CpxR和LrhA协调嗜线虫Xenorhabdus nematophila中Xenocoumacin 1生物合成、鞭毛组装和趋化性的调节
{"_":"CpxR and LrhA coordinate the regulation of Xenocoumacin 1 biosynthesis, flagellar assembly, and chemotaxis in .","i":["Xenorhabdus nematophila"]}
摘要(中文译文)
产生丰富的 specialized metabolites，具有重要的农业和医学应用前景，其中Xenocoumacin 1（Xcn1）是一种关键的抗真菌次级代谢产物。然而，调控Xcn1生物合成的转录调控机制仍未完全阐明，尤其是双组分系统反应调节因子CpxR与LysR型转录调控因子LrhA之间的直接调控联系尚不清楚。本研究结合蛋白质-DNA结合实验、突变体构建和转录组分析，解析了CpxR和LrhA在YL001中的协同调控作用。重组LrhA和CpxR经异源表达并纯化；电泳迁移率变动实验表明，LrhA直接结合、和的启动子，而CpxR靶向、和的启动子。值得注意的是，His标签修饰的位置对LrhA的DNA结合活性具有关键影响——C端标签消除了结合能力，而N端标签则保留了该能力。通过同源重组构建了缺失突变体，RNA测序结合生物信息学分析揭示，LrhA和CpxR对重叠的核心通路发挥相反的调控作用：LrhA正向调控鞭毛组装和细菌趋化性，而CpxR负向调控这些过程。GO和KEGG富集分析进一步揭示了这两个调控因子在碳水化合物转运和氨基酸代谢中的不同调控作用。综上所述，本研究证实CpxR直接激活转录，而LrhA直接抑制表达，形成精细调控Xcn1生物合成的调控级联。本研究阐明了CpxR和LrhA介导的复杂转录调控网络，为利用该细菌及其生物活性代谢产物进行生物技术应用提供了理论基础。
Abstract
produces a wealth of specialized metabolites with promising agricultural and medical applications, among which Xenocoumacin 1 (Xcn1) is a key antifungal secondary metabolite. The transcriptional regulatory mechanisms governing Xcn1 biosynthesis, however, remain incompletely characterized, particularly the direct regulatory links between the two-component system response regulator CpxR and the LysR-type transcriptional regulator LrhA. Here, we combined protein-DNA binding assays, mutant construction, and transcriptomic analysis to dissect the coordinated regulatory roles of CpxR and LrhA in YL001. Recombinant LrhA and CpxR were heterologously expressed and purified; electrophoretic mobility shift assays demonstrated that LrhA directly binds to the promoters of , , , and , whereas CpxR targets the promoters of , , and Notably, the position of His-tag modification critically impacts LrhA's DNA-binding activity-C-terminal tagging abrogated binding capacity, while N-terminal tagging preserved it. Deletion mutants were constructed via homologous recombination, and RNA sequencing coupled with bioinformatics analysis revealed that LrhA and CpxR exert opposing regulatory effects on overlapping core pathways: LrhA positively regulates flagellar assembly and bacterial chemotaxis, whereas CpxR negatively modulates these processes. GO and KEGG enrichment analyses further uncovered distinct regulatory roles of the two regulators in carbohydrate transport and amino acid metabolism. Collectively, our findings establish that CpxR directly activates transcription, and LrhA directly represses expression, forming a regulatory cascade that fine-tunes Xcn1 biosynthesis. This study elucidates the sophisticated transcriptional regulatory network mediated by CpxR and LrhA in , providing a theoretical basis for exploiting this bacterium and its bioactive metabolites for biotechnological applications.
如何引用
AMA
Yunfei Han, Haijiao Liu, Xintong Zhao, Mengru He, Yafei Chen, Tong Li, et al. {"_":"CpxR and LrhA coordinate the regulation of Xenocoumacin 1 biosynthesis, flagellar assembly, and chemotaxis in .","i":["Xenorhabdus nematophila"]}. Frontiers in microbiology. 2026; doi:10.3389/fmicb.2026.1831682.
APA
Yunfei Han, Haijiao Liu, Xintong Zhao, Mengru He, Yafei Chen, Tong Li, et al (2026). {"_":"CpxR and LrhA coordinate the regulation of Xenocoumacin 1 biosynthesis, flagellar assembly, and chemotaxis in .","i":["Xenorhabdus nematophila"]}. Frontiers in microbiology. https://doi.org/10.3389/fmicb.2026.1831682
GB/T 7714
Yunfei Han, Haijiao Liu, Xintong Zhao, Mengru He, Yafei Chen, Tong Li, et al. {"_":"CpxR and LrhA coordinate the regulation of Xenocoumacin 1 biosynthesis, flagellar assembly, and chemotaxis in .","i":["Xenorhabdus nematophila"]}[J]. Frontiers in microbiology, 2026 doi:10.3389/fmicb.2026.1831682.
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