Virtually all organisms require iron as indispensable cofactor for various metabolic processes. The opportunistic fungal pathogen Aspergillus fumigatus produces two major siderophores (low molecular-mass ferric iron chelators): it excretes triacetylfusarinine C for iron uptake and accumulates ferricrocin for intracellular iron storage. Biosynthesis of both triacetylfusarinine C and ferricrocin has previously been shown to be crucial for virulence of A. fumigatus. Here, we report the functional characterization of a new component of the fungal siderophore biosynthetic machinery Afu1g04450, termed SidL. SidL is conserved in siderophore-producing but not non-siderophore producing ascomycetes. The C-terminal half of SidL shows similarity to acetylases involved in bacterial siderophore biosynthesis, e.g. Escherichia coli IucB (a hydroxylysine acetylase required for aerobactin biosynthesis) and PvdY (a hydroxyornithine acetylase required for pyoverdin biosynthesis), and the hydroxyornithine:anhydromevalonyl coenzyme A-transacylase SidF that is essential for triacetylfusarine C biosynthesis. Deletion of sidL in A. fumigatus reduced ferricrocin biosynthesis during iron starvation and blocked ferricirocin biosynthesis during iron-replete growth. Furthermore, sidL-deficiency blocked conidial ferricrocin accumulation under strict iron-replete conditions but not when mycelia were transferred from iron-depleted to iron-replete conditions before sporulation. In contrast, SidL-deficiency had no effect on triacetylfusarinine C production. The expression of sidL was affected neither by iron availability nor the iron regulator SreA. Taken together, these data show that SidL is a constitutively expressed hydroxyornithine acetylase involved in ferricrocin biosynthesis. Moreover, the data indicate the existence of a second hydroxyornithine acetylase, the activity of which is induced by iron starvation. This study identified a novel component of the fungal siderophore biosynthetic machinery and revealed unexpected complexity.
Full conference title:
10th EUROPEAN CONFERENCE ON FUNGAL GENETICS
- ECFG 10th (2010)