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.
|Superclasses:||Generation of Precursor Metabolites and Energy → Fermentation → Acetyl-CoA Fermentation to Butanoate|
Expected Taxonomic Range: Firmicutes
The Gram-positive bacterium Clostridium kluyveri is a non-saccharolytic anaerobic organism that can ferment ethanol and acetate to butanoate, hexanoate (caproate), and molecular hydrogen [Barker45, Bornstein48, Smith85]. In additon, this organism can utilize succinate , crotonate, vinylacetate, and 4-hydroxybutanoate [Kenealy85].
In this pathway, acetyl-CoA, which is derived from ethanol (see ethanol degradation I) can be processed in two routes. In the first route, acetyl-CoA is converted to acetate via acetyl phosphate. This conversion generates ATP, which is required for growth, by substrate-level phosphorylation [Thauer68]. In the second route, the reducing power which accumulates during the conversion of ethanol to acetyl-CoA is dispensed via a cycle that results in the excretion of butanoate (or hexanoate). The cycle starts with the condensation of two acetyl-CoA molecules to form acetoacetyl-CoA. This compund then proceeds in a cycle via the intermediates (R)-3-hydroxybutanoyl-CoA and crotonyl-CoA, forming butanoyl-CoA.
The later reacts with acetate via a transacylation reaction. Acetate is acylated to acetyl-CoA, while butanoyl-CoA is converted to butanoate, which is secreted from the cell. The acetyl-CoA that is formed can re-enter the pathway at the condensation step. Thus, the four electrons obtained from the oxidation of ethanol are balanced with the four necessary to reduce the four-carbon moiety formed from one ethanol and one acetate [Smith85].
The same cycle can operate with different CoA donors for the condensation reaction. When propanoyl-CoA or butanoyl-CoA are the donors, the cycle intermediates are different, and the secreted compound is not butyrate but pentanoate or hexanoate, respectively.
A very similar pathway has been described in a related organism, Eubacterium pyruvativorans. The only difference is that the source of acetyl-CoA in this organism is not ethanol, but rather pyruvate, derived from amino acids [Wallace04].
The main difference between this pathway and the one described in pyruvate fermentation to butanoate is the last step. In the other pathway, butanoyl-CoA is converted to butanoate in an energy conserving route via butanoyl phosphate. In this pathway, the conversion is a single-step transacylation reaction catalyzed by acetate CoA-transferase. This reaction yields the CoA donor for a subsequent condensation reaction, and is thus responsible for the cyclical nature of this pathway.
Subpathways: acetate formation from acetyl-CoA I
Barker45: Barker HA, Kamen MD, Bornstein BT (1945). "The Synthesis of Butyric and Caproic Acids from Ethanol and Acetic Acid by Clostridium Kluyveri." Proc Natl Acad Sci U S A 31(12);373-81. PMID: 16588706
Wallace04: Wallace RJ, Chaudhary LC, Miyagawa E, McKain N, Walker ND (2004). "Metabolic properties of Eubacterium pyruvativorans, a ruminal 'hyper-ammonia-producing' anaerobe with metabolic properties analogous to those of Clostridium kluyveri." Microbiology 150(Pt 9);2921-30. PMID: 15347751
Aceti88: Aceti DJ, Ferry JG (1988). "Purification and characterization of acetate kinase from acetate-grown Methanosarcina thermophila. Evidence for regulation of synthesis." J Biol Chem 1988;263(30);15444-8. PMID: 2844814
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
Atteia06: Atteia A, van Lis R, Gelius-Dietrich G, Adrait A, Garin J, Joyard J, Rolland N, Martin W (2006). "Pyruvate formate-lyase and a novel route of eukaryotic ATP synthesis in Chlamydomonas mitochondria." J Biol Chem 281(15);9909-18. PMID: 16452484
Bergmeyer63: Bergmeyer, H.U., Holz, G., Klotzsch, H., Lang, G. (1963). "[Phosphotransacetylase from Clostridium kluyveri. Culture of the bacterium, isolation, crystallization and properties of the enzyme.]." Biochem Z 338;114-21. PMID: 14087284
Bock99: Bock AK, Glasemacher J, Schmidt R, Schonheit P (1999). "Purification and characterization of two extremely thermostable enzymes, phosphate acetyltransferase and acetate kinase, from the hyperthermophilic eubacterium Thermotoga maritima." J Bacteriol 1999;181(6);1861-7. PMID: 10074080
Bologna10: Bologna FP, Campos-Bermudez VA, Saavedra DD, Andreo CS, Drincovich MF (2010). "Characterization of Escherichia coli EutD: a phosphotransacetylase of the ethanolamine operon." J Microbiol 48(5);629-36. PMID: 21046341
Boynton96a: Boynton ZL, Bennett GN, Rudolph FB (1996). "Cloning, sequencing, and expression of genes encoding phosphotransacetylase and acetate kinase from Clostridium acetobutylicum ATCC 824." Appl Environ Microbiol 1996;62(8);2758-66. PMID: 8702268
CamposBermudez10: Campos-Bermudez VA, Bologna FP, Andreo CS, Drincovich MF (2010). "Functional dissection of Escherichia coli phosphotransacetylase structural domains and analysis of key compounds involved in activity regulation." FEBS J 277(8);1957-66. PMID: 20236319
Chae11: Chae, Lee (2011). "The functional annotation of protein sequences was performed by the in-house Ensemble Enzyme Prediction Pipeline (E2P2, version 1.0). E2P2 systematically integrates results from three molecular function annotation algorithms using an ensemble classification scheme. For a given genome, all protein sequences are submitted as individual queries against the base-level annotation methods. The individual methods rely on homology transfer to annotate protein sequences, using single sequence (BLAST, E-value cutoff <= 1e-30, subset of SwissProt 15.3) and multiple sequence (Priam, November 2010; CatFam, version 2.0, 1% FDR profile library) models of enzymatic functions. The base-level predictions are then integrated into a final set of annotations using an average weighted integration algorithm, where the weight of each prediction from each individual method was determined via a 0.632 bootstrap process over 1000 rounds of testing. The training and testing data for E2P2 and the BLAST reference database were drawn from protein sequences with experimental support of existence, compiled from SwissProt release 15.3."
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
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
Denger09: Denger K, Mayer J, Buhmann M, Weinitschke S, Smits TH, Cook AM (2009). "Bifurcated degradative pathway of 3-sulfolactate in Roseovarius nubinhibens ISM via sulfoacetaldehyde acetyltransferase and (S)-cysteate sulfolyase." J Bacteriol 191(18);5648-56. PMID: 19581363
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