Dual-purpose isocyanides produced by Aspergillus fumigatus contribute to cellular copper sufficiency and exhibit antimicrobial activity

• DOI: 10.1073/pnas.2015224118
• Publication Date: 2021-02-16T21:49:37Z
• Authors: Nicholas Raffa; Tae Hyung Won; Andrew Sukowaty; Kathleen Candor; Chengsen Cui; Saayak Halder; Mingji Dai; Julio A. Landero-...; Frank C. Schroeder; Nancy P. Keller
• Keywords: 0301 basic medicine; 0303 health sciences; Cyanides; Pigmentation; Aspergillus fumigatus; Laccase; Microbial Sensitivity Tests; Spores, Fungal; Aspergillus nidulans; Fungal Proteins; 03 medical and health sciences; Anti-Infective Agents; Phenols; Gene Expression Regulation, Fungal; Multigene Family; Mutation; Butadienes; Copper; Gene Deletion

The maintenance of sufficient but nontoxic pools metal micronutrients is accomplished through diverse homeostasis mechanisms in fungi. Siderophores play a well established role for iron homeostasis; however, no copper-binding analogs have been found Here we demonstrate that, Aspergillus fumigatus, xanthocillin and other isocyanides derived from the xan biosynthetic gene cluster (BGC) bind copper, impact cellular copper content, significant metal-dependent antimicrobial properties. BGC-derived are secreted as visualized by chrome azurol S (CAS) assay, inductively coupled plasma mass spectrometry analysis A. fumigatus intracellular demonstrated metabolites accumulation copper. coculture with variety human pathogenic fungi bacteria copper-dependent properties BGC metabolites, including inhibition laccase activity. Remediation xanthocillin-treated Pseudomonas aeruginosa growth supported copper-chelating isocyanide products. existence several filamentous suggests heretofore unknown eukaryotic natural products mediation interactions competing microbes.