Iorio Marianna, Gentile Andrea, Brunati Cristina, Tocchetti Arianna, Landini Paolo, Maffioli Sonia Ilaria, Donadio Stefano, Sosio Margherita
NAICONS Srl Milan Italy
Ktedogen Srl Milan Italy.
RSC Adv. 2022 Jun 6;12(26):16640-16655. doi: 10.1039/d2ra02094g. eCollection 2022 Jun 1.
In the search for structurally novel metabolites with antibacterial activity, innovative approaches must be implemented to increase the probability of discovering novel chemistry from microbial sources. Here we report on the application of metabolomic tools to the genus , a poorly explored member of the Actinobacteria. From examining extracts derived from 88 isolates belonging to this genus, we identified a family of cyclodepsipeptides acylated with a C polyketide chain, which we named allopeptimicins. These molecules possess unusual structural features, including several double bonds in the amino-polyketide chain and four non-proteinogenic amino acids in the octapeptide. Remarkably, allopeptimicins are produced as a complex of active and inactive congeners, the latter carrying a sulfate group on the polyketide amine. This modification is also a mechanism of self-protection in the producer strain. The structural uniqueness of allopeptimicins is reflected in a biosynthetic gene cluster showing a mosaic structure, with dedicated gene cassettes devoted to formation of specialized precursors and modular assembly lines related to those from different pathways.
在寻找具有抗菌活性的结构新颖的代谢产物时，必须采用创新方法来提高从微生物来源发现新化学物质的概率。在此，我们报告了代谢组学工具在放线菌属中一个研究较少的成员——[具体属名缺失]上的应用。通过检查来自该属88个分离株的提取物，我们鉴定出了一类由C聚酮链酰化的环缩肽，我们将其命名为别肽霉素。这些分子具有不寻常的结构特征，包括氨基聚酮链中的几个双键以及八肽中的四个非蛋白质氨基酸。值得注意的是，别肽霉素是以活性和非活性同系物的复合物形式产生的，后者在聚酮胺上带有一个硫酸基团。这种修饰也是产生菌株中的一种自我保护机制。别肽霉素的结构独特性体现在一个显示出镶嵌结构的生物合成基因簇中，其中有专门用于形成特殊前体的基因盒以及与来自不同途径的那些相关的模块化装配线。
