“Biosynthesis of psilocybin and its nonnatural derivatives by a promiscuous psilocybin synthesis pathway in Escherichia coli”
Biotechnology and Bioengineering – June 20, 2023
Source: OpenAlex
Summary
A significant advance in biochemistry enables the biosynthesis of psilocybin, a potent hallucinogen, and 13 new derivatives using bacteria. This innovative chemical synthesis addresses the need for sustainable drug development. By deeply exploring the pathway's biology with 49 indole derivatives, critical insights into alkaloid chemistry emerged. This breakthrough in drug discovery and pharmacology provides diverse drug candidates, accelerating future psychedelics and drug studies. This method promises a consistent supply for vital research.
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.