SREA is involved in regulation of siderophore biosynthesis, utilization and uptake in Aspergillus nidulans

Under conditions of low iron availability, most fungi excrete siderophores. in order to mobilize extracellular iron. We show that lack of the GATA-typ e transcription factor SREA in Aspergillus nidulans not only leads to derep ression of siderophore biosynthesis but also to deregulation of siderophore -bound iron uptake and ornithine esterase expression. Furthermore, SREA def iciency causes increased accumulation of ferricrocin, the siderophore respo nsible for intracellular iron storage. In sreA deletion strains, extracellu lar siderophore production is derepressed but still regulated negatively by iron availability, indicating the presence of an additional iron-regulator y mechanism. In contrast, iron affects ferricrocin accumulation in a positi ve way, suggesting a protective role for this siderophore in detoxification of intracellular iron excess. The harmfulness of deregulated iron uptake i n this mutant is demonstrated by increased expression of genes encoding the antioxidative enzymes catalase CATB and the superoxide dismutases, SODA an d SODB. It is noteworthy that iron starvation was found to repress catB exp ression in wild-type (wt) and SREA-deficient strains, consistent with catB being subject to SREA-independent iron regulation. Differential display led to the identification of putative SREA target genes amcA and mirA. The ded uced MIRA amino acid sequence displays significant similarity to recently c haracterized siderophore permeases of Saccharomyces cerevisiae. amcA encode s a putative mitochondrial carrier for the siderophore precursor ornithine, indicating cross-regulation of siderophore and ornithine metabolism.