Iron acquisition in plague: modular logic in enzymatic biogenesis of yersiniabactin by Yersinia pestis
Iron acquisition in plague: modular logic in enzymatic biogenesis of yersiniabactin by Yersinia pestis
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DOI：
10.1016/s1074-5521(98)90115-6
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发表时间：
1998-10-01
影响因子：
--
通讯作者：
Perry, RD
中科院分区：
文献类型：
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作者：
Gehring, AM;DeMoll, E;Perry, RD
背景资料：鼠疫耶尔森氏菌（鼠疫耶尔森氏菌）是腺鼠疫的病原菌，其毒力与铁螯合铁载体耶尔森氏菌素（Yersiniabactin）的生物合成和运输有关，后者在铁饥饿条件下被诱导。初步的DNA测序表明，该系统是高度保守的致病性耶尔森氏菌。耶尔森菌素含有一个酚基和三个作为铁配体的五元噻唑杂环。鼠疫耶尔森氏杆菌的基因序列已被测定。耶尔森菌素生物合成区（irp 2-ybtE和ybtS）的序列分析揭示了使用HMWP 1和HMWP 2（由irp 1和irp 2编码）之间形成的混合聚酮合酶/非核糖体肽合成酶复合物生产铁载体的策略。该复合物含有16个结构域，其中5个是磷酸泛酰巯基乙胺修饰的肽基载体蛋白或酰基载体蛋白结构域的变体。HMWP 1和HMWP 2也含有甲基转移酶和杂环化结构域。突变的ybtS显示，该基因编码的蛋白质是必不可少的耶尔森氏菌素synthesis.Conclusions：HMWP 1和HMWP 2结构域的组织表明，耶尔森氏菌素铁载体组装在一个模块化的方式，其中一系列的共价中间体是通过从HMWP 2的氨基末端的HMWP 1的羧基末端。生物合成标记研究表明，三个耶尔森菌素甲基部分由S-腺苷甲硫氨酸提供，噻唑啉和噻唑烷环之间的接头来自丙二酰辅酶A。水杨酸部分可能是使用芳香族氨基酸生物合成途径合成的，其最后一步将分支酸盐转化为水杨酸盐。YbtS可能是将分支酸转化为水杨酸所必需的。
Background: Virulence in the pathogenic bacterium Yersinia pestis, causative agent of bubonic plague, has been correlated with the biosynthesis and transport of an iron-chelating siderophore, yersiniabactin, which is induced under iron-starvation conditions. Initial DNA sequencing suggested that this system is highly conserved among the pathogenic Yersinia. Yersiniabactin contains a phenolic group and three five-membered thiazole heterocycles that serve as iron ligands.Results: The entire Y. pestis yersiniabactin region has been sequenced. Sequence analysis of yersiniabactin biosynthetic regions (irp2-ybtE and ybtS) reveals a strategy for siderophore production using a mixed polyketide synthase/ nonribosomal peptide synthetase complex formed between HMWP1 and HMWP2 (encoded by irp1 and irp2). The complex contains 16 domains, five of them variants of phosphopantetheine-modified peptidyl carrier protein or acyl carrier protein domains. HMWP1 and HMWP2 also contain methyltransferase and heterocyclization domains. Mutating ybtS revealed that this gene encodes a protein essential for yersiniabactin synthesis.Conclusions: The HMWP1 and HMWP2 domain organization suggests that the yersiniabactin siderophore is assembled in a modular fashion; in which a series of covalent intermediates are passed from the amino terminus of HMWP2 to the carboxyl terminus of HMWP1. Biosynthetic labeling studies indicate that the three yersiniabactin methyl moieties are donated by S-adenosylmethionine and that the linker between the thiazoline and thiazolidine rings is derived from malonyl-CoA. The salicylate moiety is probably synthesized using the aromatic amino-acid biosynthetic pathway, the final step of which converts chorismate to salicylate. YbtS might be necessary for converting chorismate to salicylate.