Global Transcriptional Regulators Fine-Tune the Translational and Metabolic Efficiency for Optimal Growth of <named-content content-type="genus-species">Escherichia coli</named-content>

ABSTRACT Global transcriptional regulators coordinate complex genetic interactions that bestow better adaptability for an organism against external and internal perturbations. These transcriptional regulators are known to control an enormous array of genes with diverse functionalities. However, regu...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Mahesh S. Iyer, Ankita Pal, Sumana Srinivasan, Pramod R. Somvanshi, K. V. Venkatesh
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2021
Materias:	global transcriptional regulators metabolic and translational efficiency exponential growth intracellular metabolites proteome allocation anaerobic fermentation Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/f6a71fe7904a4a87a3b5f359b1868d28
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:f6a71fe7904a4a87a3b5f359b1868d28
record_format	dspace
spelling	oai:doaj.org-article:f6a71fe7904a4a87a3b5f359b1868d282021-12-02T18:21:19ZGlobal Transcriptional Regulators Fine-Tune the Translational and Metabolic Efficiency for Optimal Growth of <named-content content-type="genus-species">Escherichia coli</named-content>10.1128/mSystems.00001-212379-5077https://doaj.org/article/f6a71fe7904a4a87a3b5f359b1868d282021-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSystems.00001-21https://doaj.org/toc/2379-5077ABSTRACT Global transcriptional regulators coordinate complex genetic interactions that bestow better adaptability for an organism against external and internal perturbations. These transcriptional regulators are known to control an enormous array of genes with diverse functionalities. However, regulator-driven molecular mechanisms that underpin precisely tuned translational and metabolic processes conducive for rapid exponential growth remain obscure. Here, we comprehensively reveal the fundamental role of global transcriptional regulators FNR, ArcA, and IHF in sustaining translational and metabolic efficiency under glucose fermentative conditions in Escherichia coli. By integrating high-throughput gene expression profiles and absolute intracellular metabolite concentrations, we illustrate that these regulators are crucial in maintaining nitrogen homeostasis, govern expression of otherwise unnecessary or hedging genes, and exert tight control on metabolic bottleneck steps. Furthermore, we characterize changes in expression and activity profiles of other coregulators associated with these dysregulated metabolic pathways, determining the regulatory interactions within the transcriptional regulatory network. Such systematic findings emphasize their importance in optimizing the proteome allocation toward metabolic enzymes as well as ribosomes, facilitating condition-specific phenotypic outcomes. Consequentially, we reveal that disruption of this inherent trade-off between ribosome and metabolic proteome economy due to the loss of regulators resulted in lowered growth rates. Moreover, our findings reinforce that the accumulations of intracellular metabolites in the event of proteome repartitions negatively affects the glucose uptake. Overall, by extending the three-partition proteome allocation theory concordant with multi-omics measurements, we elucidate the physiological consequences of loss of global regulators on central carbon metabolism restraining the organism to attain maximal biomass synthesis. IMPORTANCE Cellular proteome allocation in response to environmental or internal perturbations governs their eventual phenotypic outcome. This entails striking an effective balance between amino acid biosynthesis by metabolic proteins and its consumption by ribosomes. However, the global transcriptional regulator-driven molecular mechanisms that underpin their coordination remains unexplored. Here, we emphasize that global transcriptional regulators, known to control expression of a myriad of genes, are fundamental for precisely tuning the translational and metabolic efficiencies that define the growth optimality. Towards this, we systematically characterized the single deletion effect of FNR, ArcA, and IHF regulators of Escherichia coli on exponential growth under anaerobic glucose fermentative conditions. Their absence disrupts the stringency of proteome allocation, which manifests as impairment in key metabolic processes and an accumulation of intracellular metabolites. Furthermore, by incorporating an extension to the empirical growth laws, we quantitatively demonstrate the general design principles underlying the existence of these regulators in E. coli.Mahesh S. IyerAnkita PalSumana SrinivasanPramod R. SomvanshiK. V. VenkateshAmerican Society for Microbiologyarticleglobal transcriptional regulatorsmetabolic and translational efficiencyexponential growthintracellular metabolitesproteome allocationanaerobic fermentationMicrobiologyQR1-502ENmSystems, Vol 6, Iss 2 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	global transcriptional regulators metabolic and translational efficiency exponential growth intracellular metabolites proteome allocation anaerobic fermentation Microbiology QR1-502
spellingShingle	global transcriptional regulators metabolic and translational efficiency exponential growth intracellular metabolites proteome allocation anaerobic fermentation Microbiology QR1-502 Mahesh S. Iyer Ankita Pal Sumana Srinivasan Pramod R. Somvanshi K. V. Venkatesh Global Transcriptional Regulators Fine-Tune the Translational and Metabolic Efficiency for Optimal Growth of <named-content content-type="genus-species">Escherichia coli</named-content>
