Posttranslational Control of PlsB Is Sufficient To Coordinate Membrane Synthesis with Growth in <named-content content-type="genus-species">Escherichia coli</named-content>

ABSTRACT Every cell must produce enough membrane to contain itself. However, the mechanisms by which the rate of membrane synthesis is coupled with the rate of cell growth remain unresolved. By comparing substrate and enzyme concentrations of the fatty acid and phospholipid synthesis pathways of Esc...

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Autores principales:	Marek J. Noga, Ferhat Büke, Niels J. F. van den Broek, Nicole C. E. Imholz, Nicole Scherer, Flora Yang, Gregory Bokinsky
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	fatty acids lipopolysaccharide membrane biogenesis metabolic regulation phospholipids posttranslational regulation Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/1a339936fa9549dbb9bf53ce45f0fd53
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spelling	oai:doaj.org-article:1a339936fa9549dbb9bf53ce45f0fd532021-11-15T15:56:43ZPosttranslational Control of PlsB Is Sufficient To Coordinate Membrane Synthesis with Growth in <named-content content-type="genus-species">Escherichia coli</named-content>10.1128/mBio.02703-192150-7511https://doaj.org/article/1a339936fa9549dbb9bf53ce45f0fd532020-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02703-19https://doaj.org/toc/2150-7511ABSTRACT Every cell must produce enough membrane to contain itself. However, the mechanisms by which the rate of membrane synthesis is coupled with the rate of cell growth remain unresolved. By comparing substrate and enzyme concentrations of the fatty acid and phospholipid synthesis pathways of Escherichia coli across a 3-fold range of carbon-limited growth rates, we show that the rate of membrane phospholipid synthesis during steady-state growth is determined principally through allosteric control of a single enzyme, PlsB. Due to feedback regulation of the fatty acid pathway, PlsB activity also indirectly controls synthesis of lipopolysaccharide, a major component of the outer membrane synthesized from a fatty acid synthesis intermediate. Surprisingly, concentrations of the enzyme that catalyzes the committed step of lipopolysaccharide synthesis (LpxC) do not differ across steady-state growth conditions, suggesting that steady-state lipopolysaccharide synthesis is modulated primarily via indirect control by PlsB. In contrast to steady-state regulation, we found that responses to environmental perturbations are triggered directly via changes in acetyl coenzyme A (acetyl-CoA) concentrations, which enable rapid adaptation. Adaptations are further modulated by ppGpp, which regulates PlsB activity during slow growth and growth arrest. The strong reliance of the membrane synthesis pathway upon posttranslational regulation ensures both the reliability and the responsiveness of membrane synthesis. IMPORTANCE How do bacterial cells grow without breaking their membranes? Although the biochemistry of fatty acid and membrane synthesis is well known, how membrane synthesis is balanced with growth and metabolism has remained unclear. This is partly due to the many control points that have been discovered within the membrane synthesis pathways. By precisely establishing the contributions of individual pathway enzymes, our results simplify the model of membrane biogenesis in the model bacterial species Escherichia coli. Specifically, we found that allosteric control of a single enzyme, PlsB, is sufficient to balance growth with membrane synthesis and to ensure that growing E. coli cells produce sufficient membrane. Identifying the signals that activate and deactivate PlsB will resolve the issue of how membrane synthesis is synchronized with growth.Marek J. NogaFerhat BükeNiels J. F. van den BroekNicole C. E. ImholzNicole SchererFlora YangGregory BokinskyAmerican Society for Microbiologyarticlefatty acidslipopolysaccharidemembrane biogenesismetabolic regulationphospholipidsposttranslational regulationMicrobiologyQR1-502ENmBio, Vol 11, Iss 4 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	fatty acids lipopolysaccharide membrane biogenesis metabolic regulation phospholipids posttranslational regulation Microbiology QR1-502
