“In vivo biosynthesis of N,N-dimethyltryptamine, 5-MeO-N,N-dimethyltryptamine, and bufotenine in E. coli”
Lucas M. Friedberg, Abhishek K. Sen, Quynh Nguyen, Gabriel P. Tonucci, Elle B. Hellwarth, William E. Gibbons, J. Andrew Jones
Metabolic Engineering May 23, 2023 DOI: 10.1016/j.ymben.2023.05.006 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Escherichia coli |
| Interventions | genetic optimization process optimization tryptophan supplementation |
| Topics | 5-MeO-DMT DMT |
| Keywords | Tryptamine Escherichia coli Fermentation Metabolic engineering Biochemistry In vivo Biosynthesis |
| Citations | 22 |
| Key findings | Biosynthetic production of DMT, 5-MeO-DMT, and bufotenine was achieved in Escherichia coli, with DMT titers reaching 74.7 ± 10.5 mg/L under fed-batch conditions. |
Abstract
N,N-dimethyltryptamine (DMT), 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and 5-hydroxy-N,N-dimethyltryptamine (bufotenine) are psychedelic tryptamines found naturally in both plants and animals and have shown clinical potential to help treat mental disorders, such as anxiety and depression. Advances in both metabolic and genetic engineering make it possible to engineer microbes as cell factories to produce DMT and its aforementioned derivatives to meet demand for ongoing clinical study. Here, we present the development of a biosynthetic production pathway for DMT, 5-MeO-DMT, and bufotenine in the model microbe Escherichia coli. Through the application of genetic optimization techniques and process optimization in benchtop fermenters, the in vivo production of DMT in E. coli was observed. DMT production with tryptophan supplementation reached maximum titers of 74.7 ± 10.5 mg/L under fed batch conditions in a 2-L bioreactor. Additionally, we show the first reported case of de novo production of DMT (from glucose) in E. coli at a maximum titer of 14.0 mg/L and report the first example of microbial 5-MeO-DMT and bufotenine production in vivo. This work provides a starting point for further genetic and fermentation optimization studies with the goal to increase methylated tryptamine production metrics to industrially competitive levels.
Comparable studies
Other experimental studies on 5-MeO-DMT, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Short term changes in the proteome of human cerebral organoids induced by 5-MeO-DMT. Human cerebral organoids | 2017 | Experimental study | |
| Bufo alvarius: a potent hallucinogen of animal origin. Bufo alvarius toad venom | 1994 | Experimental study | |
| Prospective examination of synthetic 5-methoxy-N,N-dimethyltryptamine inhalation: effects on salivary IL-6, cortisol levels, affect, and non-judgment Volunteers | 2019 | Within-subjects experimental study | n = 11 |
| Unmasking of a neonatal somatovesical reflex in adult cats by the serotonin autoreceptor agonist 5-methoxy-N,N-dimethyltryptamine. Adult cats | 1990 | Experimental study | n = 10 |
| Studies on the Mechanism of Action of Monoamine Oxidase: Metabolism of N,N-Dimethyltryptamine and N,N-Dimethyltryptamine-N-Oxide | 1962 | Experimental study |
Citations in the library
Cited by 16
- Exploring DMT: Endogenous role and therapeutic potential. Neuropharmacology May 1, 2025
- New frontiers in the biosynthesis of psychoactive specialized metabolites Current Opinion in Plant Biology September 16, 2024
- Exploring the biocatalysis of psilocybin and other tryptamines: Enzymatic pathways, synthetic strategies, and industrial implications Biotechnology Progress October 4, 2024
- Pathway engineering for the biosynthesis of psychedelics Current Opinion in Biotechnology May 15, 2025
- Evaluation of TrpM and PsiD substrate promiscuity reveals new biocatalytic capabilities Biotechnology Progress June 18, 2024
and 11 more in the library
Cites 13
- Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report Brazilian Journal of Psychiatry March 1, 2015
- Enzymatic Synthesis of Psilocybin Angewandte Chemie International Edition August 1, 2017
- Enzymatic Formation of Psychotomimetic Metabolites from Normally Occurring Compounds Science August 4, 1961
- Chemical evidence for the use of multiple psychotropic plants in a 1,000-year-old ritual bundle from South America. Proceedings of the National Academy of Sciences June 4, 2019
- Psychedelic 5-methoxy-N,N-dimethyltryptamine: metabolism, pharmacokinetics, drug interactions, and pharmacological actions. Current Drug Metabolism October 1, 2010
and 8 more in the library