MetaCyc Pathway: formaldehyde assimilation III (dihydroxyacetone cycle)

Pathway diagram: formaldehyde assimilation III (dihydroxyacetone cycle)

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

Synonyms: dihydroxyacetone cycle, xylulose-monophosphate cycle

Superclasses: Degradation/Utilization/Assimilation C1 Compounds Utilization and Assimilation Formaldehyde Assimilation

Some taxa known to possess this pathway include ? : Candida boidinii , Candida methanolovescens , Candida methylica , Komagataella pastoris , Ogataea angusta , Ogataea methanolica

Expected Taxonomic Range: Fungi

General Background

Methylotrophs are organisms that are capable of growing on C1 compounds, like methanol. These organisms can derive all their energy and carbon needs from reduced molecules that have no C-C bond. Methylotrophy is found only in a few prokaryotic and eukaryotic microorganisms. While prokaryotic methylotrophs are capable of growing on a variety of C1 compounds (see methane oxidation to methanol I and methanol and methylamine oxidation to formaldehyde), eukaryotic methylotrophs can grow only on methanol.

Methylotrophic eukaryotes include only a few species of yeast that belong to the Pichia and Candida genera. They include Candida boidinii, Candida methanolovescens, Candida methylica, Ogataea angusta (previously known as Hansenula polymorpha), Ogataea methanolica and Komagataella pastoris [Houard02].

In these organisms methanol is oxidized to formaldehyde by the enzyme alcohol oxidase (AOD) in a reaction that produces formaldehyde and hydrogen peroxide (see methanol oxidation to formaldehyde IV). To avoid damage to the cell by these very active compounds, this reaction occurs in peroxisomes, where catalase decomposes the hydrogen peroxide into water and oxygen [vanderKlei06].

The formaldehyde that is formed is a branchpoint, as it can be channeled into either an assimilatory pathway that provides the cells with carbon for biosynthesis (this pathway), or a dissimilatory pathway, which provides the cells with energy (see formaldehyde oxidation II (glutathione-dependent)) [vanderKlei06].

About This Pathway

Methylotrophs usually assimilate carbon by converting three C1 molecules into a single C3 compound via a cyclic pathway, similar to the Calvin-Benson-Bassham cycle used in photosynthesis. In prokaryotes, two such pathways are known, including the ribulose monophosphate cycle (formaldehyde assimilation II (RuMP Cycle)) and the serine pathway (formaldehyde assimilation I (serine pathway)). In methylotrophic yeast only one such pathway exists, the formaldehyde assimilation III (dihydroxyacetone cycle) [vanDijken78].

Three molecules of formaldehyde, generated in the peroxisome by alcohol oxidase, are processed by this pathway into a single molecule of D-glyceraldehyde 3-phosphate, which is shuttled into the core biosynthetic pathways.

The key step of this pathway is the transfer of a glycoaldehyde group from D-xylulose 5-phosphate to formaldehyde, forming dihydroxyacetone and D-glyceraldehyde 3-phosphate. This reaction is catalyzed by dihydroxyacetone synthase (DHAS), another peroxisomal enzyme [Janowicz85]. DHAS). The products of this reaction leave the peroxisome and are rearranged in the cytoplasmic in a pathway that involves many of the enzymes of the pentose phosphate pathway, in a way that regenerates D-xylulose 5-phosphate and, for every three cycles, generates one net molecule of D-glyceraldehyde 3-phosphate that is directed towards biosynthesis [vanDijken78, Anthony82].

Since the diagram does not represent this pathway with clarity, more information is provided here:

For every molecule of D-glyceraldehyde 3-phosphate that is incorporated into biomass, three molecules of formaldehyde are fixed, generating three molecules of dihydroxyacetone, and consuming three molecules of D-xylulose 5-phosphate (X5P). Two of the dihydroxyacetone molecules are condensed with two molecules of D-glyceraldehyde 3-phosphate to produce two molecules of fructose 1,6-bisphosphate, while the third one is converted to D-glyceraldehyde 3-phosphate, 1,3-bisphospho-D-glycerate and finally 3-phospho-D-glycerate, and routed to biosynthesis.

Each of the three molecules of X5P that are utilized is regenerated in a different route. First, the two molecules of fructose 1,6-bisphosphate mention above are dephosphorylated into two molecules of β-D-fructofuranose 6-phosphate by the enzyme EC One molecule of X5P is regenerated directly from β-D-fructofuranose 6-phosphate by EC, in a reaction that also generates a molecule of D-erythrose 4-phosphate. The second X5P molecule is generated from the other β-D-fructofuranose 6-phosphate molecule in a different route, consuming the D-erythrose 4-phosphate and generating D-sedoheptulose 7-phosphate (catalyzed by EC, which is then converted to X5P by EC, in a reaction that also generates D-ribose 5-phosphate. Finally, the D-ribose 5-phosphate molecule is converted to D-ribulose 5-phosphate by EC, which is then converted to the third X5P molecule by EC [Anthony82].

