Ultrasensitive regulation of anapleurosis via allosteric activation of PEP carboxylase

Yi Fan Xu, Daniel Amador-Noguez, Marshall Louis Reaves, Xiao Jiang Feng, Joshua D. Rabinowitz

Research output: Contribution to journalArticle

55 Scopus citations

Abstract

Anapleurosis is the filling of the tricarboxylic acid cycle with four-carbon units. The common substrate for both anapleurosis and glucose phosphorylation in bacteria is the terminal glycolytic metabolite phosphoenolpyruvate (PEP). Here we show that Escherichia coli quickly and almost completely turns off PEP consumption upon glucose removal. The resulting buildup of PEP is used to quickly import glucose if it becomes available again. The switch-like termination of anapleurosis results from depletion of fructose-1,6-bisphosphate (FBP), an ultrasensitive allosteric activator of PEP carboxylase. E. coli expressing an FBP-insensitive point mutant of PEP carboxylase grow normally when glucose is steadily available. However, they fail to build up PEP upon glucose removal, grow poorly when glucose availability oscillates and suffer from futile cycling at the PEP node on gluconeogenic substrates. Thus, bacterial central carbon metabolism is intrinsically programmed with ultrasensitive allosteric regulation to enable rapid adaptation to changing environmental conditions.

Original languageEnglish (US)
Pages (from-to)562-568
Number of pages7
JournalNature Chemical Biology
Volume8
Issue number6
DOIs
StatePublished - Jun 2012

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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