Gluconeogenic precursor availability regulates flux through the glyoxylate shunt in Pseudomonas aeruginosa

The Journal of Biological Chemistry
Audrey CrousillesMartin Welch

Abstract

The glyoxylate shunt bypasses the oxidative decarboxylation steps of the tricarboxylic acid (TCA) cycle, thereby conserving carbon skeletons for gluconeogenesis and biomass production. In Escherichia coli, carbon flux is redirected through the first enzyme of the glyoxylate shunt, isocitrate lyase (ICL), following phosphorylation and inactivation of the TCA cycle enzyme, isocitrate dehydrogenase (ICD), by the kinase/phosphatase, AceK. In contrast, mycobacterial species lack AceK and employ a phosphorylation-insensitive isocitrate dehydrogenase (IDH), which is allosterically activated by the product of ICL activity, glyoxylate. However, Pseudomonas aeruginosa expresses IDH, ICD, ICL, and AceK, raising the question of how these enzymes are regulated to ensure proper flux distribution between the competing pathways. Here, we present the structure, kinetics, and regulation of ICL, IDH, and ICD from P. aeruginosa We found that flux partitioning is coordinated through reciprocal regulation of these enzymes, linking distribution of carbon flux to the availability of the key gluconeogenic precursors, oxaloacetate and pyruvate. Specifically, a greater abundance of these metabolites activated IDH and inhibited ICL, leading to increased T...Continue Reading

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Citations

Mar 1, 2019·The New Phytologist·Stuart Daniel Woodcock, Jacob George Malone
Jun 13, 2019·Microbial Biotechnology·Stephen K DolanMartin Welch
Apr 9, 2020·International Journal of Molecular Sciences·Alyssa C McVeyMartin Welch
May 21, 2020·Frontiers in Microbiology·Morgan A AlfordRobert E W Hancock
Dec 12, 2020·Respiratory Research·Sebastián A Riquelme, Alice Prince

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