Siderophores are a structurally diverse class of natural products common to most bacteria and fungi as iron(III)-chelating ligands. Siderophores, including trihydroxamate ferrioxamines, are used clinically to treat iron overload diseases and show promising activity against many other iron-related human diseases. Here, we present a new method for the isolation of ferrioxamine siderophores from complex mixtures using affinity chromatography based on resin-immobilized FhuD2, a siderophore-binding protein (SBP) from Staphylococcus aureus. The SBP-resin enabled purification of charge positive, charge negative, and neutral ferrioxamine siderophores. Treatment of culture supernatants from Streptomyces violaceus DSM 8286 with SBP-resin provided an analytically pure sample of the salmycins, a mixture of structurally complex glycosylated sideromycins (siderophore–antibiotic conjugates) with potent antibacterial activity toward human pathogenic Staphylococcus aureus (minimum inhibitory concentration (MIC) = 7 nM). Siderophore affinity chromatography could enable the rapid discovery of new siderophore and sideromycin natural products from complex mixtures to aid drug discovery and metabolite identification efforts in a broad range of therapeutic areas.

中文翻译：

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固定化的FhuD2铁载体结合蛋白能够从紫链霉菌DSM 8286纯化沙门菌素铁霉素

铁载体是大多数细菌和真菌中常见的铁（III）螯合配体，在结构上是一类天然产物。铁载体，包括三羟肟酸亚铁胺，在临床上用于治疗铁超负荷疾病，并显示出对许多其他与铁有关的人类疾病的有希望的活性。在这里，我们提出了一种新方法，该方法使用基于树脂固定的FhuD2（一种来自金黄色葡萄球菌的铁载体结合蛋白（SBP））的亲和色谱法，从复杂混合物中分离出亚铁胺铁载体。SBP树脂可纯化正电荷，负电荷和中性亚铁氧铁铁载体。紫链霉菌培养上清液的处理带有SBP树脂的DSM 8286提供了分析纯的沙门氏菌样品，这是结构复杂的糖基化铁霉素（铁载体－抗生素结合物）的混合物，对人病原性金黄色葡萄球菌具有有效的抗菌活性（最低抑菌浓度（MIC）= 7 nM）。铁载体亲和色谱可以从复杂的混合物中快速发现新的铁载体和铁霉素天然产物，从而有助于在广泛的治疗领域中进行药物发现和代谢物鉴定。