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Elsevier BV Journal of Biological Chemistry 301(5)
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    초록·키워드

    Sensing and responding to O2 is an essential process for many bacteria, and O2 levels are linked to many pathways and phenotypes, such as metabolism, stress tolerance, motility, and virulence.One way through which the facultatively anaerobic bacterium Escherichia coli responds to environmental O2 is through the O2-sensing cyclic-di-GMP metabolic complex, DosCP.DosC synthesizes cyclic-di-GMP, while DosP breaks it down, and both proteins modulate their activity in response to changes in O2 levels.Cyclic-di-GMP is a bacterial second messenger that has been widely studied and shown to have roles in biofilm formation, motility, virulence, and stress tolerance.DosC has been linked to curli biofilm fiber production and the DosCP complex has been shown to interact in vitro with the ribonucleases RNase E and Polynucleotide Phosphorylase (PNPase), suggesting a role in RNA degradation.While much of the previous studies have focused on DosC, this works investigates the cellular roles of the DosC/ DosP complex and the effects on O2-dependent c-di-GMP metabolism.Using TurboID proximity labeling, transcriptomic analysis, phenotypic studies, metabolomics, and ligand-binding assays, this work aims to elucidate the role of the DosCP complex in E. coli physiology and the downstream c-di-GMP signaling pathway.Results demonstrate that the DosCP complex alters manganese and iron homeostasis, highlighting a role in response to metal stress.In addition, proximity labeling studies and growth assays on various carbon sources suggest that a number of proteins involved in central metabolism are potentially involved in DosCP downstream c-di-GMP signaling.Current studies are investigating the c-di-GMP binding ability of the identified enzymes.This work proposes a key new link between oxygen sensing, c-di-GMP signaling, and central metabolism.While the exact pathway of signal transduction remains under investigation, these results highlight the increasingly broad role of c-di-GMP in bacterial physiology.

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