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Eukaryotic Cell doi:10.1128/EC.00066-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

EstB-mediated hydrolysis of the siderophore triacetylfusarinine C optimizes iron uptake of Aspergillus fumigatus

Division of Molecular Biology and Division of Clinical Biochemistry, Biocenter, Innsbruck Medical University, Fritz-Pregl-Str. 3, A-6020 Innsbruck, Austria

^* To whom correspondence should be addressed. Email: hubertus.haas{at}i-med.ac.at.

	Abstract

Aspergillus fumigatus excretes the fusarinine-type siderophore desferri-triacetylfusarinine C (DF-TafC) to mobilize iron. DF-TafC is a cyclic peptide consisting of three N⁵-cis-anhydromevalonyl-N⁵-hydroxy-N²-acetyl-L-ornithine residues linked by ester bonds in contrast to peptide linkages found in ferrichrome-type siderophores. Subsequent to binding of iron and uptake, triacetylfusarinine C (TafC) is hydrolyzed, the cleavage products are excreted, and the iron is transferred to the metabolism or the intracellular siderophore desferri-ferricrocin (DF-FC) for iron storage.

Here we report the identification and characterization of the TafC-esterase EstB, the first eukaryotic siderophore-degrading enzyme. The encoding gene, estB, was found to be located in an iron-regulated gene cluster, indicating a role in iron metabolism. Deletion of estB in A. fumigatus eliminated TafC esterase activity of cellular extracts and caused increased intracellular accumulation of TafC and TafC hydrolysis products in vivo. Escherichia coli-expressed EstB displayed specific TafC-esterase activity but did not hydrolyze fusarinine C, which has the same core structure as TafC but lacks three N²-acetyl residues. Localization of EstB via enhanced green fluorescent protein (EGFP)-tagging suggested that TafC hydrolysis takes place in the cytoplasm. EstB abrogation reduced the intracellular transfer rate of iron from TafC to DF-FC and delayed iron sensing. Furthermore, EstB deficiency caused a decreased radial growth rate during iron depleted but not iron-replete conditions. Taken together, these data suggest that EstB-mediated TafC hydrolysis is not essential for but optimizes TafC-mediated iron uptake in A. fumigatus.