Reconstituting a two-step pathway for N,N-dimethyltryptamine (DMT) biosynthesis in bacteria
Metabolic Engineering Communications July 1, 2026 Lucas Henrique Junges, Flávia Lada Degaut Pontes, Francisco J. Teles Mota et al.
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.