RRC ID 88974
Author Kishimoto S, Takahashi R, Nagasawa A, Watanabe K.
Title Discovery, Biological Activity, and Biosynthesis of Pinocicolin A, an Antibiotic Isocyanide Metabolite Produced by Penicillium pinophilum.
Journal J Nat Prod
Abstract We discovered new natural products pinocicolins A (1) and B (2) from Penicillium pinophilum and determined the stereochemistry of these compounds by degradation and derivatization. Compound 1, containing two isocyanide groups, exhibited bacteriostatic activity against Gram-positive bacteria depending upon its copper-chelating activity. The biosynthesis of compound 1 was reconstructed in Aspergillus nidulans by heterologous expression of multidomain isocyanide synthase-nonribosomal peptide synthetase Pp_crmA and efflux pump Pp_crmE. This is the first report of the heterologous production of a fungal diisocyanide natural product, highlighting the multistep catalysis of CrmA family enzymes.
Volume 88(4)
Pages 1068-1074
Published 2025-4-25
DOI 10.1021/acs.jnatprod.5c00174
PMID 40180616
MeSH Anti-Bacterial Agents* / biosynthesis Anti-Bacterial Agents* / chemistry Anti-Bacterial Agents* / isolation & purification Anti-Bacterial Agents* / pharmacology Aspergillus nidulans / genetics Aspergillus nidulans / metabolism Cyanides* / chemistry Cyanides* / metabolism Cyanides* / pharmacology Gram-Positive Bacteria / drug effects Microbial Sensitivity Tests Molecular Structure Penicillium* / chemistry Penicillium* / metabolism Peptide Synthases / metabolism
Resource
General Microbes JCM23043