If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
|Superclasses:||Degradation/Utilization/Assimilation → C1 Compounds Utilization and Assimilation → Formaldehyde Assimilation|
Some taxa known to possess this pathway include : Hyphomicrobium methylovorum GM2 , Hyphomicrobium zavarzinii ZV580 , Methylobacter whittenburyi , Methylobacterium extorquens AM1 , Methylobacterium organophilum , Methylocystis echinoides , Methylocystis minimus , Methylocystis parvus , Methylocystis pyriformis , Methylosinus sporium , Methylosinus trichosporium
Expected Taxonomic Range:
Methanotrophic bacteria oxidize methane and methanol to formaldehyde, which can be assimilated to form intermediates of the central metabolic pathways. These intermediate compounds are subsequently used for biosynthesis [Quayle78, Quayle80, deVries90].
There are two known pathways that are used by methanotrophic bacteria for the assimilation of formaldehyde: the serine pathway (this pathway) and the RuMP cycle (see formaldehyde assimilation II (RuMP Cycle)) [Hanson96a].
In the first reaction of the serine pathway, formaldehyde reacts with glycine to form serine. The reaction is catalyzed by serine hydroxymethyltransferase (SHMT), an enzyme that uses tetrahydropteroyl mono-L-glutamate (THF) as a cofactor. When formaldehyde is bound to it, it forms 5,10-methylenetetrahydropteroyl mono-L-glutamate. During the reaction the formaldehyde is transferred from 5,10-methylenetetrahydropteroyl mono-L-glutamate to the glycine, forming L-serine. Two such enzymes, one for assimilation of formaldehyde and one for biosynthesis of glycine from serine, are known in Methylobacterium extorquens AM1 and Methylobacterium organophilum [OConnor75]. In the next step serine is transaminated with glyoxylate as the amino group acceptor by the enzyme serine-glyoxylate aminotransferase, to produce hydroxypyruvate and glycine (the glycine can be recycled and serve as a substrate for serine hydroxymethyltransferase). Hydroxypyruvate is reduced to glycerate by hydroxypyruvate reductase. glycerate 2-kinase catalyzes the addition of a phosphate group from ATP to produce 2-phosphoglycerate.
At this point there is a split in the pathway. Some of the 2-phosphoglycerate is converted by 2,3-bisphosphoglycerate-dependent phosphoglycerate mutase to 3-phosphoglycerate, which is an intermediate of the central metabolic pathways, and is used for biosynthesis. The rest of the 2-phosphoglycerate is converted by an enolase to phosphoenolpyruvate. phosphoenolpyruvate carboxylase then catalyzes the fixation of carbon dioxide coupled to the conversion of phosphoenolpyruvate to oxaloacetate, which is reduced to malate by malate dehydrogenase (NAD-linked). Malyl coenzyme A is formed in a reaction catalyzed by malate thiokinase and is cleaved by malyl coenzyme A lyase into acetyl coA and glyoxylate. These two enzymes (malate thiokinase and malyl coenzyme A lyase), as well as hydroxypyruvate reductase and glycerate-2-kinase, are uniquely present in methylotrophs that contain the serine pathway [Barta93, Murrell92, Quayle80].
The next part of the pathway is not as well characterized. The fate of the acetyl coenzyme A depends on wheher the organism possesses the enzyme isocitrate lyase, which is a key enzyme of the glyoxylate cycle. If the enzyme is present, acetyl CoA is converted to glyoxylate by the glyoxylate cycle. However, if the enzyme is missing, it is converted by another unknown pathway [deVries90]. In any case, the resulting glyoxylate can serve as substrate for serine-glyoxylate aminotransferase, regenerating glycine and closing the circle.
The net balance of this cycle is the fixation of two mols of formaldehyde and 1 mol of CO2 into 1 mol of 3-phosphoglycerate, which is used for biosynthesis, at the expense of 2 mols ATP and the oxidation of 2 mols of NAD(P)H.
Please note that reaction 18.104.22.168 (catalyzed by serine-glyoxylate aminotransferase) appears twice in the diagram, (once for the reaction L-serine to hydroxypyruvate, and once for the reaction glyoxylate to glycine) even though in reality the two reactions are coupled.
