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代谢组学揭示环磷酸腺苷受体蛋白调节[具体物种]中的氮和肽聚糖合成。

Metabolomics reveals that the cAMP receptor protein regulates nitrogen and peptidoglycan synthesis in .

作者信息

Liu Yi, Rebollo-Ramirez Sonia, Larrouy-Maumus Gerald

机构信息

MRC Centre for Molecular Bacteriology and Infection, Department of Life Sciences, Faculty of Natural Sciences, Imperial College London, London, UK. Email:

出版信息

RSC Adv. 2020 Jul 14;10(44):26212-26219. doi: 10.1039/d0ra05153e. Epub 2020 Jul 10.

Abstract

requires extensive sensing and response to environment for its successful survival and pathogenesis, and signalling by cyclic adenosine 3',5'-monophosphate (cAMP) is an important mechanism. cAMP regulates expression of target genes interaction with downstream proteins, one of which is cAMP receptor protein (CRP), a global transcriptional regulator. Previous genomic works had identified regulon of CRP and investigated transcriptional changes in deletion mutant, however a link to downstream metabolomic events were lacking, which would help better understand roles of CRP. This work aims at investigating changes at metabolome level in deletion mutant combining untargeted LC-MS analysis and C isotope tracing analysis. The results were compared with previously published RNA sequencing data. We identified increasing abundances of metabolites related to nitrogen metabolism including ornithine, citrulline and glutamate derivatives, while C isotope labelling analysis further showed changes in turnover of these metabolites and amino acids, suggesting regulatory roles of CRP in nitrogen metabolism. Upregulation of diaminopimelic acid and its related genes also suggested role of CRP in regulation of peptidoglycan synthesis. This study provides insights on metabolomic aspects of cAMP-CRP regulatory pathway in and links to previously published transcriptomic data drawing a more complete map.

摘要

为了成功存活和致病,它需要对环境进行广泛的感知和响应,而环磷酸腺苷(cAMP)信号传导是一种重要机制。cAMP调节靶基因的表达以及与下游蛋白质的相互作用,其中之一是cAMP受体蛋白(CRP),一种全局转录调节因子。先前的基因组研究已经确定了CRP的调控子,并研究了缺失突变体中的转录变化,然而缺乏与下游代谢组学事件的联系,而这将有助于更好地理解CRP的作用。这项工作旨在结合非靶向液相色谱-质谱分析和碳同位素示踪分析,研究缺失突变体在代谢组水平上的变化。将结果与先前发表的RNA测序数据进行比较。我们发现与氮代谢相关的代谢物丰度增加,包括鸟氨酸、瓜氨酸和谷氨酸衍生物,而碳同位素标记分析进一步显示了这些代谢物和氨基酸周转的变化,表明CRP在氮代谢中具有调节作用。二氨基庚二酸及其相关基因的上调也表明CRP在肽聚糖合成调节中的作用。本研究提供了关于cAMP-CRP调控途径在代谢组学方面的见解,并与先前发表的转录组数据建立联系,绘制了更完整的图谱。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c9e/9055309/5c4080dcb7d6/d0ra05153e-f1.jpg

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