Complete biosynthesis of psychedelic tryptamines from three kingdoms in plants

Area of Science:

• * Biochemistry and metabolic engineering of natural products.
• * Exploration of plant-based pharmaceutical production.

Background:

• * Psychedelic indolethylamines, such as N,N-dimethyltryptamine (DMT), psilocin, and psilocybin, possess therapeutic potential.
• * These compounds are naturally found in plants, fungi, and animals, with traditional uses in shamanic rituals.

Purpose of the Study:

• * To elucidate and reconstruct the complete biosynthetic pathway of DMT in hallucinogenic plants.
• * To engineer a versatile plant-based platform for the production and diversification of multiple psychoactive indolethylamines.

Main Methods:

• * Reconstruction of five natural psychedelic biosynthetic pathways (psilocin, psilocybin, DMT, bufotenin, 5-methoxy-DMT) in a single plant assay.
• * Engineering of novel halogenated analogs of these psychedelics.
• * Application of metabolic engineering and rational protein design for enhanced in planta production.

Main Results:

• * Successful reconstruction of multiple indolethylamine biosynthetic pathways within a plant system.
• * Demonstrated efficient in planta production of key psychedelic components through enzyme engineering.
• * Engineered novel halogenated analogs with potential therapeutic applications.

Conclusions:

• * Established a versatile platform for the concurrent biosynthesis and diversification of psychoactive indolethylamines in plants.
• * This work paves the way for sustainable and scalable plant-based production of these compounds for therapeutic use.