RT Journal Article
SR Electronic
T1 Metabolite sequestration enables rapid recovery from nutrient depletion
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 590943
DO 10.1101/590943
A1 Christopher Hartline
A1 Ahmad A. Mannan
A1 Fuzhong Zhang
A1 Diego A. Oyarzún
YR 2019
UL http://biorxiv.org/content/early/2019/03/27/590943.abstract
AB Microbes adapt their metabolism to take advantage of nutrients in their environment [1]. Upon changes in nutrient conditions, transcriptional programs adapt pathway expression to meet the cellular energy budget [2]. Since nutrient abundance may change frequently, rapid pathway recovery is just as important as fast activation. Yet little is known about the regulatory strategies that microbes employ to accelerate their recovery from nutrient depletion. Using the fatty acid catabolic pathway in Escherichia coli as a model system, we show that fast recovery can be achieved by rapid release of a transcriptional regulator from a metabolite-sequestered complex. With a combination of theory and experiment, we show that recovery dynamics depend critically on the rate of metabolite consumption and the duration of the exposure to nutrient. We constructed and compared strains with re-wired regulatory architectures, which highlight negative autoregulation as a superior control strategy over constitutive expression and positive autoregulation. Our results have wide-ranging implications for our understanding of metabolic homeostasis and the design of gene control circuits for synthetic biology and metabolic engineering.