“Biosynthesis of psilocybin and its nonnatural derivatives by a promiscuous psilocybin synthesis pathway in Escherichia coli”
Jessica E. Flower, William J Gibbons, Alexandra M. Adams, Xin Wang, Caroline N. Broude, J Andrew Jones
Biotechnology and Bioengineering June 20, 2023 DOI: 10.1002/bit.28480 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Topics | Psilocybin |
| Keywords | Co-cultures Enzyme promiscuity Tryptamine Tryptophan synthase Biosynthesis Psychedelic compounds Metabolic engineering Enzyme engineering Pharmaceutical production |
| Citations | 26 |
| Key findings | Incorporating PsiH into the bacterial psilocybin pathway enables de novo production of psilocybin and 13 derivatives, and the pathway's substrate promiscuity allows biosynthesis of a library of previously unstudied drug candidates. |
Abstract
Abstract Traditional psychedelics are undergoing a transformation from recreational drugs, to promising pharmaceutical drug candidates with the potential to provide an alternative treatment option for individuals struggling with mental illness. Sustainable and economic production methods are thus needed to facilitate enhanced study of these drug candidates to support future clinical efforts. Here, we expand upon current bacterial psilocybin biosynthesis by incorporating the cytochrome P450 monooxygenase, PsiH, to enable the de novo production of psilocybin as well as the biosynthesis of 13 psilocybin derivatives. The substrate promiscuity of the psilocybin biosynthesis pathway was comprehensively probed by using a library of 49 single‐substituted indole derivatives, providing biophysical insights to this understudied metabolic pathway and opening the door to the in vivo biological synthesis of a library of previously unstudied pharmaceutical drug candidates.