Icosalide is an unusual two-tailed lipocyclopeptide antibiotic that was originally isolated from a fungal culture. Yet, its biosynthesis and ecological function have remained enigmatic. By genome mining and metabolic profiling of a bacterial endosymbiont (Burkholderia gladioli) of the pest beetle Lagria villosa, we unveiled a bacterial origin of icosalide. Functional analysis of the biosynthetic gene locus revealed an unprecedented nonribosomal peptide synthetase (NRPS) that incorporates two β-hydroxy acids by means of two starter condensation domains in different modules. This unusual assembly line, which may inspire new synthetic biology approaches, is widespread among many symbiotic Burkholderia species from diverse habitats. Biological assays showed that icosalide is active against entomopathogenic bacteria, thus adding to the chemical armory protecting beetle offspring. By creating a null mutant, we found that icosalide is a swarming inhibitor, which may play a role in symbiotic interactions and bears the potential for therapeutic applications.

中文翻译：

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双尾缩肽大会五花八门：在抗生素Icosalide的意外细菌来源伯克霍尔德氏菌共生

二十碳四烯酸是一种不寻常的两尾脂环肽抗生素，最初是从真菌培养物中分离出来的。然而，它的生物合成和生态功能仍然是个谜。通过基因组挖掘和害虫甲虫Lagria villosa的细菌内共生体（Burkholderia gladioli）的代谢谱分析，我们揭示了二十碳内酰胺的细菌起源。生物合成基因基因座的功能分析表明，空前的非核糖体肽合成酶（NRPS）通过不同模块中的两个起始子缩合域掺入了两个β-羟基酸。这种不寻常的流水线可能会激发新的合成生物学方法，在许多共生的伯克霍尔德氏菌中广泛存在。来自不同栖息地的物种。生物测定表明，二十碳内酯对昆虫病原菌具有活性，因此增加了保护甲虫后代的化学武器库。通过创建无效突变体，我们发现二十碳内酯是一种成群的抑制剂，它可能在共生相互作用中发挥作用，并具有治疗应用的潜力。