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Escherichia coli K-12 substr. MG1655 Pathway: mixed acid fermentation
Inferred from experiment

Pathway diagram: mixed acid fermentation

If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Locations of Mapped Genes:

Schematic showing all replicons, marked with selected genes

Genetic Regulation Schematic

Genetic regulation schematic for mixed acid fermentation

Synonyms: fermentation

Superclasses: Generation of Precursor Metabolites and EnergyFermentation

Escherichia coli, a facultative anaerobe, is capable of mediating the mixed acid fermentation and thereby, in the absence of any of the exogenous electron acceptors that it can utilize (oxygen, fumarate, nitrate, nitrite, trimethylamine oxide, or dimethyl sulfoxide), able to grow on a variety of compounds including hexoses, hexitols, hexonic acids, and hexuronic acids.

E. coli ferments only when exogenous electron acceptors are not available. In the shift from exogenous electron-dependent growth to the mixed acid fermentation, pyruvate dehydrogenase is no longer synthesized. Instead, pyruvate formate-lyase, which cleaves pyruvate nonoxidatively to formate and acetyl-CoA, is made. Formate is excreted as formic acid. Some of the acetyl-CoA enters the remnant of the TCA cycle, which terminates at 2-oxoglutarate because 2-oxoglutarate dehydrogenase synthesis is repressed. In spite of such repression, all components of the TCA cycle and therefore its essential precursor metabolites, continue to be made by the now two arms of the cycle: one, leading to 2-oxoglutarate, still oxidatively, and the other, leading to succinate, now reductively. Succinate is excreted as succinic acid. The acetyl-CoA not needed for these purposes is metabolized via acetylphosphate to acetate, thereby generating ATP. The acetate so formed is excreted as acetic acid.

During the shift to the mixed acid fermentation, three additional enzymes are made: 1) a lactate dehydrogenase, which reduces pyruvate to lactate that is excreted as lactic acid; 2) an ethanol dehydrogenase, which reduces acetyl-CoA to acetaldehyde and subsequently to ethanol, which is excreted; 3) formic hydrogen lyase, which cleaves formate to CO2 and H2. The multiplicity of possible endproducts of fermentation with differing oxidation states and acidity permits E. coli to maintain redox balance and therefore to grow fermentatively on a broader range of substrates than would otherwise be possible. When growing on a more reduced substrate such as glucitol, greater quantities of more reduced endproducts such as ethanol, acetic acid, and lactic acid are produced; on more oxidized substrates such as glucuronate, more of the oxidized endproducts, succinic acid and formic acid, are made. Conversion of formate to H2 and CO2 is regulated by pH.

Review: Bock, A. and Sawers, G., Chapter 18: Fermentation, in [Neidhardt96]

Citations: [Gupta89, Dawes56]

Created 03-May-1994 by Riley M, Marine Biological Laboratory
Revised 28-Jan-2009 by Ingraham JL, UC Davis


Dawes56: Dawes EA, Foster SM (1956). "The formation of ethanol in Escherichia coli." Biochim Biophys Acta 22(2):253-265. PMID: 13382840

Gupta89: Gupta S, Clark DP (1989). "Escherichia coli derivatives lacking both alcohol dehydrogenase and phosphotransacetylase grow anaerobically by lactate fermentation." J Bacteriol 171(7);3650-5. PMID: 2661531

Neidhardt96: Neidhardt FC, Curtiss III R, Ingraham JL, Lin ECC, Low Jr KB, Magasanik B, Reznikoff WS, Riley M, Schaechter M, Umbarger HE "Escherichia coli and Salmonella, Cellular and Molecular Biology, Second Edition." American Society for Microbiology, Washington, D.C., 1996.

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Abaibou97: Abaibou H, Giordano G, Mandrand-Berthelot MA (1997). "Suppression of Escherichia coli formate hydrogenlyase activity by trimethylamine N-oxide is due to drainage of the inducer formate." Microbiology 143 ( Pt 8);2657-64. PMID: 9274019

Acebron09: Acebron SP, Martin I, del Castillo U, Moro F, Muga A (2009). "DnaK-mediated association of ClpB to protein aggregates. A bichaperone network at the aggregate surface." FEBS Lett 583(18);2991-6. PMID: 19698713

Al04: Al Zaid Siddiquee K, Arauzo-Bravo MJ, Shimizu K (2004). "Metabolic flux analysis of pykF gene knockout Escherichia coli based on 13C-labeling experiments together with measurements of enzyme activities and intracellular metabolite concentrations." Appl Microbiol Biotechnol 63(4);407-17. PMID: 12802531

