Scientists at the Weizmann Institute of Science have engineered Nicotiana benthamiana, a fast-growing relative of tobacco, to produce five different psychedelic compounds.Â
The achievement, detailed in a study published in Science Advances, brings together biosynthetic pathways that nature distributes across three different kingdoms of life.
The five compounds (DMT, psilocybin, psilocin, bufotenin, and 5-MeO-DMT) are typically sourced from an Amazonian shrub, mushrooms, and the defensive skin glands of a desert toad. Extracting even one of these molecules from its natural source is a slow process. Producing all five in a single, easily cultivated plant had not been achieved before.
A Shared Chemical Ancestor
Despite coming from such different sources, all five of these molecules share a common origin: tryptophan, an amino acid found in every living thing. In humans, tryptophan is the building block for serotonin, which helps explain why these psychedelics interact with serotonin receptors in the brain. This shared chemistry gave the Weizmann team, led by Dr. Paula Berman and Prof. Asaph Aharoni, a logical starting point for their experiments.
The team began by focusing on DMT to address a previously unresolved question. Researchers knew the general biochemical pathway plants use to synthesize DMT, but they had not yet identified all the genes and enzymes responsible for each step. “At the heart of the study was the challenge of making DMT,” Aharoni says.
To identify the necessary genes, the team analyzed genetic material from the Amazonian chacruna shrub and an Australian acacia species. Introducing these genes into Nicotiana benthamiana allowed the plant to produce DMT within days.
Fixing a Bottleneck With One Amino Acid
The researchers applied the same gene transfer approach to the other four psychedelics, but the engineered plants initially produced only trace amounts of 5-MeO-DMT. Protein-design specialists Prof. Sarel Fleishman and Dr. Olga Khersonsky determined that the limitation was due to a poor molecular fit in one enzyme’s active site. Replacing a single amino acid resolved the issue.
“We mutated one amino acid in the sequence and got a 40-fold increase in the production of 5-MeO-DMT,” Berman says.
One Organism, Three Kingdoms
Once all five biosynthetic pathways were functioning separately, the researchers combined them within a single plant. The result was a tobacco relative capable of producing DMT from plants, psilocin and psilocybin from fungi, and bufotenin and 5-MeO-DMT from toads, all at the same time. “In effect, we created a kind of biological ‘cocktail’ — not by mixing substances externally, but by combining the underlying pathways inside one organism,” Aharoni says.
Combining all five pathways reduced the yield of each compound, as they competed for the same pool of tryptophan. The researchers also introduced bacterial enzymes to attach chlorine and bromine atoms to the psychedelic molecules, creating modified psychedelic molecules that do not naturally occur in the engineered plant. Some similar modified molecules have shown antidepressant-like effects in previous studies.
Why the Compounds Exist in the First Place
The bottleneck also highlighted a broader research question about the natural role of these compounds. These molecules likely function as defenses or as tools for interacting with microbes and insects in the organisms that produce them, rather than evolving to affect human consciousness.
“If we can move these pathways into a model plant that grows quickly and is easy to manipulate, we can start asking what these compounds actually do for the plant,” Berman explains.
A Sustainable Supply Line
There is a clear practical benefit to this approach. Plants used for ayahuasca are increasingly threatened by habitat loss and rising demand, and the Sonoran Desert toad is declining due to overcollection and habitat destruction. A fast-growing laboratory plant capable of producing these compounds within a week provides an alternative that does not rely on harvesting wild species.
The Weizmann researchers are now working on a plant that can produce the complete ayahuasca mixture, which includes both DMT and the compound required for it to be active when taken orally. They are also exploring whether these psychedelics could be produced in edible plants capable of delivering carefully regulated doses.
Whether this platform becomes a practical manufacturing system will depend on overcoming the metabolic bottleneck that currently limits production when multiple pathways operate simultaneously.
Austin Burgess is a writer and researcher with a background in sales, marketing, and data analytics. He holds an MBA, a Bachelor of Science in Business Administration, and a data analytics certification. His work focuses on breaking scientific developments, with an emphasis on emerging biology, cognitive neuroscience, and archaeological discoveries.