The PEP—pyruvate—oxaloacetate node as the switch point for carbon flux distribution in bacteria: We dedicate this paper to Rudolf K. Thauer, Director of the Max-Planck-Institute for Terrestrial Microbiology in Marburg, Germany, on the occasion of his 65th birthday

Abstract

In many organisms, metabolite interconversion at the phosphoenolpyruvate (PEP)-pyruvate-oxaloacetate node involves a structurally entangled set of reactions that interconnects the major pathways of carbon metabolism and thus, is responsible for the distribution of the carbon flux among catabolism, anabolism and energy supply of the cell. While sugar catabolism proceeds mainly via oxidative or non-oxidative decarboxylation of pyruvate to acetyl-CoA, anaplerosis and the initial steps of gluconeogenesis are accomplished by C3- (PEP- and/or pyruvate-) carboxylation and C4- (oxaloacetate- and/or malate-) decarboxylation, respectively. In contrast to the relatively uniform central metabolic pathways in bacteria, the set of enzymes at the PEP-pyruvate-oxaloacetate node represents a surprising diversity of reactions. Variable combinations are used in different bacteria and the question of the significance of all these reactions for growth and for biotechnological fermentation processes arises. This review summarizes what is known about the enzymes and the metabolic fluxes at the PEP-pyruvate-oxaloacetate node in bacteria, with a particular focus on the C3-carboxylation and C4-decarboxylation reactions in Escherichia coli, Bacillus subtilis and Corynebacterium glutamicum. We discuss the activities of the enzymes, their regulation and their specific contribution to growth under a given condition or to biotechnological metabolite production. The present knowledge unequivocally reveals the PEP-pyruvate-oxaloacetate nodes of bacteria to be a fascinating target of metabolic engineering in order to achieve optimized metabolite production.

Latent Pathway Activation and Increased Pathway Capacity Enable Escherichia coli Adaptation to Loss of Key Metabolic Enzymes

“…Generally, PEP carboxylase inactivation precludes growth on glucose as the sole carbon source, because this anaplerotic reaction replenishes tricarboxylic acid cycle intermediates that are withdrawn for biosynthesis (39). Physiological suppressor mutants occur rapidly, however, and the slow glucose growth phenotype of the unevolved, suppressed ppc mutant was almost fully recovered through adaptive evolution with indistinguishable physiology in the two evolved mutants (Table 1).…”

The Emergence of 2-Oxoglutarate as a Master Regulator Metabolite

“…E. coli can also replenish TCA cycle intermediates by using the glyoxylate shunt. However, the activity of the glyoxylate shunt is regulated by carbon catabolic repression (CCR) (28), and also by reversible phosphorylation of isocitrate dehydrogenase (29).…”

Long-Term Acclimation to Iron Limitation Reveals New Insights in Metabolism Regulation of Synechococcus sp. PCC7002

“…PCC7002 gradually modulates its metabolism according to the severity of Fe limitation. The ppsA encodes phosphoenolpyruvate synthase, a central enzyme of the gluconeogenesis pathway that synthetizes glucose from non-sugar compounds or the intermediates of the TCA cycle (Sauer and Eikmanns, 2005;Marrero et al, 2010). PpsA competes with pyruvate dehydrogenase, which mediates the formation of acetyl coenzyme A, the starting metabolite of the TCA cycle (Chao et al, 1993).…”