Xenorhabdus and Photorhabdus species dedicate a large amount of resources to the production of specialized metabolites derived from non-ribosomal peptide synthetase (NRPS) or polyketide synthase (PKS). Both bacteria undergo symbiosis with nematodes, which is followed by an insect pathogenic phase. So far, the molecular basis of this tripartite relationship and the exact roles that individual metabolites and metabolic pathways play have not been well understood. To close this gap, we have significantly expanded the database for comparative genomics studies in these bacteria. Clustering the genes encoded in the individual genomes into hierarchical orthologous groups reveals a high-resolution picture of functional evolution in this clade. It identifies groups of genes-many of which are involved in secondary metabolite production-that may account for the niche specificity of these bacteria. Photorhabdus and Xenorhabdus appear very similar at the DNA sequence level, which indicates their close evolutionary relationship. Yet, high-resolution mass spectrometry analyses reveal a huge chemical diversity in the two taxa. Molecular network reconstruction identified a large number of previously unidentified metabolite classes, including the xefoampeptides and tilivalline. Here, we apply genomic and metabolomic methods in a complementary manner to identify and elucidate additional classes of natural products. We also highlight the ability to rapidly and simultaneously identify potentially interesting bioactive products from NRPSs and PKSs, thereby augmenting the contribution of molecular biology techniques to the acceleration of natural product discovery.

中文翻译：

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与线虫共生的Photorhabdus和Xenorhabdus相关的天然产物多样性。

Xenorhabdus和Photorhabdus物种将大量资源用于生产衍生自非核糖体肽合成酶（NRPS）或聚酮化合物合酶（PKS）的专门代谢产物。两种细菌都与线虫共生，随后是昆虫致病期。到目前为止，这种三重关系的分子基础以及单个代谢物和代谢途径所起的确切作用尚未得到很好的了解。为了缩小这一差距，我们已大大扩展了数据库，用于这些细菌的比较基因组学研究。将单个基因组中编码的基因聚类为分层直系同源群体，揭示了该进化枝中功能进化的高分辨率图片。它鉴定了可能与这些细菌的利基特异性有关的基因组，其中许多与次级代谢产物的产生有关。Photorhabdus和Xenorhabdus在DNA序列水平上看起来非常相似，这表明它们有着密切的进化关系。然而，高分辨率质谱分析显示这两个类群具有巨大的化学多样性。分子网络重建确定了许多先前未鉴定的代谢物类别，包括异戊二烯肽和蒂佛利林。在这里，我们以互补的方式应用基因组学和代谢组学方法来识别和阐明天然产物的其他类别。我们还强调了快速并同时从NRPS和PKS中识别出潜在有趣的生物活性产品的能力，