British Journal of Pharmacology
June 2, 2024
Oscar Sandoval, Quynh Nguyen, Ryan J. Rakoczy et al.
23 citations
Several tryptamines found in psilocybin-containing mushrooms—baeocystin, norbaeocystin, and aeruginascin—were compared with psilocybin to assess their pharmacological and behavioral effects. All compounds showed nearly identical rates of dephosphorylation and metabolism by monoamine oxidase. Only dephosphorylated baeocystin and norbaeocystin crossed a blood–brain barrier mimetic as effectively as psilocin. Norbaeocystin's dephosphorylated form activated the 5-HT2A receptor with similar efficacy to psilocin and norpsilocin. While only psilocybin induced head twitch responses in rats (a marker of hallucinogenic potential), norbaeocystin, like psilocybin, improved outcomes in the forced swim test. All compounds showed minimal changes to renal and hepatic health markers, suggesting safe profiles. Norbaeocystin may share therapeutic potential with psilocybin without causing hallucinations.
Metabolic Engineering
May 23, 2023
Lucas M. Friedberg, Abhishek K. Sen, Quynh Nguyen et al.
22 citations
Psychedelic tryptamines such as DMT, 5-MeO-DMT, and bufotenine, found naturally in plants and animals, show clinical promise for treating anxiety and depression. Using genetic and metabolic engineering, researchers developed a biosynthetic pathway in Escherichia coli to produce these compounds. With tryptophan supplementation, DMT reached maximum titers of 74.7 ± 10.5 mg/L in fed-batch 2-L bioreactors. De novo DMT production from glucose achieved 14.0 mg/L, and the study reports the first microbial production of 5-MeO-DMT and bufotenine in vivo. This work establishes a foundation for further optimization toward industrial-scale production.
Bioengineered
January 1, 2021
William E. Gibbons, Madeline G. Mckinney, Philip J. O’dell et al.
8 citations
Psilocybin, a recreational psychedelic, is being studied as a therapy for depression, anxiety, and addiction. Recent advances include biosynthesis using microorganisms. This work demonstrates production of approximately 300 mg/L of psilocybin in less than 2 days using a recombinant E. coli strain in a simple, homebrew-style setup with easily sourced equipment. The finding raises regulatory questions about preventing clandestine synthesis while allowing pharmaceutical development. The authors present their results and suggestions for addressing these regulatory concerns.
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.
bioRxiv (Cold Spring Harbor Laboratory)
October 23, 2023
Ryan J. Rakoczy, Grace N. Runge, Abhishek K. Sen et al.
preprint
Naturally occurring tryptamines in psilocybin-containing mushrooms—baeocystin, norbaeocystin, and aeruginascin—were compared with psilocybin for pharmacological and behavioral effects. All compounds showed nearly identical rates of dephosphorylation and metabolism. Only dephosphorylated forms of baeocystin and norbaeocystin crossed a blood-brain barrier model similarly to psilocin (psilocybin's active form). In rats, only psilocybin triggered head twitch responses (a marker of hallucinogenic potential), but norbaeocystin, like psilocybin, improved outcomes in the forced swim test. All compounds showed minimal effects on renal and hepatic health markers. The findings suggest norbaeocystin may share psilocybin's therapeutic potential without causing hallucinations.