The fungivore-deterrence hypothesis, that psilocybin evolved as a chemical defence against arthropod fungivores via 5-HT receptor agonism, has become the working consensus in fungal chemical ecology, despite resting on a phylogenomic pattern of horizontal gene transfer among saprotrophs and remarkably little direct experimental evidence. Recent biochemistry ...
Stable, high-level biosynthesis of complex natural products requires precise control of heterologous pathway expression, yet transcriptional architectures optimized on plasmids often fail when transferred to the chromosome. Here, we present ePathIntegrate, a genome-centric pathway engineering strategy that leverages CRISPR-associated transposases (CASTs) to ...
Psilocybin, a tryptamine-derived alkaloid from Psilocybe mushrooms, has emerged as a high-value biopharmaceutical candidate due to its promising applications in mental health. While clinical studies highlight its rapid and sustained antidepressant effects, current challenges lie in achieving scalable, reproducible, and cost-effective production to meet growi...
ABSTRACT Psilocybin, an indole alkaloid of psychedelic mushrooms, has the potential to sustainably improve the treatment of several psychiatric diseases. So far, the psilocybin demand for clinical trials has been met by chemical synthesis. In this study, we pursued the biotechnological approach to develop a psilocybin production process utilizing an overprod...
Psilocybin, the psychoactive compound responsible for the hallucinogenic effects of “magic mushrooms,” is synthesized by a biosynthetic gene cluster (BGC) traditionally associated with Psilocybe species. However, psilocybin production has also been identified in multiple genera across the Strophariaceae, Hymenogastraceae, and Galeropsidaceae families. Here, ...
Psilocybin, a naturally occurring tryptamine alkaloid found in over 200 species of fungi, has emerged as a focal point in the modern revival of psychedelic science. Once relegated to the margins of psychopharmacology due to its association with counterculture and strict legal restrictions, psilocybin is now undergoing a scientific renaissance. This transform...
Research into psychedelic compounds is in resurgence due to the exciting potential for their use in the treatment of psychiatric and mental health disorders. Despite this revival, remarkably little is known about their evolution. One of the most intriguing psychedelic compounds is psilocybin, the compound found in ‘magic’ mushrooms and used in ritual ceremon...
Zusammenfassung Psilocybin (4-Phosphoryloxy- N, N -dimethyltryptamin, 1 ) ist der hauptsächliche Indolethylamin-Naturstoff der psychotropen sogenannten Zauberpilze. Die Mehrheit der 1 -produzierenden Arten gehört zu der namensgebenden Gattung Psilocybe, für die die biosynthetischen Ereignisse, ausgehend von l -Tryptophan ( 2 ), sowie die beteiligten Enzyme g...
Psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine, 1) is the main indolethyl-amine natural product of psychotropic (so-called "magic") mushrooms. The majority of 1-producing species belongs to the eponymous genus Psilocybe, for which the biosynthetic events, beginning from l-tryptophan (2), and the involved enzymes have thoroughly been characterized. Some I...
Naturally occurring psychoactive compounds have been used for cultural and ethnomedical purposes for centuries. Several more such molecules continue to be chemically synthesized, exhibiting a wide range of potency, therapeutic, and hallucinogenic effects. Promising clinical data and a renewed interest in understanding the cellular mechanisms of action have i...
Psilocybin, a tryptamine-derived alkaloid, has been granted Breakthrough Therapy designation by the U.S. FDA for treatment-resistant depression, underscoring its clinical importance. Therefore, sustainable and economic production is urgently needed. Manufacturing of psilocybin in Escherichia coli has drawn great attention. However, due to the low expression ...
Psilocybin shows significant therapeutic potential for psilocybin-assisted psychotherapy in addressing various psychiatric conditions. The biosynthetic approach promises rapid and efficient production of psilocybin. Understanding the enzymes that contribute to the biosynthesis of psilocybin can enhance its production process. In this study, we elucidate the ...
The growing body of evidence supporting the therapeutic efficacy of psychoactive substances, like psilocybin, has driven significant interest in recent decades due to their low toxicity and potential applications in treating various mental health disorders. However, producing pharmaceutical-grade psilocybin remains challenging, with three primary approaches:...
Psilocybe cubensis, a widely recognized psychoactive mushroom species, has played a significant role in both historical and modern therapeutic practices. This review explores the complex interplay between genetic diversity, strain variability and environmental factors that shape the biosynthesis of key psychoactive compounds, including psilocybin and psiloci...
IntroductionMushrooms, belonging to the phyla Ascomycota and Basidiomycota, comprise approximately 14,000 known species, among which a small fraction are toxic. While toxic mushrooms are primarily associated with adverse health effects, recent research highlights their potential as sources of bioactive compounds with promising therapeutic applications.Method...
Psilocybin, the natural hallucinogen from Psilocybe (magic) mushrooms, is a highly promising drug candidate for the treatment of depression and several other mental health conditions. Biosynthesis of psilocybin from the amino acid l-tryptophan involves four strictly sequential modifications. The third of these, ATP-dependent phosphorylation of the intermedia...
Abstract The Psilocybe cubensis SAM-dependent methyltransferase, PsiM, catalyzes the last step in the biosynthesis of psilocybin. Likely evolved from monomethylating RNA methyltransferases, PsiM acquired a key amino acid exchange in the secondary sphere of the active site, M247 N, which is responsible for its capacity to dimethylate. Two variants, PsiM N247M...
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...