Variants: formaldehyde assimilation I (serine pathway) , formaldehyde assimilation II (RuMP Cycle)

Created 30-Nov-2000 by Pellegrini-Toole A , Marine Biological Laboratory
Revised 16-Apr-2007 by Caspi R , SRI International


Anthony82: Anthony, C. (1982). "The biochemistry of methylotrophs." Academic Press, ISBN10: 012058820X, ISBN13: 9780120588206.

Houard02: Houard S, Heinderyckx M, Bollen A (2002). "Engineering of non-conventional yeasts for efficient synthesis of macromolecules: the methylotrophic genera." Biochimie 84(11);1089-93. PMID: 12595136

Janowicz85: Janowicz ZA, Eckart MR, Drewke C, Roggenkamp RO, Hollenberg CP, Maat J, Ledeboer AM, Visser C, Verrips CT (1985). "Cloning and characterization of the DAS gene encoding the major methanol assimilatory enzyme from the methylotrophic yeast Hansenula polymorpha." Nucleic Acids Res 13(9);3043-62. PMID: 2987872

vanderKlei06: van der Klei IJ, Yurimoto H, Sakai Y, Veenhuis M (2006). "The significance of peroxisomes in methanol metabolism in methylotrophic yeast." Biochim Biophys Acta 1763(12);1453-62. PMID: 17023065

vanDijken78: van Dijken, J.P., Harder, W., Beardsmore, A.J., Quayle, J.R. (1978). "Dihydroxyacetone: an intermediate in the assimilation of methanol by yeasts?." FEMS Microbiology Letters 4: 97-102.

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

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

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.

Babul83: Babul J, Guixe V (1983). "Fructose bisphosphatase from Escherichia coli. Purification and characterization." Arch Biochem Biophys 1983;225(2);944-9. PMID: 6312898

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

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

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

Benov99: Benov L, Fridovich I (1999). "Why superoxide imposes an aromatic amino acid auxotrophy on Escherichia coli. The transketolase connection." J Biol Chem 274(7);4202-6. PMID: 9933617

Berry93: Berry A, Marshall KE (1993). "Identification of zinc-binding ligands in the class II fructose-1,6-bisphosphate aldolase of Escherichia coli." FEBS Lett 318(1);11-6. PMID: 8436219

Berthiaume89: Berthiaume L, Beaudry D, Lazure C, Tolan DR, Sygusch J (1989). "Recombinant anaerobic maize aldolase: overexpression, characterization, and metabolic implications." Arch Biochem Biophys 272(2);281-9. PMID: 2751305

Blom96: Blom NS, Tetreault S, Coulombe R, Sygusch J (1996). "Novel active site in Escherichia coli fructose 1,6-bisphosphate aldolase." Nat Struct Biol 3(10);856-62. PMID: 8836102

Branny98: Branny P, de la Torre F, Garel JR (1998). "An operon encoding three glycolytic enzymes in Lactobacillus delbrueckii subsp. bulgaricus: glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase and triosephosphate isomerase." Microbiology 144 ( Pt 4);905-14. PMID: 9579064

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

Brown09: Brown G, Singer A, Lunin VV, Proudfoot M, Skarina T, Flick R, Kochinyan S, Sanishvili R, Joachimiak A, Edwards AM, Savchenko A, Yakunin AF (2009). "Structural and biochemical characterization of the type II fructose-1,6-bisphosphatase GlpX from Escherichia coli." J Biol Chem 284(6);3784-92. PMID: 19073594

Bystrykh83: Bystrykh LV, Trotsenko IuA (1983). "[Purification and several properties of dihydroxyacetone kinase from the methylotrophic yeast Candida boidinii]." Biokhimiia 48(10);1611-6. PMID: 6315084

Cabezas05: Cabezas A, Costas MJ, Pinto RM, Couto A, Cameselle JC (2005). "Identification of human and rat FAD-AMP lyase (cyclic FMN forming) as ATP-dependent dihydroxyacetone kinases." Biochem Biophys Res Commun 338(4);1682-9. PMID: 16289032

Cancilla95: Cancilla MR, Davidson BE, Hillier AJ, Nguyen NY, Thompson J (1995). "The Lactococcus lactis triosephosphate isomerase gene, tpi, is monocistronic." Microbiology 141 ( Pt 1);229-38. PMID: 7534588

Chaikuad11: Chaikuad A, Shafqat N, Al-Mokhtar R, Cameron G, Clarke AR, Brady RL, Oppermann U, Frayne J, Yue WW (2011). "Structure and kinetic characterization of human sperm-specific glyceraldehyde-3-phosphate dehydrogenase, GAPDS." Biochem J 435(2);401-9. PMID: 21269272

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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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