Plasticity of the Malleobactin Pathway and Its Impact on Siderophore Action in Human Pathogenic Bacteria
Plasticity of the Malleobactin Pathway and Its Impact on Siderophore Action in Human Pathogenic Bacteria
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DOI：
10.1002/chem.201500757
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发表时间：
2015-05-26
影响因子：
4.3
通讯作者：
Hertweck, Christian
中科院分区：
文献类型：
--
作者：
Franke, Jakob;Ishida, Keishi;Hertweck, Christian
人类致病菌鼻疽伯克霍尔德氏菌、伪鼻疽伯克霍尔德氏菌和泰国伯克霍尔德氏菌拥有高度保守的基因簇，编码长期以来备受追捧的槌杆菌素的生物合成。本研究中分离并充分表征了 Malleobactin 家族的四种新的、意想不到的同系物，其特征是与亲本鸟球菌素样结构存在不寻常的偏差。因此，malleobactin 非核糖体肽合成酶 (NRPS) 具有罕见的灵活性，可产生多种肽骨架，其中一种候选酶具有显着的铁载体活性（EC50：8.4M，CAS 测定）。这些发现不仅揭示了高度多样化的装配线，而且是对病原体代谢组知识库的重要补充。
The human pathogenic bacteria Burkholderia mallei, Burkholderia pseudomallei, and Burkholderia thailandensis harbor a highly conserved gene cluster coding for the biosynthesis of the long sought-after malleobactins. Four new, unexpected congeners of the malleobactin family that were isolated and fully characterized in this study feature unusual deviations from the parent, ornibactin-like architecture. Thus, the malleobactin non-ribosomal peptide synthetase (NRPS) has a rare flexibility that yields diverse peptide backbones, of which one candidate confers pronounced siderophore activity (EC50: 8.4M, CAS assay). These findings not only unveil a highly diverse assembly line but also are an important addition to the knowledgebase of the pathogens' metabolomes.