title: Mycofumigation through production of the volatile DNA-methylating agentN-methyl-N-nitrosoisobutyramide by fungi in the genusMuscodor.
abstract: Antagonistic microorganisms produce antimicrobials to inhibit the growth of competitors. Although water-soluble antimicrobials are limited to proximal interactions via aqueous diffusion, volatile antimicrobials are able to act at a distance and diffuse through heterogeneous environments. Here, we identify the mechanism of action ofMuscodor albus, an endophytic fungus known for its volatile antimicrobial activity toward a wide range of human and plant pathogens and its potential use in mycofumigation. Proposed uses of theMuscodorspecies include protecting crops, produce, and building materials from undesired fungal or bacterial growth. By analyzing a collection ofMuscodorisolates with varying toxicity, we demonstrate that the volatile mycotoxin,N-methyl-N-nitrosoisobutyramide, is the dominant factor inMuscodortoxicity and acts primarily through DNA methylation. Additionally,Muscodorisolates exhibit higher resistance to DNA methylation compared with other fungi. This work contributes to the evaluation ofMuscodorisolates as potential mycofumigants, provides insight into chemical strategies that organisms use to manipulate their environment, and provokes questions regarding the mechanisms of resistance used to tolerate constitutive, long-term exposure to DNA methylation.
authors.affiliation: From the Departments of Chemistry and.
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Hutchings
authors.affiliation: Molecular Biophysics and Biochemistry, Chemical Biology Institute, and.
authors.forename: Cambria J
authors.initials: CJ
authors.lastname: Alpha-Cobb
authors.affiliation: Molecular Biophysics and Biochemistry, Chemical Biology Institute, and.
authors.forename: David A
authors.initials: DA
authors.lastname: Hiller
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Nanobiology Institute, Yale University, West Haven, Connecticut 06516.
authors.forename: Julien
authors.initials: J
authors.lastname: Berro
authors.affiliation: Molecular Biophysics and Biochemistry, Chemical Biology Institute, and scott.strobel@yale.edu.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Strobel
mesh_terms: D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology; D019175:DNA Methylation / Q000187:drug effects*; D004271:DNA, Fungal / Q000378:metabolism*; D025141:Drug Resistance, Fungal / Q000187:drug effects*; D006801:Humans; D008745:Methylation; D055549:Volatile Organic Compounds / Q000737:chemistry / Q000494:pharmacology; D013098:Xylariales / Q000378:metabolism*
chemical_list: D000935:Antifungal Agents; D004271:DNA, Fungal; D055549:Volatile Organic Compounds
keywords: DNA methylation; N-nitroso compounds; cell death; endophyte; fungi; gas chromatography-mass spectrometry (GC-MS); mycofumigation; mycotoxin; toxicity; volatile organic compounds