SidL, an Aspergillus fumigatus Transacetylase Involved in Biosynthesis of the Siderophores Ferricrocin and Hydroxyferricrocin
SidL, an Aspergillus fumigatus Transacetylase Involved in Biosynthesis of the Siderophores Ferricrocin and Hydroxyferricrocin
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DOI：
10.1128/aem.00182-11
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发表时间：
2011-07-01
影响因子：
4.4
通讯作者：
Haas, Hubertus
中科院分区：
文献类型：
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作者：
Blatzer, Michael;Schrettl, Markus;Haas, Hubertus
条件真菌病原体烟曲霉（Aspergillus fumigatus）产生四种类型的铁载体，即低分子质量铁螯合物：它分泌fusarinine C （FsC）和triacetylfusarinine C （TAFC）用于铁摄取，积累铁三聚氰胺（FC）用于菌丝和羟基铁三聚氰胺（HFC）用于分生孢子铁的分布和储存。铁载体的生物合成最近被证明对真菌的毒力至关重要。在这里，我们鉴定了真菌铁载体生物合成机制的一个新成分：AFUA_1G04450，称为SidL。SidL仅在产铁载体子囊菌中保守，与细菌铁载体生物合成中涉及的转酰基酶和TAFC生物合成所必需的N(5)-羟鸟氨酸：无氢甲氰酰基辅酶A-N(5)-转酰基酶SidF相似。烟曲霉体内SidL的失活降低了缺铁过程中FC的生物合成，完全阻断了富铁生长过程中FC的生物合成。与这些发现一致的是，SidL缺乏阻断了富铁条件下fc来源的HFC的孢子积累，从而延迟了孢子的萌发，降低了孢子的大小，降低了孢子对氧化应激的抵抗力。值得注意的是，sidL基因不与其他铁载体生物合成基因聚集，其表达不受铁可利用性的影响。用增强的绿色荧光蛋白标记SidL表明fc -生物合成机制的细胞质定位。综上所述，这些数据表明，SidL是FC生物合成所需的组成活性N(5)-羟氨酸-乙酰化酶，特别是在富含铁的条件下。此外，这项研究揭示了铁载体生物合成的意想不到的复杂性，表明存在另一种铁抑制的N(5)-羟鸟氨酸乙酰化酶。
The opportunistic fungal pathogen Aspergillus fumigatus produces four types of siderophores, low-molecular-mass iron chelators: it excretes fusarinine C (FsC) and triacetylfusarinine C (TAFC) for iron uptake and accumulates ferricrocin (FC) for hyphal and hydroxyferricrocin (HFC) for conidial iron distribution and storage. Siderophore biosynthesis has recently been shown to be crucial for fungal virulence. Here we identified a new component of the fungal siderophore biosynthetic machinery: AFUA_1G04450, termed SidL. SidL is conserved only in siderophore-producing ascomycetes and shows similarity to transacylases involved in bacterial siderophore biosynthesis and the N(5)-hydroxyornithine: anhydromevalonyl coenzyme A-N(5)-transacylase SidF, which is essential for TAFC biosynthesis. Inactivation of SidL in A. fumigatus decreased FC biosynthesis during iron starvation and completely blocked FC biosynthesis during iron-replete growth. In agreement with these findings, SidL deficiency blocked conidial accumulation of FC-derived HFC under iron-replete conditions, which delayed germination and decreased the size of conidia and their resistance to oxidative stress. Remarkably, the sidL gene is not clustered with other siderophore-biosynthetic genes, and its expression is not affected by iron availability. Tagging of SidL with enhanced green fluorescent protein suggested a cytosolic localization of the FC-biosynthetic machinery. Taken together, these data suggest that SidL is a constitutively active N(5)-hydroxyornithine-acetylase required for FC biosynthesis, in particular under iron-replete conditions. Moreover, this study revealed the unexpected complexity of siderophore biosynthesis, indicating the existence of an additional, iron-repressed N(5)-hydroxyornithine-acetylase.