Department of Biomolecular Chemistry Leibniz Institute for Natural Product Research and Infection Biology , HKI , Beutenbergstrasse 11a , 07745 Jena , Germany.
Department for Evolutionary Ecology, Institute of Organismic and Molecular Evolution , Johannes Gutenberg University , Johann-Joachim-Becher-Weg 13 , 55128 Mainz , Germany.
ACS Chem Biol. 2018 Sep 21;13(9):2414-2420. doi: 10.1021/acschembio.8b00600. Epub 2018 Sep 4.
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.
伊考沙肽是一种不寻常的双尾脂环肽抗生素，最初从真菌培养物中分离得到。然而，其生物合成和生态功能仍然是个谜。通过对害虫甲虫 Lagria villosa 的细菌内共生体（ Burkholderia gladioli）的基因组挖掘和代谢分析，我们揭示了伊考沙肽的细菌起源。生物合成基因座的功能分析显示，一种前所未有的非核糖体肽合酶（NRPS）通过不同模块中的两个起始缩合结构域将两种β-羟基酸纳入其中。这种不寻常的装配线可能会激发新的合成生物学方法，在来自不同生境的许多共生 Burkholderia 物种中广泛存在。生物测定表明，伊考沙肽对昆虫病原细菌具有活性，从而增加了保护甲虫后代的化学武器库。通过创建一个缺失突变体，我们发现伊考沙肽是一种群集抑制剂，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。