spellingShingle	fatty acids lipopolysaccharide membrane biogenesis metabolic regulation phospholipids posttranslational regulation Microbiology QR1-502 Marek J. Noga Ferhat Büke Niels J. F. van den Broek Nicole C. E. Imholz Nicole Scherer Flora Yang Gregory Bokinsky Posttranslational Control of PlsB Is Sufficient To Coordinate Membrane Synthesis with Growth in <named-content content-type="genus-species">Escherichia coli</named-content>
description	ABSTRACT Every cell must produce enough membrane to contain itself. However, the mechanisms by which the rate of membrane synthesis is coupled with the rate of cell growth remain unresolved. By comparing substrate and enzyme concentrations of the fatty acid and phospholipid synthesis pathways of Escherichia coli across a 3-fold range of carbon-limited growth rates, we show that the rate of membrane phospholipid synthesis during steady-state growth is determined principally through allosteric control of a single enzyme, PlsB. Due to feedback regulation of the fatty acid pathway, PlsB activity also indirectly controls synthesis of lipopolysaccharide, a major component of the outer membrane synthesized from a fatty acid synthesis intermediate. Surprisingly, concentrations of the enzyme that catalyzes the committed step of lipopolysaccharide synthesis (LpxC) do not differ across steady-state growth conditions, suggesting that steady-state lipopolysaccharide synthesis is modulated primarily via indirect control by PlsB. In contrast to steady-state regulation, we found that responses to environmental perturbations are triggered directly via changes in acetyl coenzyme A (acetyl-CoA) concentrations, which enable rapid adaptation. Adaptations are further modulated by ppGpp, which regulates PlsB activity during slow growth and growth arrest. The strong reliance of the membrane synthesis pathway upon posttranslational regulation ensures both the reliability and the responsiveness of membrane synthesis. IMPORTANCE How do bacterial cells grow without breaking their membranes? Although the biochemistry of fatty acid and membrane synthesis is well known, how membrane synthesis is balanced with growth and metabolism has remained unclear. This is partly due to the many control points that have been discovered within the membrane synthesis pathways. By precisely establishing the contributions of individual pathway enzymes, our results simplify the model of membrane biogenesis in the model bacterial species Escherichia coli. Specifically, we found that allosteric control of a single enzyme, PlsB, is sufficient to balance growth with membrane synthesis and to ensure that growing E. coli cells produce sufficient membrane. Identifying the signals that activate and deactivate PlsB will resolve the issue of how membrane synthesis is synchronized with growth.
format	article
author	Marek J. Noga Ferhat Büke Niels J. F. van den Broek Nicole C. E. Imholz Nicole Scherer Flora Yang Gregory Bokinsky
author_facet	Marek J. Noga Ferhat Büke Niels J. F. van den Broek Nicole C. E. Imholz Nicole Scherer Flora Yang Gregory Bokinsky
author_sort	Marek J. Noga
title	Posttranslational Control of PlsB Is Sufficient To Coordinate Membrane Synthesis with Growth in <named-content content-type="genus-species">Escherichia coli</named-content>
title_short	Posttranslational Control of PlsB Is Sufficient To Coordinate Membrane Synthesis with Growth in <named-content content-type="genus-species">Escherichia coli</named-content>
title_full	Posttranslational Control of PlsB Is Sufficient To Coordinate Membrane Synthesis with Growth in <named-content content-type="genus-species">Escherichia coli</named-content>
title_fullStr	Posttranslational Control of PlsB Is Sufficient To Coordinate Membrane Synthesis with Growth in <named-content content-type="genus-species">Escherichia coli</named-content>
title_full_unstemmed	Posttranslational Control of PlsB Is Sufficient To Coordinate Membrane Synthesis with Growth in <named-content content-type="genus-species">Escherichia coli</named-content>
title_sort	posttranslational control of plsb is sufficient to coordinate membrane synthesis with growth in <named-content content-type="genus-species">escherichia coli</named-content>
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/1a339936fa9549dbb9bf53ce45f0fd53
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Posttranslational Control of PlsB Is Sufficient To Coordinate Membrane Synthesis with Growth in <named-content content-type="genus-species">Escherichia coli</named-content>

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