Work

Discovery, Biological Activity, and Biosynthesis of Pinocicolin A, an Antibiotic Isocyanide Metabolite Produced by Penicillium pinophilum

Year: 2025

Type: article

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.

Source: Journal of Natural Products

DOI: 10.1021/acs.jnatprod.5c00174

Authors: Shinji Kishimoto, Rikuto Takahashi, Akio Nagasawa, Kenji Watanabe

Institutions: Shizuoka University, University of Shizuoka

Language: English

Topic: Microbial Natural Products and Biosynthesis

Subfield: Pharmacology

Field: Medicine

Domain: Health Sciences

Open Access status: green

Funders: Uehara Memorial Foundation, Japan Agency for Medical Research and Development, Secom Science and Technology Foundation, Japan Society for the Promotion of Science