PXD061303

PXD061303 is an original dataset announced via ProteomeXchange.

Title	In Vitro Psilocybin Synthesis by Co-Immobilized Enzymes
Description	Advanced clinical trials investigate the Psilocybe magic mushroom natural product psilocybin as a treatment against major depressive disorder. Currently, synthetic material is used to meet the demand for legitimate pharmaceutical purposes. Here, we report an in vitro approach to biocatalytically produce psilocybin on a solid-phase matrix charged with five covalently bound biosynthetic enzymes. These enzymes include three Psilocybe enzymes: IasA, an engineered L-tryptophan decarboxylase/aromatic aldehyde synthase, the 4-hydroxytryptamine kinase PsiK and the norbaeocystin methyltransferase PsiM, along with Escherichia coli nucleosidase MtnN and adenine deaminase Ade. In a proof-of-principle experiment, this enzyme-charged resin allowed for quantitative turnover of 4-hydroxy-L-tryptophan into psilocybin. This facile process i) represents a sustainable approach with reusable enzymes, ii) circumvents the drawbacks of in vivo processes while harnessing the selectivity of enzymatic catalysis and iii) helps access an urgently needed drug candidate.
HostingRepository	PRIDE
AnnounceDate	2025-05-05
AnnouncementXML	Submission_2025-05-05_03:09:07.581.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Thomas Krüger
SpeciesList	scientific name: Escherichia coli; NCBI TaxID: 562; scientific name: Psilocybe sp. 180; NCBI TaxID: 1617910;
ModificationList	phosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2025-02-28 06:10:26	ID requested
⏵ 1	2025-05-05 03:09:08	announced

Sch, ä, fer T, Sherwood A, Kirkland T, Kr, ü, ger T, Worbs J, Kniemeyer O, Gressler M, Hoffmeister D, In Vitro Psilocybin Synthesis by Co-Immobilized Enzymes. Chemistry, 31(29):e202501037(2025) [pubmed]

10.1002/chem.202501037;

submitter keyword: biosynthesis, mushrooms, LC-MS,Psilocybin, in vitro synthesis

Axel Brakhage
contact affiliation	Department for Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Leibniz-HKI, Jena
contact email	axel.brakhage@leibniz-hki.de
lab head
Thomas Krüger
contact affiliation	Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute
contact email	thomas.krueger@leibniz-hki.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD061303
     1. Label: PRIDE project
     2. Name: In Vitro Psilocybin Synthesis by Co-Immobilized Enzymes