Metabolite sequestration enables rapid recovery from fatty acid depletion in Escherichia coli

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 survi...

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Bibliographic Details
Published inbioRxiv
Main Authors Hartline, Christopher J, Mannan, Ahmad A, Liu, Di, Zhang, Fuzhong, Oyarzún, Diego A
Format Paper
LanguageEnglish
Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 02.02.2020
Subjects
Adaptation
Escherichia coli
Mathematical models
Metabolic engineering
Metabolic pathways
Metabolism
Metabolites
Nutrient availability
Nutrients
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Summary: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 in the new nutritional condition. 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 modelling and experiments, we show that recovery dynamics depend critically on the rate of metabolite consumption and the exposure time to nutrient. We constructed strains with re-wired 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 guiding the design of gene circuitry for synthetic biology and metabolic engineering.
DOI:10.1101/590943