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
Arps93: Arps PJ, Fulton GF, Minnich EC, Lidstrom ME (1993). "Genetics of serine pathway enzymes in Methylobacterium extorquens AM1: phosphoenolpyruvate carboxylase and malyl coenzyme A lyase." J Bacteriol 175(12);3776-83. PMID: 8509332
Beckmann97: Beckmann K, Dzuibany C, Biehler K, Fock H, Hell R, Migge A, Becker TW (1997). "Photosynthesis and fluorescence quenching, and the mRNA levels of plastidic glutamine synthetase or of mitochondrial serine hydroxymethyltransferase (SHMT) in the leaves of the wild-type and of the SHMT-deficient stm mutant of Arabidopsis thaliana in relation to the rate of photorespiration." Planta 202(3);379-86. PMID: 9232907
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.
Berkemeyer98: Berkemeyer M, Scheibe R, Ocheretina O (1998). "A novel, non-redox-regulated NAD-dependent malate dehydrogenase from chloroplasts of Arabidopsis thaliana L." J Biol Chem 273(43);27927-33. PMID: 9774405
Capela01: Capela D, Barloy-Hubler F, Gouzy J, Bothe G, Ampe F, Batut J, Boistard P, Becker A, Boutry M, Cadieu E, Dreano S, Gloux S, Godrie T, Goffeau A, Kahn D, Kiss E, Lelaure V, Masuy D, Pohl T, Portetelle D, Puhler A, Purnelle B, Ramsperger U, Renard C, Thebault P, Vandenbol M, Weidner S, Galibert F (2001). "Analysis of the chromosome sequence of the legume symbiont Sinorhizobium meliloti strain 1021." Proc Natl Acad Sci U S A 98(17);9877-82. PMID: 11481430
Chistoserdova91: Chistoserdova LV, Lidstrom ME (1991). "Purification and characterization of hydroxypyruvate reductase from the facultative methylotroph Methylobacterium extorquens AM1." J Bacteriol 173(22);7228-32. PMID: 1657886
Chistoserdova92: Chistoserdova LV, Lidstrom ME (1992). "Cloning, mutagenesis, and physiological effect of a hydroxypyruvate reductase gene from Methylobacterium extorquens AM1." J Bacteriol 174(1);71-7. PMID: 1729225
Chistoserdova94: Chistoserdova LV, Lidstrom ME (1994). "Genetics of the serine cycle in Methylobacterium extorquens AM1: identification, sequence, and mutation of three new genes involved in C1 assimilation, orf4, mtkA, and mtkB." J Bacteriol 176(23);7398-404. PMID: 7961516
Chistoserdova94a: Chistoserdova LV, Lidstrom ME (1994). "Genetics of the serine cycle in Methylobacterium extorquens AM1: cloning, sequence, mutation, and physiological effect of glyA, the gene for serine hydroxymethyltransferase." J Bacteriol 176(21);6759-62. PMID: 7961431
Chistoserdova94b: Chistoserdova LV, Lidstrom ME (1994). "Genetics of the serine cycle in Methylobacterium extorquens AM1: identification of sgaA and mtdA and sequences of sgaA, hprA, and mtdA." J Bacteriol 176(7);1957-68. PMID: 8144463
Chistoserdova96: Chistoserdova LV, Lidstrom ME (1996). "Molecular characterization of a chromosomal region involved in the oxidation of acetyl-CoA to glyoxylate in the isocitrate-lyase-negative methylotroph Methylobacterium extorquens AM1." Microbiology 142 ( Pt 6);1459-68. PMID: 8704985
Chistoserdova97: Chistoserdova L, Lidstrom ME (1997). "Molecular and mutational analysis of a DNA region separating two methylotrophy gene clusters in Methylobacterium extorquens AM1." Microbiology 143 ( Pt 5);1729-36. PMID: 9168622
Chistoserdova97a: Chistoserdova L, Lidstrom ME (1997). "Identification and mutation of a gene required for glycerate kinase activity from a facultative methylotroph, Methylobacterium extorquens AM1." J Bacteriol 179(15);4946-8. PMID: 9244287
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