A cane toad (Rhinella marina) N-methyltransferase converts primary indolethylamines to tertiary psychedelic amines.
The Journal of biological chemistry October 1, 2023 Xue Chen, Jing Li, Lisa Yu et al. 13 citations
A novel indolethylamine N-methyltransferase (RmNMT) from the cane toad (Rhinella marina) was identified and characterized. This enzyme catalyzes the biosynthesis of psychedelic alkaloids such as DMT, 5-methoxy-DMT, and bufotenin, which accumulate in toad skin and parotid glands and have been used ceremonially by Mesoamerican peoples. RmNMT is an effective catalyst not subject to product inhibition and exhibits substrate promiscuity, enabling production of various substituted indolethylamines for purification, pharmacological screening, and metabolic stability assays. Binding evaluations at serotonin receptors showed that primary amines have enhanced affinity at the 5-HT1A receptor compared with tertiary amines. Except for 6-substituted derivatives, N,N-dimethylation protected against catabolism by liver microsomes.