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MetaCyc Pathway: pyruvate fermentation to butanoate
Inferred from experiment

Enzyme View:

Pathway diagram: pyruvate fermentation to butanoate

This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Synonyms: central fermentation pathway, acetobutylicum fermentation, pyruvate fermentation to butyrate

Superclasses: Generation of Precursor Metabolites and EnergyFermentationPyruvate Fermentation

Some taxa known to possess this pathway include : Butyrivibrio fibrisolvens, Clostridium acetobutylicum, Clostridium acetobutylicum ATCC 824, Clostridium beijerinckii, Clostridium pasteurianum

Expected Taxonomic Range: Firmicutes, Proteobacteria

Butyrivibrio fibrisolvens is a prevailing butyrate producer in the rumen, and is present in the intestines of humans, dogs, and cats [Asanuma05]. Clostridium acetobutylicum is a Gram-positive anaerobe of commercial importance, capable of fermenting a variety of sugars to solvents and acids. In continuous culture, Clostridium acetobutylicum can be maintained in three different stable metabolic states [Girbal95]: acidogenic (production of acetate and butanoate) when grown at neutral pH on glucose, solventogenic (production of acetone, n-butanol and ethanol) when grown at low pH on glucose, and alcohologenic (formation of n-butanol and ethanol but not acetone) when grown at neutral pH under conditions of high NAD(P)H availability. Despite numerous physiological studies, it is still unclear how the metabolic switch from acid to solvent production is regulated at the molecular level [Green98]. Once this metabolic transition has been initiated, most of the excreted acids are taken up and converted into solvents

During acidogenic growth Clostridium acetobutylicum produces butanoate via the intermediates acetyl-CoA, acetoacetyl-CoA, and butanoyl-CoA. The pathway from acetyl-CoA to butanoyl-CoA is a major carbon metabolism channel and in Clostridium acetobutylicum contains the branch points to solventogenesis and acidogenesis.

The pathway starts with acetyl-CoA C-acetyltransferase, which catalyzes the condensation of two acetyl-CoA molecules to form acetoacetyl-CoA [Wiesenborn88]. Acetoacetyl-CoA is converted to (S)-3-hydroxybutanoyl-CoA by the NAD-dependent (S)-3-hydroxybutyryl-CoA dehydrogenase [Colby92]. 3-hydroxybutyryl-CoA dehydratase and butanoyl-CoA dehydrogenase continue, forming crotonyl-CoA and butanoyl-CoA [Waterson72, Boynton96]. The final two-step conversion of butanoyl-CoA to butanoate is an important source of energy for the cells, as ATP is generated. This two step conversion is catalyzed by phosphotransbutyrylase and butyrate kinase [Wiesenborn89, Hartmanis87].

Under normal fermentation conditions the reactions run solely in the direction of butanoate formation.

Superpathways: L-glutamate degradation VII (to butanoate), superpathway of Clostridium acetobutylicum acidogenic fermentation, superpathway of Clostridium acetobutylicum acidogenic and solventogenic fermentation

Variants: pyruvate fermentation to acetate and alanine, pyruvate fermentation to acetate and lactate I, pyruvate fermentation to acetate and lactate II, pyruvate fermentation to acetate I, pyruvate fermentation to acetate II, pyruvate fermentation to acetate III, pyruvate fermentation to acetate IV, pyruvate fermentation to acetate V, pyruvate fermentation to acetate VI, pyruvate fermentation to acetate VII, pyruvate fermentation to acetate VIII, pyruvate fermentation to acetone, pyruvate fermentation to butanol I, pyruvate fermentation to butanol II, pyruvate fermentation to ethanol I, pyruvate fermentation to ethanol II, pyruvate fermentation to ethanol III, pyruvate fermentation to hexanol, pyruvate fermentation to isobutanol (engineered), pyruvate fermentation to lactate, pyruvate fermentation to opines, pyruvate fermentation to propanoate I, pyruvate fermentation to propanoate II (acrylate pathway), superpathway of Clostridium acetobutylicum solventogenic fermentation, superpathway of fermentation (Chlamydomonas reinhardtii)

