Identification of Nocobactin NA Biosynthetic Gene Clusters in Nocardia farcinica
Identification of Nocobactin NA Biosynthetic Gene Clusters in Nocardia farcinica
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DOI：
10.1128/jb.00897-10
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发表时间：
2011-01-01
影响因子：
3.2
通讯作者：
Ishikawa, Jun
中科院分区：
文献类型：
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作者：
Hoshino, Yasutaka;Chiba, Kazuhiro;Ishikawa, Jun
我们确定了铁载体nocobactin NA的生物合成基因簇。通过对Nocardia farcinica IFM 10152的基因组测序发现，作为与分枝杆菌素生物合成基因高度同源的基因的nbt簇由分别位于两个基因组区域的10个基因组成。的基因组织的nbt集群和预测的功能的nbt基因，特别是环化和差向异构化结构域，是在良好的协议与nocobactin NA的化学结构。破坏的nbtA和nbtE基因，分别减少和废除nocobactin NA的生产力。nbtS基因的异源表达揭示了该基因编码水杨酸合酶。这些结果表明nbt簇负责诺可肌动蛋白NA的生物合成。我们还发现推定的IdeR结合序列上游的nbtA，G，H，S和T基因，其表达是10倍以上，在低铁条件下比高铁条件。这些结果表明，nbt基因的协调调节IdeR蛋白在铁依赖性的方式。发现Δ nbtE突变体对J774A.1细胞的细胞毒性受损，表明N.闹剧
We identified the biosynthetic gene clusters of the siderophore nocobactin NA. The nbt clusters, which were discovered as genes highly homologous to the mycobactin biosynthesis genes by the genomic sequencing of Nocardia farcinica IFM 10152, consist of 10 genes separately located at two genomic regions. The gene organization of the nbt clusters and the predicted functions of the nbt genes, particularly the cyclization and epimerization domains, were in good agreement with the chemical structure of nocobactin NA. Disruptions of the nbtA and nbtE genes, respectively, reduced and abolished the productivity of nocobactin NA. The heterologous expression of the nbtS gene revealed that this gene encoded a salicylate synthase. These results indicate that the nbt clusters are responsible for the biosynthesis of nocobactin NA. We also found putative IdeR-binding sequences upstream of the nbtA, -G, -H, -S, and -T genes, whose expression was more than 10-fold higher in the low-iron condition than in the high-iron condition. These results suggest that nbt genes are regulated coordinately by IdeR protein in an iron-dependent manner. The Delta nbtE mutant was found to be impaired in cytotoxicity against J774A.1 cells, suggesting that nocobactin NA production is required for virulence of N. farcinica.