In vivo production of psilocybin in E. coli
Alexandra M. Adams, Nicholas A. Kaplan, Zhangyue Wei, John D. Brinton, Chantal Monnier, Alexis L. Enacopol, Theresa A. Ramelot, J. Andrew Jones
Metabolic Engineering September 21, 2019 DOI: 10.1016/j.ymben.2019.09.009 via OpenAlex
Summary
AI-generated from the abstractA modular biosynthetic production platform for psilocybin was developed in the model microbe Escherichia coli. Multiple genetic optimization techniques improved psilocybin titer by 32-fold. Further fermentation optimization in a fed-batch study achieved a production titer of 1.16 g/L of psilocybin, the highest titer reported from a recombinant organism to date. This work demonstrates progress toward the industrial bioproduction of psilocybin for clinical use.
Study at a glance
| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Escherichia coli |
| Topics | Psilocybin |
| Keywords | Bioproduction Recombinant dna Escherichia coli Biology |
| Citations | 83 |
| Key finding | A fed-batch fermentation study achieved a psilocybin titer of 1.16 g/L, the highest from a recombinant organism. |
Abstract
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 present the development of a modular biosynthetic production platform in the model microbe, Escherichia coli. Efforts to optimize and improve pathway performance using multiple genetic optimization techniques were evaluated, resulting in a 32-fold improvement in psilocybin titer. Further enhancements to this genetically superior strain were achieved through fermentation optimization, ultimately resulting in a fed-batch fermentation study, with a production titer of 1.16 g/L of psilocybin. This is the highest psilocybin titer achieved to date from a recombinant organism and a significant step towards demonstrating the feasibility of industrial production of biologically-derived psilocybin.