Structural Characterization of the Heterobactin Siderophores from Rhodococcus erythropolis PR4 and Elucidation of Their Biosynthetic Machinery
Structural Characterization of the Heterobactin Siderophores from Rhodococcus erythropolis PR4 and Elucidation of Their Biosynthetic Machinery
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DOI：
10.1021/np4006579
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发表时间：
2013-12-01
影响因子：
5.1
通讯作者：
Marahiel, Mohamed A.
中科院分区：
文献类型：
--
作者：
Bosello, Mattia;Zeyadi, Mustafa;Marahiel, Mohamed A.
本研究报道了红球红球菌PR4中异结合蛋白的分离、结构特征及其生物合成来源。通过MSN分析和核磁共振谱对杂多菌素A的结构进行了分析，发现精氨酸残基的胍基和2，3-二羟基苯甲酸酯部分之间存在一个值得注意的肽键。这两个异构体S1和S2是异构体A的衍生物，它们在芳环上具有磺化修饰。对红球藻PR4基因组的生物信息学分析以及随后对可能的生物合成机制的遗传和生化特征进行了鉴定，确定了负责异结合蛋白生物合成的基因簇。有趣的是，HtbG NRPS在合成酶的第二模块中呈现出前所未有的C-PCP-A结构域组织，这可能有助于肽中间体的正确延伸。最后，本工作对Carrano等人描述的异构体A的结构进行了修正。在2001年。
In this study, the isolation, the structural characterization, and the elucidation of the biosynthetic origin of heterobactins, catecholate-hydroxamate mixed-type siderophores from Rhodococcus erythropolis PR4, are reported. The structure elucidation of heterobactin A was accomplished via MSn analysis and NMR spectroscopy and revealed the noteworthy presence of a peptide bond between the guanidine group of an arginine residue and a 2,3-dihydroxybenzoate moiety. The two heterobactin S1 and S2 variants are derivatives of heterobactin A that have sulfonation modifications on the aromatic rings. The bioinformatic analysis of the R. erythropolis PR4 genome and the subsequent genetic and biochemical characterization of the putative biosynthetic machinery identified the gene cluster responsible for the biosynthesis of the heterobactins. Interestingly, the HtbG NRPS presents an unprecedented C-PCP-A domain organization within the second module of the synthetase that may help the correct elongation of the peptide intermediate. Finally, the present work revises the structure of heterobactin A that was described by Carrano et al. in 2001.