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MetaCyc Pathway: Methanobacterium thermoautotrophicum biosynthetic metabolism
Inferred from experiment

Pathway diagram: Methanobacterium thermoautotrophicum biosynthetic metabolism

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

Superclasses: Biosynthesis

Some taxa known to possess this pathway include : Methanobacterium thermoautotrophicum Marburg, Methanothermobacter thermautotrophicus, Methanothermobacter thermautotrophicus Delta H, Methanothermobacter thermautotrophicus Winter

Expected Taxonomic Range: Archaea

Methanothermobacter thermautotrophicus is a thermophilic methanogenic archaebacterium. The organism is an autotrophic anaerobe and can grow on a gas mixture of CO2 and H2 as its carbon and energy sources, respectively.

CO2 fixation:

Methanothermobacter thermautotrophicus does not possess the Calvin cycle nor a full reductive tricarboxylic acid cycle. Instead, it fixes CO2 via several alternative routes.

The first, and main route, is the reductive acetyl coenzyme A pathway. The product of this pathway, acetyl-CoA, is a central intermediate in this organism and is used for all subsequent biosynthetic pathways [Fuchs80, Jansen82].

A second CO2 molecule is incorporated by the pyruvate synthase complex, which converts acetyl-CoA to pyruvate.

A third CO2 molecule is incorporated by pyruvate carboxylase, which converts pyruvate to oxaloacetate [Mukhopadhyay98]. This enzyme accepts only hydrogen carbonate molecules, but Methanothermobacter thermautotrophicus Delta H possesses a carbonic anhydrase enzyme, which can convert CO2 into hydrogen carbonate [Smith99a].

Finally, a fourth CO2 molecule is incorporated during the carboxylation of phosphoenolpyruvate to oxaloacetate, which is carried by phosphoenolpyruvate carboxylase [Patel04].

Amino acid biosynthesis:

pyruvate can be converted directly to L-alanine. oxaloacetate can be processed directly to L-aspartate, ot it can lead into an incomplete reductive TCA cycle that ends at L-glutamate [Fuchs80].

Carbohydrate biosynthesis:

phosphoenolpyruvate leads to a gluconeogenesis pathway that ends at β-D-glucose 6-phosphate, furnishing the cell with all of the glycolysis/gluconeogenesis intermediates that are required for biosynthesis [Fuchs80],

Phospholipid biosynthesis:

Like other archaebacteria, the main phospholipid in Methanothermobacter thermautotrophicus membranes is unsaturated archaetidylserine. This phospholipid is synthesized from a sn-glycerol 1-phosphate backbone (produced from glycerone phosphate) and geranylgeranyl diphosphate, which is produced from acetyl-CoA.

Most of the enzymes catalyzing these pathways have not been identified or characterized. The pathways were predicted using stable isotope labeling and NMR spectroscopy experiments [Jansen82, Evans86].

Subpathways: geranylgeranyl diphosphate biosynthesis, trans, trans-farnesyl diphosphate biosynthesis, mevalonate pathway I, superpathway of geranylgeranyldiphosphate biosynthesis I (via mevalonate), archaetidylserine and archaetidylethanolamine biosynthesis, L-alanine biosynthesis II, L-aspartate biosynthesis, incomplete reductive TCA cycle, gluconeogenesis II (Methanobacterium thermoautotrophicum), reductive acetyl coenzyme A pathway, CDP-archaeol biosynthesis

Created 05-Mar-2009 by Caspi R, SRI International


Evans86: Evans JN, Raleigh DP, Tolman CJ, Roberts MF (1986). "13C NMR spectroscopy of Methanobacterium thermoautotrophicum. Carbon fluxes and primary metabolic pathways." J Biol Chem 261(35);16323-31. PMID: 3782122

Fuchs80: Fuchs, G., Stupperich, E. (1980). "Acetyl CoA, a central intermediate of autotrophic CO2 fixation in Methanobacterium thermoautotrophicum." Archives of Microbiology 127(3): 267-272.

Jansen82: Jansen, K., Stupperich, E., Fuchs, G. (1982). "Carbohydrate synthesis from acetyl CoA in the autotroph Methanobacterium thermoautotrophicum." Archives of Microbiology 132(4): 355-364.

Mukhopadhyay98: Mukhopadhyay B, Stoddard SF, Wolfe RS (1998). "Purification, regulation, and molecular and biochemical characterization of pyruvate carboxylase from Methanobacterium thermoautotrophicum strain deltaH." J Biol Chem 273(9);5155-66. PMID: 9478969

Patel04: Patel HM, Kraszewski JL, Mukhopadhyay B (2004). "The phosphoenolpyruvate carboxylase from Methanothermobacter thermautotrophicus has a novel structure." J Bacteriol 186(15);5129-37. PMID: 15262949

Smith99a: Smith KS, Ferry JG (1999). "A plant-type (beta-class) carbonic anhydrase in the thermophilic methanoarchaeon Methanobacterium thermoautotrophicum." J Bacteriol 181(20);6247-53. PMID: 10515911

