership of Dr. Shirley Paula Berman and Prof. Assaf Aharoni, with the participation of researchers from Prof. Sarel Fleischman's laboratory at the Weizmann Institute, the Volcanic Institute, and the Technion.
Questions and Answers:
Have researchers created a new strain of commercial tobacco? No. They used theNicotiana benthamiana, a popular model plant in biological research, for the transient expression of genes and examination of metabolic pathways.
What is the main innovation? Deciphering the complete DMT production pathway in plants and integrating pathways originating from three natural kingdoms within a single plant system.
Are the compounds created already drugs? No. These are research materials and potential candidates for development. Extensive testing of efficacy, dosage, toxicity, and safety is required.
Why produce the materials in plants? Plants can grow rapidly, perform complex chemical reactions, and provide a scalable and controllable production system, reducing reliance on collection from natural sources.
Amp: Yes
For the original publication: Opening the original publication
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4 תגובות
How come they haven't found a cure that can eliminate or shrink a cancerous tumor? All these years
Can you please put together a plant for me that consists of marijuana, tobacco, gat, and red bemba?
The plant is called in Latin Achoshermotico stellus.
Serotonin is involved in brain activity in general. It has not been proven to be involved in mood regulation. This is a superstition of bad academics. In fact, a study came out a few years ago that closed this corner. It is worth updating and being accurate accordingly.