A cane toad (Rhinella marina) N-methyltransferase converts primary indolethylamines to tertiary psychedelic amines

Chen, Xue; Li, Jing; Yu, Lisa; Maule, Francesca; Chang, Limei; Gallant, Jonathan A.; Press, David J.; Raithatha, Sheetal A.; Hagel, Jillian M.; Facchini, Peter J.

doi:10.1016/j.jbc.2023.105231

Cited by 5 publications

(4 citation statements)

References 64 publications

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“…Recently, a novel indolethylamine-N-methyltransferase in the skin and parotid glands of some toad species has been cloned (Chen et al, 2023). This enzyme probably underlies the production of bufotenin in the skin of particular toad species (e.g., Bufo marinus, Bufo Bufo) that are known to be used as sources of bufotenin (Chen et al, 2023). This novel enzyme is absent in common frogs (Chen et al, 2023).…”

Section: Bufoteninmentioning

confidence: 99%

“…This enzyme probably underlies the production of bufotenin in the skin of particular toad species (e.g., Bufo marinus, Bufo Bufo) that are known to be used as sources of bufotenin (Chen et al, 2023). This novel enzyme is absent in common frogs (Chen et al, 2023). In toads, biosynthesis starts with tryptophan, which is hydroxylated to 5-hydroxytryptophan and then decarboxylated, leading to serotonin.…”

Section: Bufoteninmentioning

confidence: 99%

“…The primary amine in serotonin is first methylated to monomethylserotonin. This secondary amine is then methylated again to the tertiary amine N,Ndimethylserotonin (bufotenin, Chen et al, 2023).…”

Section: Bufoteninmentioning

confidence: 99%

“…The decisive next step is catalysed by the high turnover rates of a particular enzyme in some species of toads (as mentioned above for bufotenin). Tryptamine is then sequentially methylated via monomethyltryptamine to DMT via a newly cloned indolethylamine methylase found, especially in Bufo marinus (Chen et al, 2023).…”

Section: Nn-dimethyltryptamine (Dmt)mentioning

confidence: 99%

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Effects of hallucinogenic drugs on the human heart

Neumann,

Dhein,

Kirchhefer

et al. 2024

Front. Pharmacol.

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Hallucinogenic drugs are used because they have effects on the central nervous system. Their hallucinogenic effects probably occur via stimulation of serotonin receptors, namely, 5-HT2A-serotonin receptors in the brain. However, a close study reveals that they also act on the heart, possibly increasing the force of contraction and beating rate and may lead to arrhythmias. Here, we will review the inotropic and chronotropic actions of bufotenin, psilocin, psilocybin, lysergic acid diethylamide (LSD), ergotamine, ergometrine, N,N-dimethyltryptamine, and 5-methoxy-N,N-dimethyltryptamine in the human heart.

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Section: Bufoteninmentioning

confidence: 99%

Section: Bufoteninmentioning

confidence: 99%

Section: Bufoteninmentioning

confidence: 99%

Section: Nn-dimethyltryptamine (Dmt)mentioning

confidence: 99%

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Effects of hallucinogenic drugs on the human heart

Neumann,

Dhein,

Kirchhefer

et al. 2024

Front. Pharmacol.

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Evaluation of TrpM and PsiD substrate promiscuity reveals new biocatalytic capabilities

Kanis,

Broude,

Hellwarth

et al. 2024

Biotechnology Progress

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N‐methylated tryptamines, such as the hallucinogenic natural products, psilocybin and N,N‐dimethyltryptamine (DMT), are gaining interest from the medical community due to their potential as next generation treatments for mental health disorders. The clinical relevance of these compounds has driven scientists to develop biosynthetic production routes to a number of tryptamine drug candidates, and efforts are ongoing to expand and further develop these biosynthetic capabilities. To that end, we have further characterized the substrate preferences of two enzymes involved in tryptamine biosynthesis: TrpM, a tryptophan N‐methyltransferase from Psilocybe serbica, and PsiD, the gateway decarboxylase of the psilocybin biosynthesis pathway. Here, we show that TrpM can N‐methylate the non‐native amino acid substrate, 4‐hydroxytryptophan, a key intermediate in the Escherichia coli‐based recombinant psilocybin biosynthesis pathway. However, the ability to incorporate TrpM into a functional psilocybin biosynthesis pathway was thwarted by PsiD's inability to use N,N‐dimethyl‐4‐hydroxytryptophan as substrate, under the culturing conditions tested, despite demonstrating activity on N‐methylated and 4‐hydroxylated tryptophan derivatives individually. Taken together, this work expands upon the known substrates for TrpM and PsiD, further increasing the diversity of tryptamine biosynthetic products.

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Exploring the biocatalysis of psilocybin and other tryptamines: Enzymatic pathways, synthetic strategies, and industrial implications

Junges,

Müller‐Santos

2024

Biotechnology Progress

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Tryptamines play diverse roles as neurotransmitters and psychoactive compounds found in various organisms. Psilocybin, a notable tryptamine, has garnered attention for its therapeutic potential in treating mental health disorders like depression and anxiety. Despite its promising applications, current extraction methods for psilocybin are labor‐intensive and economically limiting. We suggest biocatalysis as a sustainable alternative, leveraging enzymes to synthesize psilocybin and other tryptamines efficiently. By elucidating psilocybin biosynthesis pathways, researchers aim to advance synthetic methodologies and industrial applications. This review underscores the transformative potential of biocatalysis in enhancing our understanding of tryptamine biosynthesis and facilitating the production of high‐purity psilocybin and other tryptamines for therapeutic and research use.

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A cane toad (Rhinella marina) N-methyltransferase converts primary indolethylamines to tertiary psychedelic amines

Cited by 5 publications

References 64 publications

Effects of hallucinogenic drugs on the human heart

Effects of hallucinogenic drugs on the human heart

Evaluation of TrpM and PsiD substrate promiscuity reveals new biocatalytic capabilities

Exploring the biocatalysis of psilocybin and other tryptamines: Enzymatic pathways, synthetic strategies, and industrial implications

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