Optimized psilocybin production in tryptophan catabolism‐repressed fungi

Nov 2, 2024Microbial biotechnology

Increased psilocybin production in fungi with reduced tryptophan breakdown

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Abstract

A final titre of 267 mg/L was achieved in optimized batch cultures.

  • Psilocybin is a prodrug of psilocin with potential to treat mental disorders such as depression and alcohol use disorder.
  • In Saccharomyces cerevisiae, deleting specific genes increased psilocybin production by fivefold.
  • Functional orthologs of key genes were identified in Aspergillus nidulans, which also showed a tenfold increase in psilocybin production upon gene deletion.
  • Process optimization through respiratory activity measurements improved the yield of psilocybin in batch cultures.
  • The engineered A. nidulans strain may be suitable for large-scale production of psilocybin and other related pharmaceuticals.

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Key numbers

10×
Increase in Production
Production in A. nidulans double deletion mutant vs. wild-type strains
267 mg/L
Final Titre
Achieved in batch cultures of the engineered A. nidulans strain
3.7 mg/L/h
Space-Time Yield
Calculated from the maximum production over cultivation time

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