Metabolic Engineering - The Consciousness Library

Genome-based optimization of psilocybin and N,N-dimethyltryptamine biosynthetic pathways in E. coli using CRISPR-associated transposases

Metabolic Engineering June 14, 2026 Zachary N. Abrahms, Mohammad Majdi, Siena M. Madsen et al.

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 integrate and rebalance multigene...

DOI: 10.1016/j.ymben.2026.102490 Psilocybin Transposase Escherichia coli Biosynthesis +4

Engineering artificial biosynthetic pathways for efficient microbial production of psilocybin and psilocin

Metabolic Engineering November 5, 2025 Cui Guo, Nguyen N T Luu, Maryem M Adwer et al. 5 citations

Psychedelic-assisted therapy is emerging as a highly promising approach for treating depression, with psilocybin, a psychoactive compound in magic mushrooms, gaining the most recognition for its efficacy in treating post-traumatic stress disorder and treatment-resistant depression. However, its low natural abundance makes extraction costly, necessitating alternative production methods. While...

DOI: 10.1016/j.ymben.2025.11.002 Psilocybin Metabolic engineering Escherichia coli Synthetic biology +11

Psilocybin biosynthesis enhancement through gene source optimization.

Metabolic Engineering April 16, 2025 Madeleine R Keller, Madeline G. Mckinney, Abhishek K. Sen et al. 8 citations

Psilocybin, the prodrug to the psychoactive compound in 'magic' mushrooms, is currently being studied in clinical trials as a treatment for severe mental health conditions, such as depression and anxiety. Previous reports of psilocybin biosynthesis as reconstituted in E. coli reported maximum titers of 1.16 g/L, exclusively using genes from the most common recreationally used mushroom,...

DOI: 10.1016/j.ymben.2025.04.003 Full text Gene source optimization Gymnopilus dilepis Norbaeocystin methyltransferase Promoter library +7

“In vivo biosynthesis of N,N-dimethyltryptamine, 5-MeO-N,N-dimethyltryptamine, and bufotenine in E. coli”

Metabolic Engineering May 23, 2023 Lucas M. Friedberg, Abhishek K. Sen, Quynh Nguyen et al. 22 citations

N,N-dimethyltryptamine (DMT), 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and 5-hydroxy-N,N-dimethyltryptamine (bufotenine) are psychedelic tryptamines found naturally in both plants and animals and have shown clinical potential to help treat mental disorders, such as anxiety and depression. Advances in both metabolic and genetic engineering make it possible to engineer microbes as cell...

DOI: 10.1016/j.ymben.2023.05.006 Tryptamine Escherichia coli Fermentation Metabolic engineering +3

Metabolic engineering of Saccharomyces cerevisiae for the de novo production of psilocybin and related tryptamine derivatives

Metabolic Engineering March 26, 2020 N. Milne, Philip Tinggaard Thomsen, Niels Aage Tvis Knudsen et al. 126 citations

Psilocybin is a tryptamine-derived psychoactive alkaloid found mainly in the fungal genus Psilocybe, among others, and is the active ingredient in so-called "magic mushrooms". Although its notoriety originates from its psychotropic properties and popular use as a recreational drug, clinical trials have recently recognized psilocybin as a promising candidate for the treatment of various...

DOI: 10.1016/j.ymben.2019.12.007 Psilocybin Tryptamine Saccharomyces cerevisiae Metabolic engineering +1

In vivo production of psilocybin in E. coli

Metabolic Engineering September 21, 2019 Alexandra M. Adams, Nicholas A. Kaplan, Zhangyue Wei et al. 83 citations

Psilocybin, the prodrug of the psychoactive molecule psilocin, has demonstrated promising results in clinical trials for the treatment of addiction, depression, and post-traumatic stress disorder. The development of a psilocybin production platform in a highly engineerable microbe could lead to rapid advances towards the bioproduction of psilocybin for use in ongoing clinical trials. Here, we...

DOI: 10.1016/j.ymben.2019.09.009 Psilocybin Bioproduction Recombinant dna Escherichia coli +2

Facile assembly and fluorescence-based screening method for heterologous expression of biosynthetic pathways in fungi

Metabolic Engineering May 26, 2018 Sandra Hoefgen, Jun Lin, Janis Fricke et al. 113 citations

Heterologous expression of multi-gene biosynthetic pathways in eukaryotic hosts is limited by highly regulated individual monocistrons. Dissimilar to prokaryotes, each eukaryotic gene is strictly controlled by its own regulatory elements, such as promoter and terminator. Consequently, parallel transcription can occur only when a group of genes is synchronously activated. A strategy to...

DOI: 10.1016/j.ymben.2018.05.014 Aspergillus nidulans Heterologous expression Terminator solar Promoter +6

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