Metabolite Sequestration Enables Rapid Recovery from Fatty Acid Depletion in <named-content content-type="genus-species">Escherichia coli</named-content>

ABSTRACT Microbes adapt their metabolism to take advantage of nutrients in their environment. Such adaptations control specific metabolic pathways to match energetic demands with nutrient availability. Upon depletion of nutrients, rapid pathway recovery is key to release cellular resources required...

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Autores principales:	Christopher J. Hartline, Ahmad A. Mannan, Di Liu, Fuzhong Zhang, Diego A. Oyarzún
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	metabolic dynamics metabolic regulation synthetic biology transcription factor Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/da29ed6c5fcd4335ad30b64e6be69db5
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spelling	oai:doaj.org-article:da29ed6c5fcd4335ad30b64e6be69db52021-11-15T15:57:02ZMetabolite Sequestration Enables Rapid Recovery from Fatty Acid Depletion in <named-content content-type="genus-species">Escherichia coli</named-content>10.1128/mBio.03112-192150-7511https://doaj.org/article/da29ed6c5fcd4335ad30b64e6be69db52020-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.03112-19https://doaj.org/toc/2150-7511ABSTRACT Microbes adapt their metabolism to take advantage of nutrients in their environment. Such adaptations control specific metabolic pathways to match energetic demands with nutrient availability. Upon depletion of nutrients, rapid pathway recovery is key to release cellular resources required for survival under the new nutritional conditions. Yet, little is known about the regulatory strategies that microbes employ to accelerate pathway recovery in response to nutrient depletion. Using the fatty acid catabolic pathway in Escherichia coli, here, we show that fast recovery can be achieved by rapid release of a transcriptional regulator from a metabolite-sequestered complex. With a combination of mathematical modeling and experiments, we show that recovery dynamics depend critically on the rate of metabolite consumption and the exposure time to nutrients. We constructed strains with rewired transcriptional regulatory architectures that highlight the metabolic benefits of negative autoregulation over constitutive and positive autoregulation. Our results have wide-ranging implications for our understanding of metabolic adaptations, as well as for guiding the design of gene circuitry for synthetic biology and metabolic engineering. IMPORTANCE Rapid metabolic recovery during nutrient shift is critical to microbial survival, cell fitness, and competition among microbiota, yet little is known about the regulatory mechanisms of rapid metabolic recovery. This work demonstrates a previously unknown mechanism where rapid release of a transcriptional regulator from a metabolite-sequestered complex enables fast recovery to nutrient depletion. The work identified key regulatory architectures and parameters that control the speed of recovery, with wide-ranging implications for the understanding of metabolic adaptations as well as synthetic biology and metabolic engineering.Christopher J. HartlineAhmad A. MannanDi LiuFuzhong ZhangDiego A. OyarzúnAmerican Society for Microbiologyarticlemetabolic dynamicsmetabolic regulationsynthetic biologytranscription factorMicrobiologyQR1-502ENmBio, Vol 11, Iss 2 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	metabolic dynamics metabolic regulation synthetic biology transcription factor Microbiology QR1-502
spellingShingle	metabolic dynamics metabolic regulation synthetic biology transcription factor Microbiology QR1-502 Christopher J. Hartline Ahmad A. Mannan Di Liu Fuzhong Zhang Diego A. Oyarzún Metabolite Sequestration Enables Rapid Recovery from Fatty Acid Depletion in <named-content content-type="genus-species">Escherichia coli</named-content>
description	ABSTRACT Microbes adapt their metabolism to take advantage of nutrients in their environment. Such adaptations control specific metabolic pathways to match energetic demands with nutrient availability. Upon depletion of nutrients, rapid pathway recovery is key to release cellular resources required for survival under the new nutritional conditions. Yet, little is known about the regulatory strategies that microbes employ to accelerate pathway recovery in response to nutrient depletion. Using the fatty acid catabolic pathway in Escherichia coli, here, we show that fast recovery can be achieved by rapid release of a transcriptional regulator from a metabolite-sequestered complex. With a combination of mathematical modeling and experiments, we show that recovery dynamics depend critically on the rate of metabolite consumption and the exposure time to nutrients. We constructed strains with rewired transcriptional regulatory architectures that highlight the metabolic benefits of negative autoregulation over constitutive and positive autoregulation. Our results have wide-ranging implications for our understanding of metabolic adaptations, as well as for guiding the design of gene circuitry for synthetic biology and metabolic engineering. IMPORTANCE Rapid metabolic recovery during nutrient shift is critical to microbial survival, cell fitness, and competition among microbiota, yet little is known about the regulatory mechanisms of rapid metabolic recovery. This work demonstrates a previously unknown mechanism where rapid release of a transcriptional regulator from a metabolite-sequestered complex enables fast recovery to nutrient depletion. The work identified key regulatory architectures and parameters that control the speed of recovery, with wide-ranging implications for the understanding of metabolic adaptations as well as synthetic biology and metabolic engineering.
format	article
author	Christopher J. Hartline Ahmad A. Mannan Di Liu Fuzhong Zhang Diego A. Oyarzún
author_facet	Christopher J. Hartline Ahmad A. Mannan Di Liu Fuzhong Zhang Diego A. Oyarzún
author_sort	Christopher J. Hartline
title	Metabolite Sequestration Enables Rapid Recovery from Fatty Acid Depletion in <named-content content-type="genus-species">Escherichia coli</named-content>
title_short	Metabolite Sequestration Enables Rapid Recovery from Fatty Acid Depletion in <named-content content-type="genus-species">Escherichia coli</named-content>
title_full	Metabolite Sequestration Enables Rapid Recovery from Fatty Acid Depletion in <named-content content-type="genus-species">Escherichia coli</named-content>
title_fullStr	Metabolite Sequestration Enables Rapid Recovery from Fatty Acid Depletion in <named-content content-type="genus-species">Escherichia coli</named-content>
title_full_unstemmed	Metabolite Sequestration Enables Rapid Recovery from Fatty Acid Depletion in <named-content content-type="genus-species">Escherichia coli</named-content>
title_sort	metabolite sequestration enables rapid recovery from fatty acid depletion in <named-content content-type="genus-species">escherichia coli</named-content>
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/da29ed6c5fcd4335ad30b64e6be69db5
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Metabolite Sequestration Enables Rapid Recovery from Fatty Acid Depletion in <named-content content-type="genus-species">Escherichia coli</named-content>

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