Iron-Dependent Remodeling of Fungal Metabolic Pathways Associated with Ferrichrome Biosynthesis
Iron-Dependent Remodeling of Fungal Metabolic Pathways Associated with Ferrichrome Biosynthesis
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DOI：
10.1128/aem.00659-10
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发表时间：
2010-06-01
影响因子：
4.4
通讯作者：
Labbe, Simon
中科院分区：
文献类型：
--
作者：
Mercier, Alexandre;Labbe, Simon
裂殖酵母粟酒裂殖酵母分泌并积累异羟肟酸盐型铁载体铁色素。sib 1（+）和sib 2（+）基因分别编码参与铁色素生物合成的铁载体合成酶和L-鸟氨酸N-5-加氧酶。在本报告中，我们证明sib 1（+）和sib 2（+）的抑制GATA型转录抑制因子Fep 1在高水平的铁。我们进一步发现，Fep 1的损失导致铁色素产量增加。我们发现，一个sib 1三角洲sib 2三角洲突变株表现出严重的生长缺陷铁贫媒体。我们确定了两种代谢途径参与了鸟氨酸的生物合成，鸟氨酸是铁色素的一种必需前体。精氨酸被Car 1和Car 3蛋白水解产生鸟氨酸。尽管car 3（+）是组成型表达的，但在暴露于铁时，car 1（+）转录水平被抑制，伴随着Car 1脱氢酶活性的降低。鸟氨酸也是通过谷氨酸的转化产生的，谷氨酸本身是通过两个独立的生物合成途径产生的，这两个途径由铁以相反的方式进行转录调节。在一个途径中，谷氨酸脱氢酶Gdh 1，从2-酮戊二酸产生谷氨酸，在铁充足的条件下，以Fep 1依赖的方式被抑制。另一个途径涉及两个耦合的酶，谷氨酰胺合成酶Gln 1和含Fe-S簇的谷氨酸合酶Glt 1，这两个酶在铁限制条件下被抑制，但在铁充足的条件下表达。总的来说，这些结果表明，在缺铁的条件下，酵母重塑与铁色素合成相关的代谢途径，以限制铁的利用，而不影响铁载体的生产及其从环境中螯合铁的能力。
The fission yeast Schizosaccharomyces pombe excretes and accumulates the hydroxamate-type siderophore ferrichrome. The sib1(+) and sib2(+) genes encode, respectively, a siderophore synthetase and an L-ornithine N-5-oxygenase that participate in ferrichrome biosynthesis. In the present report, we demonstrate that sib1(+) and sib2(+) are repressed by the GATA-type transcriptional repressor Fep1 in response to high levels of iron. We further found that the loss of Fep1 results in increased ferrichrome production. We showed that a sib1 Delta sib2 Delta mutant strain exhibits a severe growth defect on iron-poor media. We determined that two metabolic pathways are involved in biosynthesis of ornithine, an obligatory precursor of ferrichrome. Ornithine is produced by hydrolysis of arginine by the Car1 and Car3 proteins. Although car3(+) was constitutively expressed, car1(+) transcription levels were repressed upon exposure to iron, with a concomitant decrease of Car1 arginase activity. Ornithine is also generated by transformation of glutamate, which itself is produced by two separate biosynthetic pathways which are transcriptionally regulated by iron in an opposite fashion. In one pathway, the glutamate dehydrogenase Gdh1, which produces glutamate from 2-ketoglutarate, was repressed under iron-replete conditions in a Fep1-dependent manner. The other pathway involves two coupled enzymes, glutamine synthetase Gln1 and Fe-S cluster-containing glutamate synthase Glt1, which were both repressed under iron-limiting conditions but were expressed under iron-replete conditions. Collectively, these results indicate that under conditions of iron deprivation, yeast remodels metabolic pathways linked to ferrichrome synthesis in order to limit iron utilization without compromising siderophore production and its ability to sequester iron from the environment.