Metabolic Regulation and Coordination of the Metabolism in Bacteria in Response to a Variety of Growth Conditions

Shimizu, Kazuyuki

doi:10.1007/10_2015_320

Cited by 34 publications

(34 citation statements)

References 297 publications

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“…are exposed to a complex and dynamic physical and chemical environment, and must constantly adapt their cell physiology by changing the expression patterns of membrane proteins, secreted small molecules, and enzymes [1]. This ability to gauge the surroundings and modulate gene expression accordingly is crucial for effective environmental adaptation [2].…”

Section: Introductionmentioning

confidence: 99%

One ligand, two regulators and three binding sites: How KDPG controls primary carbon metabolism in Pseudomonas

et al. 2017

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Effective regulation of primary carbon metabolism is critically important for bacteria to successfully adapt to different environments. We have identified an uncharacterised transcriptional regulator; RccR, that controls this process in response to carbon source availability. Disruption of rccR in the plant-associated microbe Pseudomonas fluorescens inhibits growth in defined media, and compromises its ability to colonise the wheat rhizosphere. Structurally, RccR is almost identical to the Entner-Doudoroff (ED) pathway regulator HexR, and both proteins are controlled by the same ED-intermediate; 2-keto-3-deoxy-6-phosphogluconate (KDPG). Despite these similarities, HexR and RccR control entirely different aspects of primary metabolism, with RccR regulating pyruvate metabolism (aceEF), the glyoxylate shunt (aceA, glcB, pntAA) and gluconeogenesis (pckA, gap). RccR displays complex and unusual regulatory behaviour; switching repression between the pyruvate metabolism and glyoxylate shunt/gluconeogenesis loci depending on the available carbon source. This regulatory complexity is enabled by two distinct pseudo-palindromic binding sites, differing only in the length of their linker regions, with KDPG binding increasing affinity for the 28 bp aceA binding site but decreasing affinity for the 15 bp aceE site. Thus, RccR is able to simultaneously suppress and activate gene expression in response to carbon source availability. Together, the RccR and HexR regulators enable the rapid coordination of multiple aspects of primary carbon metabolism, in response to levels of a single key intermediate.

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Section: Introductionmentioning

confidence: 99%

One ligand, two regulators and three binding sites: How KDPG controls primary carbon metabolism in Pseudomonas

et al. 2017

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“…Overexpression of the gene, if it is not appropriately phosphorylated, might not be enough to reveal a phenotype. GlnK is a PII family signal transducer protein that modulates the activity of multiple biosynthetic and regulatory proteins in nitrogen metabolism (Arcondéguy et al, 2001;Gerhardt et al, 2015;Shimizu, 2016). It would make sense that nitrogen levels would exert an effect on bottromycin biosynthesis, due to the peptidic nature of bottromycin and in fact a paralog of this protein has been shown to affect secondary metabolite production in S. coelicolor (Waldvogel et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Regulation of Bottromycin Biosynthesis Involves an Internal Transcriptional Start Site and a Cluster-Situated Modulator

et al. 2020

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Bottromycin is a ribosomally synthesized and post-translationally modified peptide (RiPP) produced by several streptomycetes, including the plant pathogen Streptomyces scabies. There is significant interest in this molecule as it possesses strong antibacterial activity against clinically relevant multidrug resistant pathogens and is structurally distinct from all other antibiotics. However, studies into its efficacy are hampered by poor yields. An understanding of how bottromycin biosynthesis is regulated could aid the development of strategies to increase titres. Here, we use 5-tag-RNA-seq to identify the transcriptional organization of the gene cluster, which includes an internal transcriptional start site that precedes btmD, the gene that encodes the bottromycin precursor peptide. We show that the gene cluster does not encode a master regulator that controls pathway expression and instead encodes a regulatory gene, btmL, which functions as a modulator that specifically affects the expression of btmD but not genes up-or downstream of btmD. In order to identify non-cluster associated proteins involved in regulation, proteins were identified that bind to the main promoter of the pathway, which precedes btmC. This study provides insights into how this deceptively complex pathway is regulated in the absence of a pathway specific master regulator, and how it might coordinate with the central metabolism of the cell.

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“…Analogous to the known stress/starvation sigma σ S -controlled csiD-ygaF-gabDTP region (15,19), the yne operon is dependent on the environmental sigma factor σ E . Growth of the ptrR mutant with Glu as the sole nitrogen source and glycerol as the carbon source allows production of ppGpp (33,34).…”

Section: Discussionmentioning

confidence: 99%

PtrR (YneJ) is a novel E. coli transcription factor regulating the putrescine stress response and glutamate utilization

Rodionova

Gao

Sastry³

et al. 2020

Preprint

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Although polyamines, such as putrescine (Ptr), induce envelope stress for bacteria, they are important as nitrogen and carbon sources. Ptr utilization in Escherichia coli involves protein glutamylation, and glutamate stands at a crossroads between catabolism and anabolism. This communication reports that the transcription factor YneJ, here renamed PtrR, is involved in the regulation of a small regulatory RNA gene, fnrS, and an operon, yneIHGF, encoding succinatesemialdehyde dehydrogenase, Sad (YneI), glutaminase, GlsB (YneH), and several other genes.The yneI promoter is activated during putrescine utilization under nitrogen/carbon starvation conditions, and we show that PtrR is important for the putrescine stress response. It is also a repressor of fnrS gene expression, involved in the cascade regulation of mRNA synthesis for the marA and sodB genes, involved in antibiotic responses. PtrR transcriptional regulation of fnrS leads to a regulatory cascade induced by this small RNA that affects mRNA levels of ompF and the multidrug resistance regulator, MarA. We propose that PtrR functions as a dual activator/repressor, and that its regulation is important for the responses to different stress conditions involving L-glutamine/L-glutamate and putrescine utilization.

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Metabolic Regulation and Coordination of the Metabolism in Bacteria in Response to a Variety of Growth Conditions

Cited by 34 publications

References 297 publications

One ligand, two regulators and three binding sites: How KDPG controls primary carbon metabolism in Pseudomonas

One ligand, two regulators and three binding sites: How KDPG controls primary carbon metabolism in Pseudomonas

Regulation of Bottromycin Biosynthesis Involves an Internal Transcriptional Start Site and a Cluster-Situated Modulator

PtrR (YneJ) is a novel E. coli transcription factor regulating the putrescine stress response and glutamate utilization

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