In vivo production of psilocybin in E. coli

Introduction

Adams and colleagues situate their work against renewed clinical interest in psilocybin, a prodrug of psilocin that has shown therapeutic promise in trials for conditions such as depression, anxiety in terminal cancer and post‑traumatic stress disorder. Chemical synthesis of psilocybin is possible but remains multi‑step and costly; recent work by other groups identified the fungal biosynthetic genes and demonstrated in vitro and eukaryotic in vivo production, but reported titres from recombinant fungal hosts remained modest. The authors frame a gap around the need for a more easily engineered, cost‑effective microbial production platform that could support larger scale and potentially industrial manufacture for clinical use. This study aimed to heterologously express the key psilocybin biosynthetic genes from Psilocybe cubensis in the prokaryotic host Escherichia coli and to optimise production through parallel genetic library strategies and fermentation parameter tuning. The objective was to demonstrate proof‑of‑principle in E. coli, identify a genetically superior strain, and scale production in a fed‑batch bioreactor to assess whether a bacterial host could reach competitive titres compared with previously reported fungal systems.