MetaCyc Pathway: formaldehyde assimilation I (serine pathway)
Inferred from experiment

Pathway diagram: formaldehyde assimilation I (serine pathway)

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

Superclasses: Degradation/Utilization/AssimilationC1 Compounds Utilization and AssimilationFormaldehyde 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: Bacteria

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)) [Hanson96].

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 (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.

Variants: formaldehyde assimilation II (RuMP Cycle), formaldehyde assimilation III (dihydroxyacetone cycle)

Created 03-Aug-2004 by Caspi R, SRI International


Barta93: Barta TM, Hanson RS "Genetics of methane and methanol oxidation in gram-negative methylotrophic bacteria." Antonie Van Leeuwenhoek 1993-94; 64(2):109-20. PMID: 8092853

deVries90: de Vries GE, Kues U, Stahl U (1990). "Physiology and genetics of methylotrophic bacteria." FEMS Microbiol Rev 6(1);57-101. PMID: 2110811

Hanson96: Hanson, RS, Hanson, ET "Methanotrophic bacteria." Microbiological Reviews(1996) 60(2):439-471.

Murrell92: Murrell JC (1992). "Genetics and molecular biology of methanotrophs." FEMS Microbiol Rev 8(3-4);233-48. PMID: 1515161

OConnor75: O'Connor ML, Hanson RS (1975). "Serine transhydroxymethylase isoenzymes from a facultative methylotroph." J Bacteriol 124(2);985-96. PMID: 241747

Quayle78: Quayle JR, Ferenci T (1978). "Evolutionary aspects of autotrophy." Microbiol Rev 42(2);251-73. PMID: 353476

Quayle80: Quayle JR (1980). "Microbial assimilation of C1 compounds. The Thirteenth CIBA Medal Lecture." Biochem Soc Trans 8(1);1-10. PMID: 6768606

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

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

Angelaccio92: Angelaccio S, Pascarella S, Fattori E, Bossa F, Strong W, Schirch V (1992). "Serine hydroxymethyltransferase: origin of substrate specificity." Biochemistry 31(1);155-62. PMID: 1731867

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

Baggott00: Baggott JE (2000). "Hydrolysis of 5,10-methenyltetrahydrofolate to 5-formyltetrahydrofolate at pH 2.5 to 4.5." Biochemistry 39(47);14647-53. PMID: 11087421

Bartsch08: Bartsch O, Hagemann M, Bauwe H (2008). "Only plant-type (GLYK) glycerate kinases produce d-glycerate 3-phosphate." FEBS Lett 582(20);3025-8. PMID: 18675808

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

Bernstein78: Bernstein LH, Grisham MB, Cole KD, Everse J (1978). "Substrate inhibition of the mitochondrial and cytoplasmic malate dehydrogenases." J Biol Chem 253(24);8697-701. PMID: 214429

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

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

Chandran06: Chandran V, Luisi BF (2006). "Recognition of enolase in the Escherichia coli RNA degradosome." J Mol Biol 358(1):8-15. PMID: 16516921

Chistoserdova03: Chistoserdova L, Chen SW, Lapidus A, Lidstrom ME (2003). "Methylotrophy in Methylobacterium extorquens AM1 from a genomic point of view." J Bacteriol 185(10);2980-7. PMID: 12730156

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: identification of sgaA and mtdA and sequences of sgaA, hprA, and mtdA." J Bacteriol 176(7);1957-68. PMID: 8144463

Chistoserdova94b: 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

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

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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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