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J. Biol. Chem., Vol. 278, Issue 47, 46446-46451, November 21, 2003

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A Novel Metabolic Cycle Catalyzes Glucose Oxidation and Anaplerosis in Hungry Escherichia coli^*

Eliane Fischer and Uwe Sauer

From the Institute of Biotechnology, ETH Zürich, CH-8093 Zürich, Switzerland

Complete oxidation of carbohydrates to CO₂ is considered to be the exclusive property of the ubiquitous tricarboxylic acid cycle, the central process in cellular energy metabolism of aerobic organisms. Based on metabolism-wide in vivo quantification of intracellular carbon fluxes, we describe here complete oxidation of carbohydrates via the novel P-enolpyruvate (PEP)-glyoxylate cycle, in which two PEP molecules are oxidized by means of acetyl coenzyme A, citrate, glyoxylate, and oxaloacetate to CO₂, and one PEP is regenerated. Key reactions are the constituents of the glyoxylate shunt and PEP carboxykinase, whose conjoint operation in this bi-functional catabolic and anabolic cycle is in sharp contrast to their generally recognized functions in anaplerosis and gluconeogenesis, respectively. Parallel operation of the PEP-glyoxylate cycle and the tricarboxylic acid cycle was identified in the bacterium Escherichia coli under conditions of glucose hunger in a slow-growing continuous culture. Because the PEP-glyoxylate cycle was also active in glucose excess batch cultures of an NADPH-overproducing phosphoglucose isomerase mutant, one function of this new central pathway may be the decoupling of catabolism from NADPH formation that would otherwise occur in the tricarboxylic acid cycle.

Received for publication, July 22, 2003 , and in revised form, August 12, 2003.

^* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Institute of Biotechnology, ETH Zürich, CH-8093 Zürich, Switzerland. Tel.: 411-633-3672; Fax: 411-633-1051; E-mail: sauer{at}biotech.biol.ethz.ch.

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