ArticleMetabolic engineering2020
Metabolic engineering of Saccharomyces cerevisiae for the de novo production of psilocybin and related tryptamine derivatives.
Article in Metabolic engineering, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 119 citations in OpenAlex.
- Synthesis of Amines for Active Pharmaceutical Ingredients Using the Whole-Cell Factory Saccharomyces Cerevisae.Chembiochem : a European journal of chemical biology · 2026Review
- Complete biosynthesis of psychedelic tryptamines from three kingdoms in plants.Science advances · 2026Article
- Psilocybin Production With Genetically Modified Aspergillus nidulans Under Pressurized Conditions.Biotechnology and bioengineering · 2026Article
- Simplifying multiplex genome engineering in Saccharomyces cerevisiae with intron-mediated Random Assembly and INtegration (RAIN).FEMS yeast research · 2026Article
- Engineering yeast for sustainable bioproduction of tryptophan-derived aromatic compounds.FEMS yeast research · 2026Review
- Psilocybin: clinical potential, mechanistic insights, and biotechnological advances for scalable production.World journal of microbiology & biotechnology · 2025Review
- Dissimilar Reactions and Enzymes for Psilocybin Biosynthesis in Inocybe and Psilocybe Mushrooms.Angewandte Chemie (International ed. in English) · 2025Article
- Advances in integrating microbial metabolism with catalytic systems.Nature chemical biology · 2025Review
- Reconstitution of Human Cytochrome P450 Activity using aACS synthetic biology · 2025Article
- Combinatorial engineering pinpoints shikimate pathway bottlenecks in para-aminobenzoic acid production in Pseudomonas putida.Journal of biological engineering · 2025Article
- Biochemical Insights into Diverse Psilocybe Mushrooms and Their Metabolites as Sources of Neuroactive Agents: A Review.Current microbiology · 2025Review
- Bioproduction of 3,4-methylenedioxymethamphetamine and derivatives.Biodesign research · 2025Article
- In Vitro Psilocybin Synthesis by Co-Immobilized Enzymes.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
- Synthetic Biology in Natural Product Biosynthesis.Chemical reviews · 2025Review
- The Emergence of Psilocybin in Psychiatry and Neuroscience.Pharmaceuticals (Basel, Switzerland) · 2025Review
- De Novo Biosynthesis of Antidepressant Psilocybin in Escherichia coli.Microbial biotechnology · 2025Article
- Metabolic Engineering of a Serotonin Overproducing Saccharomyces cerevisiae Strain.Microbial biotechnology · 2025Article
- Structural basis for psilocybin biosynthesis.Nature communications · 2025Article
- Substrate recognition by the 4-hydroxytryptamine kinase PsiK in psilocybin biosynthesis.FEBS letters · 2025Article
- Adaptive laboratory evolution of Saccharomyces cerevisiae CEN.PK 113-7D to enhance ethanol tolerance.FEMS yeast research · 2025Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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 psychological and neurological afflictions. In this work, we demonstrate the de novo biosynthetic production of psilocybin and related tryptamine derivatives in Saccharomyces cerevisiae by expression of a heterologous biosynthesis pathway sourced from Psilocybe cubensis. Additionally, we achieve improved product titers by supplementing the pathway with a novel cytochrome P450 reductase from P. cubensis. Further rational engineering resulted in a final production strain producing 627 ± 140 mg/L of psilocybin and 580 ± 276 mg/L of the dephosphorylated degradation product psilocin in triplicate controlled fed-batch fermentations in minimal synthetic media. Pathway intermediates baeocystin, nor norbaeocystin as well the dephosphorylated baeocystin degradation product norpsilocin were also detected in strains engineered for psilocybin production. We also demonstrate the biosynthetic production of natural tryptamine derivative aeruginascin as well as the production of a new-to-nature tryptamine derivative N-acetyl-4-hydroxytryptamine. These results lay the foundation for the biotechnological production of psilocybin in a controlled environment for pharmaceutical applications, and provide a starting point for the biosynthetic production of other tryptamine derivatives of therapeutic relevance.
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