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"Biosynthesis of psilocybin and its nonnatural derivatives by a promiscuous psilocybin synthesis pathway in Escherichia coli".

Authors :
Flower JE
Gibbons WJ Jr
Adams AM
Wang X
Broude CN
Jones JA
Source :
Biotechnology and bioengineering [Biotechnol Bioeng] 2023 Aug; Vol. 120 (8), pp. 2214-2229. Date of Electronic Publication: 2023 Jun 20.
Publication Year :
2023

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.<br /> (© 2023 The Authors. Biotechnology and Bioengineering published by Wiley Periodicals LLC.)

Details

Language :
English
ISSN :
1097-0290
Volume :
120
Issue :
8
Database :
MEDLINE
Journal :
Biotechnology and bioengineering
Publication Type :
Academic Journal
Accession number :
37337917
Full Text :
https://doi.org/10.1002/bit.28480