气候变化领域集成服务门户(CCPortal): Dual-purpose isocyanides produced by Aspergillus fumigatus contribute to cellular copper sufficiency and exhibit antimicrobial activity

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DOI	10.1073/pnas.2015224118
	Dual-purpose isocyanides produced by Aspergillus fumigatus contribute to cellular copper sufficiency and exhibit antimicrobial activity
	Raffa N.; Won T.H.; Sukowaty A.; Candor K.; Cui C.; Halder S.; Dai M.; Landero-Figueroa J.A.; Schroeder F.C.; Keller N.P.
发表日期	2021
ISSN	00278424
卷号	118 期号:8
英文摘要	The maintenance of sufficient but nontoxic pools of metal micro-nutrients 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 in fungi. Here we demonstrate that, in Aspergillus fumigatus, xanthocillin and other isocyanides derived from the xan biosynthetic gene cluster (BGC) bind copper, impact cellular copper content, and have significant metal-dependent antimicrobial properties. xan BGC-derived isocyanides are secreted and bind copper as visualized by a chrome azurol S (CAS) assay, and inductively coupled plasma mass spectrometry analysis of A. fumigatus intracellular copper pools demonstrated a role for xan cluster metabolites in the accumulation of copper. A. fumigatus coculture with a variety of human pathogenic fungi and bacteria established copper-dependent antimicrobial properties of xan BGC metabolites, including inhibition of laccase activity. Remediation of xanthocillin-treated Pseudomonas aeruginosa growth by copper supported the copper-chelating properties of xan BGC isocyanide products. The existence of the xan BGC in several filamentous fungi suggests a heretofore unknown role of eukaryotic natural products in copper homeostasis and mediation of interactions with competing microbes. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Aspergillus; Chalkophore; Copper; Fungi; Isocyanide
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180593
作者单位	Department of Medical Microbiology and Immunology, University of Wisconsin–Madison, Madison, WI 53706, United States; Boyce Thompson Institute, Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, United States; Agilent Metallomics Center of the Americas, Department of Chemistry, University of Cincinnati College of Arts and Science, Cincinnati, OH 45221, United States; Department of Chemistry and Center for Cancer Research, Purdue University, West Lafayette, IN 47906, United States; Department of Pharmacology and System Biology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, United States; Department of Bacteriology, University of Wisconsin–Madison, Madison, WI 53706, United States
推荐引用方式 GB/T 7714	Raffa N.,Won T.H.,Sukowaty A.,et al. Dual-purpose isocyanides produced by Aspergillus fumigatus contribute to cellular copper sufficiency and exhibit antimicrobial activity[J],2021,118(8).
APA	Raffa N..,Won T.H..,Sukowaty A..,Candor K..,Cui C..,...&Keller N.P..(2021).Dual-purpose isocyanides produced by Aspergillus fumigatus contribute to cellular copper sufficiency and exhibit antimicrobial activity.Proceedings of the National Academy of Sciences of the United States of America,118(8).
MLA	Raffa N.,et al."Dual-purpose isocyanides produced by Aspergillus fumigatus contribute to cellular copper sufficiency and exhibit antimicrobial activity".Proceedings of the National Academy of Sciences of the United States of America 118.8(2021).