Al12: Al Mamun AA, Lombardo MJ, Shee C, Lisewski AM, Gonzalez C, Lin D, Nehring RB, Saint-Ruf C, Gibson JL, Frisch RL, Lichtarge O, Hastings PJ, Rosenberg SM (2012). "Identity and function of a large gene network underlying mutagenic repair of DNA breaks." Science 338(6112);1344-8. PMID: 23224554

Alam89: Alam KY, Clark DP (1989). "Anaerobic fermentation balance of Escherichia coli as observed by in vivo nuclear magnetic resonance spectroscopy." J Bacteriol 171(11);6213-7. PMID: 2681156

Amarneh05: Amarneh B, Vik SB (2005). "Direct transfer of NADH from malate dehydrogenase to complex I in Escherichia coli." Cell Biochem Biophys 42(3);251-61. PMID: 15976458

Anderson88: Anderson DH, Duckworth HW (1988). "In vitro mutagenesis of Escherichia coli citrate synthase to clarify the locations of ligand binding sites." J Biol Chem 1988;263(5);2163-9. PMID: 3276685

Apostolakos82: Apostolakos D, Menter PA, Rampsch BJ, Reeves HC, Birge EA "Genetic map position of the cistron coding for isocitrate dehydrogenase in Escherichia coli K-12." Current Microbiology 1982;7:45-47.

Arifuzzaman06: Arifuzzaman M, Maeda M, Itoh A, Nishikata K, Takita C, Saito R, Ara T, Nakahigashi K, Huang HC, Hirai A, Tsuzuki K, Nakamura S, Altaf-Ul-Amin M, Oshima T, Baba T, Yamamoto N, Kawamura T, Ioka-Nakamichi T, Kitagawa M, Tomita M, Kanaya S, Wada C, Mori H (2006). "Large-scale identification of protein-protein interaction of Escherichia coli K-12." Genome Res 16(5);686-91. PMID: 16606699

Aristarkhov96: Aristarkhov A, Mikulskis A, Belasco JG, Lin EC (1996). "Translation of the adhE transcript to produce ethanol dehydrogenase requires RNase III cleavage in Escherichia coli." J Bacteriol 178(14);4327-32. PMID: 8763968

Avison01: Avison MB, Horton RE, Walsh TR, Bennett PM (2001). "Escherichia coli CreBC is a global regulator of gene expression that responds to growth in minimal media." J Biol Chem 276(29);26955-61. PMID: 11350954

Axley88: Axley MJ, Stadtman TC (1988). "Anaerobic induction of Escherichia coli formate dehydrogenase (hydrogenase-linked) is enhanced by gyrase inactivation." Proc Natl Acad Sci U S A 85(4);1023-7. PMID: 2829213

Axley90: Axley MJ, Grahame DA, Stadtman TC (1990). "Escherichia coli formate-hydrogen lyase. Purification and properties of the selenium-dependent formate dehydrogenase component." J Biol Chem 1990;265(30);18213-8. PMID: 2211698

Axley91: Axley MJ, Grahame DA (1991). "Kinetics for formate dehydrogenase of Escherichia coli formate-hydrogenlyase." J Biol Chem 266(21);13731-6. PMID: 1906883

Bagramyan02: Bagramyan K, Mnatsakanyan N, Poladian A, Vassilian A, Trchounian A (2002). "The roles of hydrogenases 3 and 4, and the F0F1-ATPase, in H2 production by Escherichia coli at alkaline and acidic pH." FEBS Lett 516(1-3);172-8. PMID: 11959127

Bagramyan03: Bagramyan K, Trchounian A (2003). "Structural and functional features of formate hydrogen lyase, an enzyme of mixed-acid fermentation from Escherichia coli." Biochemistry (Mosc) 68(11);1159-70. PMID: 14640957

Bairoch93: Bairoch A, Boeckmann B (1993). "The SWISS-PROT protein sequence data bank, recent developments." Nucleic Acids Res. 21:3093-3096. PMID: 8332529

Barak96: Barak R, Giebel I, Eisenbach M (1996). "The specificity of fumarate as a switching factor of the bacterial flagellar motor." Mol Microbiol 19(1);139-44. PMID: 8821943

Barak98: Barak R, Abouhamad WN, Eisenbach M (1998). "Both acetate kinase and acetyl coenzyme A synthetase are involved in acetate-stimulated change in the direction of flagellar rotation in Escherichia coli." J Bacteriol 1998;180(4);985-8. PMID: 9473056

Becker02a: Becker A, Kabsch W (2002). "X-ray structure of pyruvate formate-lyase in complex with pyruvate and CoA. How the enzyme uses the Cys-418 thiyl radical for pyruvate cleavage." J Biol Chem 277(42);40036-42. PMID: 12163496

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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
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