Pathway engineering for the biosynthesis of psychedelics
Current Opinion in Biotechnology May 15, 2025 Zachary N Abrahms, Abhishek K. Sen, J. Andrew Jones 2 citations
Naturally occurring psychoactive compounds have been used for centuries in cultural and ethnomedical contexts, and many more have been chemically synthesized with varying potency, therapeutic, and hallucinogenic effects. Renewed interest from promising clinical data and a deeper understanding of cellular mechanisms has inspired synthetic biology efforts to create alternative production routes for psychedelic compounds. This review highlights recent biosynthetic achievements 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, and curates a list of biosynthetic enzymes with successful in vivo heterologous activity.