description	ABSTRACT Global transcriptional regulators coordinate complex genetic interactions that bestow better adaptability for an organism against external and internal perturbations. These transcriptional regulators are known to control an enormous array of genes with diverse functionalities. However, regulator-driven molecular mechanisms that underpin precisely tuned translational and metabolic processes conducive for rapid exponential growth remain obscure. Here, we comprehensively reveal the fundamental role of global transcriptional regulators FNR, ArcA, and IHF in sustaining translational and metabolic efficiency under glucose fermentative conditions in Escherichia coli. By integrating high-throughput gene expression profiles and absolute intracellular metabolite concentrations, we illustrate that these regulators are crucial in maintaining nitrogen homeostasis, govern expression of otherwise unnecessary or hedging genes, and exert tight control on metabolic bottleneck steps. Furthermore, we characterize changes in expression and activity profiles of other coregulators associated with these dysregulated metabolic pathways, determining the regulatory interactions within the transcriptional regulatory network. Such systematic findings emphasize their importance in optimizing the proteome allocation toward metabolic enzymes as well as ribosomes, facilitating condition-specific phenotypic outcomes. Consequentially, we reveal that disruption of this inherent trade-off between ribosome and metabolic proteome economy due to the loss of regulators resulted in lowered growth rates. Moreover, our findings reinforce that the accumulations of intracellular metabolites in the event of proteome repartitions negatively affects the glucose uptake. Overall, by extending the three-partition proteome allocation theory concordant with multi-omics measurements, we elucidate the physiological consequences of loss of global regulators on central carbon metabolism restraining the organism to attain maximal biomass synthesis. IMPORTANCE Cellular proteome allocation in response to environmental or internal perturbations governs their eventual phenotypic outcome. This entails striking an effective balance between amino acid biosynthesis by metabolic proteins and its consumption by ribosomes. However, the global transcriptional regulator-driven molecular mechanisms that underpin their coordination remains unexplored. Here, we emphasize that global transcriptional regulators, known to control expression of a myriad of genes, are fundamental for precisely tuning the translational and metabolic efficiencies that define the growth optimality. Towards this, we systematically characterized the single deletion effect of FNR, ArcA, and IHF regulators of Escherichia coli on exponential growth under anaerobic glucose fermentative conditions. Their absence disrupts the stringency of proteome allocation, which manifests as impairment in key metabolic processes and an accumulation of intracellular metabolites. Furthermore, by incorporating an extension to the empirical growth laws, we quantitatively demonstrate the general design principles underlying the existence of these regulators in E. coli.
format	article
author	Mahesh S. Iyer Ankita Pal Sumana Srinivasan Pramod R. Somvanshi K. V. Venkatesh
author_facet	Mahesh S. Iyer Ankita Pal Sumana Srinivasan Pramod R. Somvanshi K. V. Venkatesh
author_sort	Mahesh S. Iyer
title	Global Transcriptional Regulators Fine-Tune the Translational and Metabolic Efficiency for Optimal Growth of <named-content content-type="genus-species">Escherichia coli</named-content>
title_short	Global Transcriptional Regulators Fine-Tune the Translational and Metabolic Efficiency for Optimal Growth of <named-content content-type="genus-species">Escherichia coli</named-content>
title_full	Global Transcriptional Regulators Fine-Tune the Translational and Metabolic Efficiency for Optimal Growth of <named-content content-type="genus-species">Escherichia coli</named-content>
title_fullStr	Global Transcriptional Regulators Fine-Tune the Translational and Metabolic Efficiency for Optimal Growth of <named-content content-type="genus-species">Escherichia coli</named-content>
title_full_unstemmed	Global Transcriptional Regulators Fine-Tune the Translational and Metabolic Efficiency for Optimal Growth of <named-content content-type="genus-species">Escherichia coli</named-content>
title_sort	global transcriptional regulators fine-tune the translational and metabolic efficiency for optimal growth of <named-content content-type="genus-species">escherichia coli</named-content>
publisher	American Society for Microbiology
publishDate	2021
url	https://doaj.org/article/f6a71fe7904a4a87a3b5f359b1868d28
work_keys_str_mv	AT maheshsiyer globaltranscriptionalregulatorsfinetunethetranslationalandmetabolicefficiencyforoptimalgrowthofnamedcontentcontenttypegenusspeciesescherichiacolinamedcontent AT ankitapal globaltranscriptionalregulatorsfinetunethetranslationalandmetabolicefficiencyforoptimalgrowthofnamedcontentcontenttypegenusspeciesescherichiacolinamedcontent AT sumanasrinivasan globaltranscriptionalregulatorsfinetunethetranslationalandmetabolicefficiencyforoptimalgrowthofnamedcontentcontenttypegenusspeciesescherichiacolinamedcontent AT pramodrsomvanshi globaltranscriptionalregulatorsfinetunethetranslationalandmetabolicefficiencyforoptimalgrowthofnamedcontentcontenttypegenusspeciesescherichiacolinamedcontent AT kvvenkatesh globaltranscriptionalregulatorsfinetunethetranslationalandmetabolicefficiencyforoptimalgrowthofnamedcontentcontenttypegenusspeciesescherichiacolinamedcontent
_version_	1718378192212852736

Global Transcriptional Regulators Fine-Tune the Translational and Metabolic Efficiency for Optimal Growth of <named-content content-type="genus-species">Escherichia coli</named-content>

Ejemplares similares