Revised 08-May-2006 by Caspi R, SRI International


Asanuma05: Asanuma N, Ishiwata M, Yoshii T, Kikuchi M, Nishina Y, Hino T (2005). "Characterization and transcription of the genes involved in butyrate production in Butyrivibrio fibrisolvens type I and II strains." Curr Microbiol 51(2);91-4. PMID: 15991056

Bermejo98: Bermejo LL, Welker NE, Papoutsakis ET (1998). "Expression of Clostridium acetobutylicum ATCC 824 genes in Escherichia coli for acetone production and acetate detoxification." Appl Environ Microbiol 1998;64(3);1079-85. PMID: 9501448

Boynton96: Boynton ZL, Bennet GN, Rudolph FB (1996). "Cloning, sequencing, and expression of clustered genes encoding beta-hydroxybutyryl-coenzyme A (CoA) dehydrogenase, crotonase, and butyryl-CoA dehydrogenase from Clostridium acetobutylicum ATCC 824." J Bacteriol 1996;178(11);3015-24. PMID: 8655474

Colby92: Colby GD, Chen JS (1992). "Purification and properties of 3-hydroxybutyryl-coenzyme A dehydrogenase from Clostridium beijerinckii ("Clostridium butylicum") NRRL B593." Appl Environ Microbiol 58(10);3297-302. PMID: 1444364

Girbal95: Girbal L., Croux C., Vasconcelos I., Soucaille P. (1995). "Regulation of metabolic shifts in Clostridium acetobutylicum ATCC824." FEMS Microbiol. Rev. 17:287-297.

Green98: Green EM, Bennett GN (1998). "Genetic Manipulation of Acid and Solvent Formation in Clostridium acetobutylicum ATCC 824." Biotechnology and Bioengineering 58: 215-221. PMID: 10191392

Hartmanis84: Hartmanis MG, Gatenbeck S (1984). "Intermediary Metabolism in Clostridium acetobutylicum: Levels of Enzymes Involved in the Formation of Acetate and Butyrate." Appl Environ Microbiol 47(6);1277-1283. PMID: 16346566

Hartmanis87: Hartmanis MG (1987). "Butyrate kinase from Clostridium acetobutylicum." J Biol Chem 1987;262(2);617-21. PMID: 3027059

Waterson72: Waterson RM, Castellino FJ, Hass GM, Hill RL (1972). "Purification and characterization of cortonase from Clostridium acetobutylicum." J Biol Chem 1972;247(16);5266-71. PMID: 5057466

Wiesenborn88: Wiesenborn DP, Rudolph FB, Papoutsakis ET (1988). "Thiolase from Clostridium acetobutylicum ATCC 824 and Its Role in the Synthesis of Acids and Solvents." Appl Environ Microbiol 54(11);2717-2722. PMID: 16347774

Wiesenborn89: Wiesenborn DP, Rudolph FB, Papoutsakis ET (1989). "Phosphotransbutyrylase from Clostridium acetobutylicum ATCC 824 and its role in acidogenesis." Appl Environ Microbiol 1989;55(2);317-22. PMID: 2719475

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

Alber06: Alber BE, Spanheimer R, Ebenau-Jehle C, Fuchs G (2006). "Study of an alternate glyoxylate cycle for acetate assimilation by Rhodobacter sphaeroides." Mol Microbiol 61(2);297-309. PMID: 16856937

Bairoch93a: Bairoch A, Boeckmann B (1993). "The SWISS-PROT protein sequence data bank, recent developments." Nucleic Acids Res. 21:3093-3096. PMID: 8332529

Barker82: Barker HA, Kahn JM, Hedrick L (1982). "Pathway of lysine degradation in Fusobacterium nucleatum." J Bacteriol 152(1);201-7. PMID: 6811551

Beh93: Beh M, Strauss G, Huber R, Stetter K-O, Fuchs G (1993). "Enzymes of the reductive citric acid cycle in the autotrophic eubacterium Aquifex pyrophilus and in the archaebacterium Thermoproteus neutrophilus." Arch Microbiol 160: 306-311.

