Actinobacteria have been a rich source of novel, structurally complex natural products for many decades. Although the largest genus is Streptomyces, from which the majority of antibiotics in current and past clinical use were originally isolated, other less common genera also have the potential to produce a wealth of novel secondary metabolites. One example is the Kutzneria genus, which currently contains only five reported species. One of these species is Kutzneria albida DSM 43870T, which has 46 predicted biosynthetic gene clusters and is known to produce the macrolide antibiotic aculeximycin. Here, we report the isolation and structural characterization of two novel 30-membered glycosylated macrolides, epemicins A and B, that are structurally related to aculeximycin, from a rare Kutzneria sp. The absolute configuration for all chiral centers in the two compounds is proposed based on extensive 1D and 2D NMR studies and bioinformatics analysis of the gene cluster. Through heterologous expression and genetic inactivation, we have confirmed the link between the biosynthetic gene cluster and the new molecules. These findings show the potential of rare Actinobacteria to produce new, structurally diverse metabolites. Furthermore, the gene inactivation represents the first published report to genetically manipulate a representative of the Kutzneria genus.

中文翻译：

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来自 Kutzneria sp. 的新 30 成员大环内酯类 Epemicins A 和 B 的发现和表征。CA-103260

几十年来，放线菌一直是结构复杂的新型天然产物的丰富来源。虽然最大的属是链霉菌属，目前和过去临床使用的大多数抗生素最初都是从中分离出来的，但其他不太常见的属也有可能产生大量新型次级代谢产物。一个例子是Kutzneria属，目前仅包含五个报道的物种。这些物种之一是Kutzneria albidaDSM 43870T，具有 46 个预测的生物合成基因簇，已知可生产大环内酯类抗生素阿库霉素。在这里，我们报告了两种新型 30 元糖基化大环内酯类药物 epemicins A 和 B 的分离和结构表征，它们在结构上与阿库昔霉素有关，来自一种罕见的库兹纳菌sp. 两种化合物中所有手性中心的绝对构型是基于广泛的 1D 和 2D NMR 研究以及基因簇的生物信息学分析提出的。通过异源表达和基因失活，我们证实了生物合成基因簇与新分子之间的联系。这些发现显示了稀有放线菌产生新的、结构多样的代谢物的潜力。此外，基因失活是首次发表的对库兹纳菌属代表进行基因操作的报告。