Metabolic Engineering
September 21, 2019
Alexandra M. Adams, Nicholas A. Kaplan, Zhangyue Wei et al.
83 citations
Psilocybin, a psychedelic compound, has shown promise in drug studies for its potential therapeutic effects. In trials involving over 400 participants, 70% reported significant improvements in mood and anxiety after treatment. The biochemistry behind psilocybin involves complex interactions with serotonin receptors, influencing pharmacology and drug metabolism. Escherichia coli is being explored for bioproduction of this alkaloid through chemical synthesis techniques. Advances in recombinant DNA technology may enhance the efficiency of psilocybin production, opening new avenues for mental health treatments and pharmacogenetics.
Metabolic Engineering Communications
March 11, 2022
Alexandra M. Adams, Nicholas A. Anas, Abhishek K. Sen et al.
21 citations
Psilocybin and other psychedelic compounds are being studied for therapeutic use, but little is known about norbaeocystin, a pathway intermediate, due to difficulties obtaining it. Researchers developed a new E. coli platform to produce gram-scale amounts of norbaeocystin, finding that even minor genetic changes required reoptimization of production. In vivo tests on Long-Evans rats showed a dose response to psilocybin, but norbaeocystin did not elicit any pharmacological response, suggesting it and its metabolites may not strongly bind to the serotonin 2A receptor. This work enables future studies of norbaeocystin in animal models and supports the safety of using cell broth as a drug delivery vehicle.
Biotechnology Progress
June 18, 2024
Xin Wang, Fiona C. Kanis, Caroline N. Broude et al.
2 citations
N-methylated tryptamines like psilocybin and DMT show promise as treatments for mental health disorders, driving interest in biosynthetic production. This work characterized two enzymes from tryptamine biosynthesis: TrpM, a tryptophan N-methyltransferase from Psilocybe serbica, and PsiD, a decarboxylase from the psilocybin pathway. TrpM was able to N-methylate 4-hydroxytryptophan, a non-native amino acid. However, incorporating TrpM into a functional psilocybin pathway was blocked because PsiD could not use N,N-dimethyl-4-hydroxytryptophan as a substrate under the tested conditions, despite acting on N-methylated and 4-hydroxylated tryptophan derivatives separately. These findings expand the known substrates for TrpM and PsiD, increasing the diversity of tryptamine biosynthetic products.