Tags

Type your tag names separated by a space and hit enter

Perturbations in small molecule synthesis uncovers an iron-responsive secondary metabolite network in Aspergillus fumigatus.
Front Microbiol 2014; 5:530FM

Abstract

Iron plays a critical role in survival and virulence of the opportunistic pathogen Aspergillus fumigatus. Two transcription factors, the GATA-factor SreA and the bZip-factor HapX oppositely monitor iron homeostasis with HapX activating iron acquisition pathways (e.g., siderophores) and shutting down iron consumptive pathways (and SreA) during iron starvation conditions whereas SreA negatively regulates HapX and corresponding pathways during iron sufficiency. Recently the non-ribosomal peptide, hexadehydroastechrome (HAS; a tryptophan-derived iron (III)-complex), has been found important in A. fumigatus virulence. We found that HAS overproduction caused an iron starvation phenotype, from alteration of siderophore pools to regulation of iron homeostasis gene expression including sreA. Moreover, we uncovered an iron dependent secondary metabolism network where both SreA and HapX oppositely regulate multiple other secondary metabolites including HAS. This circuitry links iron-acquisition and consumption pathways with secondary metabolism-thus placing HAS as part of a metabolic feedback circuitry designed to balance iron pools in the fungus and presenting iron availability as one environmental trigger of secondary metabolism.

Authors+Show Affiliations

Department of Medical Microbiology and Immunology, University of Wisconsin-Madison Madison, WI, USA.Division of Molecular Biology/Biocenter, Innsbruck Medical University Innsbruck, Austria.Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University Ithaca, NY, USA.Department of Medical Microbiology and Immunology, University of Wisconsin-Madison Madison, WI, USA.Department of Medical Microbiology and Immunology, University of Wisconsin-Madison Madison, WI, USA.Department of Medical Microbiology and Immunology, University of Wisconsin-Madison Madison, WI, USA.The J. Craig Venter Institute Rockville, MD, USA.The J. Craig Venter Institute Rockville, MD, USA.The J. Craig Venter Institute Rockville, MD, USA.Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University Ithaca, NY, USA.Division of Molecular Biology/Biocenter, Innsbruck Medical University Innsbruck, Austria.Department of Medical Microbiology and Immunology, University of Wisconsin-Madison Madison, WI, USA ; Department of Bacteriology, University of Wisconsin-Madison Madison, WI, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

25386169

Citation

Wiemann, Philipp, et al. "Perturbations in Small Molecule Synthesis Uncovers an Iron-responsive Secondary Metabolite Network in Aspergillus Fumigatus." Frontiers in Microbiology, vol. 5, 2014, p. 530.
Wiemann P, Lechner BE, Baccile JA, et al. Perturbations in small molecule synthesis uncovers an iron-responsive secondary metabolite network in Aspergillus fumigatus. Front Microbiol. 2014;5:530.
Wiemann, P., Lechner, B. E., Baccile, J. A., Velk, T. A., Yin, W. B., Bok, J. W., ... Keller, N. P. (2014). Perturbations in small molecule synthesis uncovers an iron-responsive secondary metabolite network in Aspergillus fumigatus. Frontiers in Microbiology, 5, p. 530. doi:10.3389/fmicb.2014.00530.
Wiemann P, et al. Perturbations in Small Molecule Synthesis Uncovers an Iron-responsive Secondary Metabolite Network in Aspergillus Fumigatus. Front Microbiol. 2014;5:530. PubMed PMID: 25386169.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Perturbations in small molecule synthesis uncovers an iron-responsive secondary metabolite network in Aspergillus fumigatus. AU - Wiemann,Philipp, AU - Lechner,Beatrix E, AU - Baccile,Joshua A, AU - Velk,Thomas A, AU - Yin,Wen-Bing, AU - Bok,Jin Woo, AU - Pakala,Suman, AU - Losada,Liliana, AU - Nierman,William C, AU - Schroeder,Frank C, AU - Haas,Hubertus, AU - Keller,Nancy P, Y1 - 2014/10/24/ PY - 2014/07/11/received PY - 2014/09/23/accepted PY - 2014/11/12/entrez PY - 2014/11/12/pubmed PY - 2014/11/12/medline KW - Aspergillus fumigatus KW - HapX KW - SreA KW - gene regulation KW - hexadehydroastechrome KW - iron KW - secondary metabolism SP - 530 EP - 530 JF - Frontiers in microbiology JO - Front Microbiol VL - 5 N2 - Iron plays a critical role in survival and virulence of the opportunistic pathogen Aspergillus fumigatus. Two transcription factors, the GATA-factor SreA and the bZip-factor HapX oppositely monitor iron homeostasis with HapX activating iron acquisition pathways (e.g., siderophores) and shutting down iron consumptive pathways (and SreA) during iron starvation conditions whereas SreA negatively regulates HapX and corresponding pathways during iron sufficiency. Recently the non-ribosomal peptide, hexadehydroastechrome (HAS; a tryptophan-derived iron (III)-complex), has been found important in A. fumigatus virulence. We found that HAS overproduction caused an iron starvation phenotype, from alteration of siderophore pools to regulation of iron homeostasis gene expression including sreA. Moreover, we uncovered an iron dependent secondary metabolism network where both SreA and HapX oppositely regulate multiple other secondary metabolites including HAS. This circuitry links iron-acquisition and consumption pathways with secondary metabolism-thus placing HAS as part of a metabolic feedback circuitry designed to balance iron pools in the fungus and presenting iron availability as one environmental trigger of secondary metabolism. SN - 1664-302X UR - https://www.unboundmedicine.com/medline/citation/25386169/Perturbations_in_small_molecule_synthesis_uncovers_an_iron_responsive_secondary_metabolite_network_in_Aspergillus_fumigatus_ L2 - https://dx.doi.org/10.3389/fmicb.2014.00530 DB - PRIME DP - Unbound Medicine ER -