Pathway engineering for the biosynthesis of psychedelics
Zachary N. Abrahms, Abhishek K. Sen, J. Andrew Jones
Current Opinion in Biotechnology May 15, 2025 DOI: 10.1016/j.copbio.2025.103314 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | LSD Mescaline Psilocybin Serotonin |
| Keywords | Hallucinogen Drug discovery Pharmacology Biochemistry |
| Citations | 2 |
| Key findings | Recent biosynthetic advances have enabled production of indolamines, ergolines, and phenethylamines in both eukaryotic and prokaryotic hosts, with a curated list of enzymes showing successful in vivo heterologous activity. |
Abstract
Naturally occurring psychoactive compounds have been used for cultural and ethnomedical purposes for centuries. Several more such molecules continue to be chemically synthesized, exhibiting a wide range of potency, therapeutic, and hallucinogenic effects. Promising clinical data and a renewed interest in understanding the cellular mechanisms of action have inspired synthetic biology efforts to develop alternative production routes for psychedelic compounds. Here, we highlight the latest biosynthetic accomplishments for indolamines (psilocybin, N,N-dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine, and bufotenine), ergolines (lysergic acid), and phenethylamines (mescaline) in both eukaryotic and prokaryotic production hosts. We further curate a list of relevant biosynthetic enzymes that have reports of successful in vivo heterologous activity.