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Total Biosynthesis and Diverse Applications of the Nonribosomal Peptide-Polyketide Siderophore Yersiniabactin

机译:非核糖体肽-聚酮化合物铁载体耶尔西菌素的总生物合成和不同应用

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摘要

Yersiniabactin (Ybt) is a mixed nonribosomal peptide-polyketide natural product natively produced by the pathogen Yersinia pestis. The compound enables iron scavenging capabilities upon host infection and is biosynthesized by a nonribosomal peptide synthetase featuring a polyketide synthase module. This pathway has been engineered for expression and biosynthesis using Escherichia coli as a heterologous host. In the current work, the biosynthetic process for Ybt formation was improved through the incorporation of a dedicated step to eliminate the need for exogenous salicylate provision. When this improvement was made, the compound was tested in parallel applications that highlight the metal-chelating nature of the compound. In the first application, Ybt was assessed as a rust remover, demonstrating a capacity of ∼40% compared to a commercial removal agent and ∼20% relative to total removal capacity. The second application tested Ybt in removing copper from a variety of nonbiological and biological solution mixtures. Success across a variety of media indicates potential utility in diverse scenarios that include environmental and biomedical settings.
机译:耶尔森菌素(Yersiniabactin,Ybt)是由病原体鼠疫耶尔森氏菌天然产生的混合的非核糖体肽-聚酮化合物天然产物。该化合物可在宿主感染后实现铁清除能力,并通过具有聚酮化合物合酶模块特征的非核糖体肽合成酶进行生物合成。使用大肠杆菌作为异源宿主,已对该途径进行了表达和生物合成的工程改造。在当前的工作中,通过引入专用步骤消除了对外源水杨酸盐供应的需求,改善了Ybt形成的生物合成过程。进行此改进后,该化合物在平行应用中进行了测试,突出了该化合物的金属螯合性质。在第一个应用中,Ybt被评估为除锈剂,与商用除锈剂相比,除锈能力约为40%,相对于除锈能力约为20%。第二个应用程序测试了Ybt从各种非生物和生物溶液混合物中去除铜的能力。跨多种媒体的成功表明在包括环境和生物医学环境在内的各种场景中的潜在效用。

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