Tryptamines are neurotransmitters and psychoactive compounds found in many organisms. Psilocybin, a tryptamine, shows therapeutic potential for depression and anxiety, but current extraction methods are labor-intensive and costly. Biocatalysis—using enzymes—offers a sustainable alternative for synthesizing psilocybin and related tryptamines. Understanding psilocybin biosynthesis pathways can improve synthetic methods and industrial production. This review highlights biocatalysis's potential to advance tryptamine biosynthesis knowledge and enable high-purity production for therapy and research.
A two-step bacterial pathway converting L-tryptophan to the psychoactive alkaloid N,N-dimethyltryptamine (DMT) was reconstructed in Escherichia coli. The pathway combined a tryptophan decarboxylase from Ruminococcus gnavus and a methyltransferase from the cane toad Rhinella marina. Methionine supplementation increased DMT levels 2.8-fold, indicating that methylation capacity is a key constraint. In shake-flask cultures, a co-expression strain produced 103 mg/L DMT after 48 hours in complex medium. Using a tryptophan-enriched supernatant from Corynebacterium glutamicum enabled de novo DMT formation at 16 mg/L in defined medium. The findings identify methyltransferase capacity as a target for yield improvements.