Berg07: Berg IA, Kockelkorn D, Buckel W, Fuchs G (2007). "A 3-hydroxypropionate/4-hydroxybutyrate autotrophic carbon dioxide assimilation pathway in Archaea." Science 318(5857);1782-6. PMID: 18079405

Blamey93: Blamey JM, Adams MW (1993). "Purification and characterization of pyruvate ferredoxin oxidoreductase from the hyperthermophilic archaeon Pyrococcus furiosus." Biochim Biophys Acta 1161(1);19-27. PMID: 8380721

Blamey94: Blamey JM, Adams MW (1994). "Characterization of an ancestral type of pyruvate ferredoxin oxidoreductase from the hyperthermophilic bacterium, Thermotoga maritima." Biochemistry 1994;33(4);1000-7. PMID: 8305426

Blaschkowski82: Blaschkowski HP, Neuer G, Ludwig-Festl M, Knappe J (1982). "Routes of flavodoxin and ferredoxin reduction in Escherichia coli. CoA-acylating pyruvate: flavodoxin and NADPH: flavodoxin oxidoreductases participating in the activation of pyruvate formate-lyase." Eur J Biochem 123(3);563-9. PMID: 7042345

BRENDA14: BRENDA team (2014). Imported from BRENDA version existing on Aug 2014.

Cary88: Cary JW, Petersen DJ, Papoutsakis ET, Bennett GN (1988). "Cloning and expression of Clostridium acetobutylicum phosphotransbutyrylase and butyrate kinase genes in Escherichia coli." J Bacteriol 1988;170(10):4613-4618. PMID: 2844725

Catalanotti12: Catalanotti C, Dubini A, Subramanian V, Yang W, Magneschi L, Mus F, Seibert M, Posewitz MC, Grossman AR (2012). "Altered fermentative metabolism in Chlamydomonas reinhardtii mutants lacking pyruvate formate lyase and both pyruvate formate lyase and alcohol dehydrogenase." Plant Cell 24(2);692-707. PMID: 22353371

Chen94: Chen D, Swenson RP (1994). "Cloning, sequence analysis, and expression of the genes encoding the two subunits of the methylotrophic bacterium W3A1 electron transfer flavoprotein." J Biol Chem 269(51);32120-30. PMID: 7798207

Conrad74: Conrad RS, Massey LK, Sokatch JR (1974). "D- and L-isoleucine metabolism and regulation of their pathways in Pseudomonas putida." J Bacteriol 118(1);103-11. PMID: 4150713

Daum98: Daum G, Lees ND, Bard M, Dickson R (1998). "Biochemistry, cell biology and molecular biology of lipids of Saccharomyces cerevisiae." Yeast 1998;14(16);1471-510. PMID: 9885152

Dekishima11: Dekishima Y, Lan EI, Shen CR, Cho KM, Liao JC (2011). "Extending Carbon Chain Length of 1-Butanol Pathway for 1-Hexanol Synthesis from Glucose by Engineered Escherichia coli." J Am Chem Soc 133(30);11399-401. PMID: 21707101

Duncombe76: Duncombe GR, Frerman FE (1976). "Molecular and catalytic properties of the acetoacetyl-coenzyme A thiolase of Escherichia coli." Arch Biochem Biophys 1976;176(1);159-70. PMID: 9904

Engel81: Engel, P.C. (1981). "Butyryl-CoA dehydrogenase from Megaspharea elsdenii." Methods Enzymol. 71:359-366.

Green54: Green DE, Mii S, Mahler HR, Bock RM (1954). "Studies on the fatty acid oxidizing system of animal tissues. III. Butyryl coenzyme A dehydrogenase." J Biol Chem 206(1);1-12. PMID: 13130521

Haapalainen07: Haapalainen AM, Merilainen G, Pirila PL, Kondo N, Fukao T, Wierenga RK (2007). "Crystallographic and kinetic studies of human mitochondrial acetoacetyl-CoA thiolase: the importance of potassium and chloride ions for its structure and function." Biochemistry 46(14);4305-21. PMID: 17371050

Hartmanis82: Hartmanis MG, Stadtman TC (1982). "Isolation of a selenium-containing thiolase from Clostridium kluyveri: identification of the selenium moiety as selenomethionine." Proc Natl Acad Sci U S A 79(16);4912-6. PMID: 6956900

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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
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