AUTHOR=Wiemann Philipp , Lechner Beatrix E. , Baccile Joshua A. , Velk Thomas A. , Yin Wen-Bing , Bok Jin Woo , Pakala Suman , Losada Liliana , Nierman William C. , Schroeder Frank C. , Haas Hubertus , Keller Nancy P. 

TITLE=Perturbations in small molecule synthesis uncovers an iron-responsive secondary metabolite network in Aspergillus fumigatus

JOURNAL=Frontiers in Microbiology

VOLUME=5

YEAR=2014

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2014.00530

DOI=10.3389/fmicb.2014.00530

ISSN=1664-302X

ABSTRACT=<p>Iron plays a critical role in survival and virulence of the opportunistic pathogen <italic>Aspergillus fumigatus</italic>. 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 <italic>A. fumigatus</italic> virulence. We found that HAS overproduction caused an iron starvation phenotype, from alteration of siderophore pools to regulation of iron homeostasis gene expression including <italic>sreA</italic>. 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.</p>