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

Abbe83: Abbe K, Takahashi S, Yamada T (1983). "Purification and properties of pyruvate kinase from Streptococcus sanguis and activator specificity of pyruvate kinase from oral streptococci." Infect Immun 39(3);1007-14. PMID: 6840832

Aharoni03: Aharoni A, Giri AP, Deuerlein S, Griepink F, de Kogel WJ, Verstappen FW, Verhoeven HA, Jongsma MA, Schwab W, Bouwmeester HJ (2003). "Terpenoid metabolism in wild-type and transgenic Arabidopsis plants." Plant Cell 15(12);2866-84. PMID: 14630967

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

Albery76: Albery WJ, Knowles JR (1976). "Free-energy profile of the reaction catalyzed by triosephosphate isomerase." Biochemistry 15(25);5627-31. PMID: 999838

Allen64: Allen, S.H., Kellermeyer, R.W., Ssjernholm, R.L., Wood, H.G. (1964). "Purification and properties of enzymes involved in the propionic acid fermentation." J Bacteriol 87;171-87. PMID: 14102852

Alvarez98: Alvarez M, Zeelen JP, Mainfroid V, Rentier-Delrue F, Martial JA, Wyns L, Wierenga RK, Maes D (1998). "Triose-phosphate isomerase (TIM) of the psychrophilic bacterium Vibrio marinus. Kinetic and structural properties." J Biol Chem 273(4);2199-206. PMID: 9442062

Anderson75: Anderson L.E., Heinrikson R.L., Noyes C. "Chloroplast and cytoplasmic enzymes." Arch. Biochem. Biophys. (1975) 169:262-268.

Anderson89a: Anderson MS, Muehlbacher M, Street IP, Proffitt J, Poulter CD (1989). "Isopentenyl diphosphate:dimethylallyl diphosphate isomerase. An improved purification of the enzyme and isolation of the gene from Saccharomyces cerevisiae." J Biol Chem 1989;264(32);19169-75. PMID: 2681212

Anderson89b: Anderson MS, Yarger JG, Burck CL, Poulter CD (1989). "Farnesyl diphosphate synthetase. Molecular cloning, sequence, and expression of an essential gene from Saccharomyces cerevisiae." J Biol Chem 1989;264(32);19176-84. PMID: 2681213

Ashizawa91: Ashizawa K, McPhie P, Lin KH, Cheng SY (1991). "An in vitro novel mechanism of regulating the activity of pyruvate kinase M2 by thyroid hormone and fructose 1, 6-bisphosphate." Biochemistry 30(29);7105-11. PMID: 1854723

Bailey99: Bailey DL, Fraser ME, Bridger WA, James MN, Wolodko WT (1999). "A dimeric form of Escherichia coli succinyl-CoA synthetase produced by site-directed mutagenesis." J Mol Biol 285(4);1655-66. PMID: 9917403

Baldwin78: Baldwin SA, Perham RN (1978). "Novel kinetic and structural properties of the class-I D-fructose 1,6-bisphosphate aldolase from Escherichia coli (Crookes' strain)." Biochem J 1978;169(3);643-52. PMID: 348198

Baldwin78a: Baldwin SA, Perham RN, Stribling D (1978). "Purification and characterization of the class-II D-fructose 1,6-bisphosphate aldolase from Escherichia coli (Crookes' strain)." Biochem J 1978;169(3);633-41. PMID: 417719

Bard81: Bard M, Downing JF (1981). "Genetic and biochemical aspects of yeast sterol regulation involving 3-hydroxy-3-methylglutaryl coenzyme A reductase." J Gen Microbiol 1981;125(Pt 2);415-20. PMID: 7033470

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

Barnard81: Barnard GF, Popjak G (1981). "Human liver prenyltransferase and its characterization." Biochim Biophys Acta 661(1);87-99. PMID: 7295734

Baughn09: Baughn AD, Garforth SJ, Vilcheze C, Jacobs WR (2009). "An anaerobic-type alpha-ketoglutarate ferredoxin oxidoreductase completes the oxidative tricarboxylic acid cycle of Mycobacterium tuberculosis." PLoS Pathog 5(11);e1000662. PMID: 19936047

Baveja86: Baveja UK, Jyoti AS, Kaur M, Agarwal DS, Anand BS, Nanda R (1986). "Isoenzyme studies of Giardia lamblia isolated from symptomatic cases." Aust J Exp Biol Med Sci 64 ( Pt 2);119-26. PMID: 2943257

Beaucamp97: Beaucamp N, Hofmann A, Kellerer B, Jaenicke R (1997). "Dissection of the gene of the bifunctional PGK-TIM fusion protein from the hyperthermophilic bacterium Thermotoga maritima: design and characterization of the separate triosephosphate isomerase." Protein Sci 1997;6(10);2159-65. PMID: 9336838

Beaucamp97a: Beaucamp N, Schurig H, Jaenicke R (1997). "The PGK-TIM fusion protein from Thermotoga maritima and its constituent parts are intrinsically stable and fold independently." Biol Chem 1997;378(7);679-85. PMID: 9278147

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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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