Updated BioCyc iOS App now
available in iTunes store
Updated BioCyc iOS App now
available in iTunes store
Updated BioCyc iOS App now
available in iTunes store
Updated BioCyc iOS App now
available in iTunes store
Updated BioCyc iOS App now
available in iTunes store

MetaCyc Pathway: 2-aminoethylphosphonate biosynthesis
Inferred from experimentTraceable author statement to experimental support

Enzyme View:

Pathway diagram: 2-aminoethylphosphonate biosynthesis

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: BiosynthesisSecondary Metabolites Biosynthesis

Some taxa known to possess this pathway include : Tetrahymena pyriformis, Trypanosoma cruzi

Expected Taxonomic Range: Alveolata, Euglenozoa, Opisthokonta

General Background

Phosphonates are compounds that contain a carbon-phosphorus bond which provides chemical and biochemical stability. Phosphonates are synthesized as secondary metabolites by a variety of prokaryotes and lower eukaryotes and are part of the global phosphorus cycle (in [Chen06a, Kulakova09]). phosphoenolpyruvate is the key precursor of phosphonate biosynthesis (in [Bowman88]). Formation of the carbon-phosphorus bond in phosphonates is catalyzed by the key enzyme phosphoenolpyruvate mutase EC, as shown here in the pathway for biosynthesis of (2-aminoethyl)phosphonate. This enzyme also participates in the biosynthesis of other phosphonates, examples of which are shown in pathways fosfomycin biosynthesis, phosphinothricin tripeptide biosynthesis (bialaphos biosynthesis) and dehydrophos biosynthesis.

(2-aminoethyl)phosphonate (ciliatine) is the most common naturally occurring phosphonate. It is synthesized in eukaryotes (fungi [Wassef76], metazoa [Urai09, Araki89, Kariotoglou03], protozoa [Dawson67, Horiguchi72, Barry88, Sarkar03]) where it is a incorporated into cellular lipids, glycolipids and proteins by covalent linkage. However, the physiological role of such phosphonate-containing macromolecules has not yet been determined (in [Sarkar03] and [Kim96]). (2-aminoethyl)phosphonate can be degraded by soil bacteria (see pathways 2-aminoethylphosphonate degradation I and 2-aminoethylphosphonate degradation II).

About This Pathway

This pathway was first described in the free-living, ciliated protozan Tetrahymena pyriformis [Horiguchi72, Barry88]. In the first reaction phosphoenolpyruvate and 3-phosphonopyruvate are reversibly interconverted by a mutase which forms the carbon-phosphorus bond in 3-phosphonopyruvate [Seidel88, Bowman88]. Although the reaction equilibrium strongly favors phosphoenolpyruvate formation, studies have suggested that the phosphomutase and the α-ketodecarboxylase reaction that follows are coupled and phosphoenolpyruvate is shuttled from one active site to the other [Bowman88]. The third reaction represents an amination of phosphonoacetaldehyde as suggested by [Horiguchi72, Barry88].

Created 22-Jul-2011 by Fulcher CA, SRI International


Araki89: Araki S, Abe S, Ando S, Kon K, Fujiwara N, Satake M (1989). "Structure of phosphonoglycosphingolipid containing pyruvylated galactose in nerve fibers of Aplysia kurodai." J Biol Chem 264(33);19922-7. PMID: 2584202

Barry88: Barry RJ, Bowman E, McQueney M, Dunaway-Mariano D (1988). "Elucidation of the 2-aminoethylphosphonate biosynthetic pathway in Tetrahymena pyriformis." Biochem Biophys Res Commun 153(1);177-82. PMID: 3132161

Bowman88: Bowman E, McQueney M, Barry RJ, Dunaway-Mariano D (1988). "Catalysis and thermodynamics of the phosphoenolpyruvate/phosphonopyruvate rearrangement. Entry into the phosphonate class of naturally occurring organophosphorus compounds." J. Am. Chem. Soc. 110, 5575-5576.

Bowman90: Bowman ED, McQueney MS, Scholten JD, Dunaway-Mariano D (1990). "Purification and characterization of the Tetrahymena pyriformis P-C bond forming enzyme phosphoenolpyruvate phosphomutase." Biochemistry 29(30);7059-63. PMID: 2121271

Chen06a: Chen CC, Han Y, Niu W, Kulakova AN, Howard A, Quinn JP, Dunaway-Mariano D, Herzberg O (2006). "Structure and kinetics of phosphonopyruvate hydrolase from Variovorax sp. Pal2: new insight into the divergence of catalysis within the PEP mutase/isocitrate lyase superfamily." Biochemistry 45(38);11491-504. PMID: 16981709

Dawson67: Dawson RM, Kemp P (1967). "The aminoethylphosphonate-containing lipids of rumen protozoa." Biochem J 105(2);837-42. PMID: 4967076

Horiguchi72: Horiguchi M (1972). "Biosynthesis of 2-aminoethylphosphonic acid in cell-free preparations from Tetrahymena." Biochim Biophys Acta 261(1);102-13. PMID: 4622267

Kariotoglou03: Kariotoglou DM, Mastronicolis SK (2003). "Sphingophosphonolipid molecular species from edible mollusks and a jellyfish." Comp Biochem Physiol B Biochem Mol Biol 136(1);27-44. PMID: 12941637

Kim96: Kim J, Dunaway-Mariano D (1996). "Phosphoenolpyruvate mutase catalysis of phosphoryl transfer in phosphoenolpyruvate: kinetics and mechanism of phosphorus-carbon bond formation." Biochemistry 35(14);4628-35. PMID: 8605214

Kulakova09: Kulakova AN, Kulakov LA, Villarreal-Chiu JF, Gilbert JA, McGrath JW, Quinn JP (2009). "Expression of the phosphonoalanine-degradative gene cluster from Variovorax sp. Pal2 is induced by growth on phosphonoalanine and phosphonopyruvate." FEMS Microbiol Lett 292(1);100-6. PMID: 19191873

Sarkar03: Sarkar M, Hamilton CJ, Fairlamb AH (2003). "Properties of phosphoenolpyruvate mutase, the first enzyme in the aminoethylphosphonate biosynthetic pathway in Trypanosoma cruzi." J Biol Chem 278(25);22703-8. PMID: 12672809

Seidel88: Seidel HM, Freeman S, Seto H, Knowles JR (1988). "Phosphonate biosynthesis: isolation of the enzyme responsible for the formation of a carbon-phosphorus bond." Nature 335(6189);457-8. PMID: 3138545

Urai09: Urai M, Nakamura T, Uzawa J, Baba T, Taniguchi K, Seki H, Ushida K (2009). "Structural analysis of O-glycans of mucin from jellyfish (Aurelia aurita) containing 2-aminoethylphosphonate." Carbohydr Res 344(16);2182-7. PMID: 19732869

Wassef76: Wassef MK, Hendrix JW (1976). "Ceramide aminoethylphosphonate in the fungus Pythium prolatum." Biochim Biophys Acta 486(1);172-8. PMID: 1009132

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

Blodgett05: Blodgett JA, Zhang JK, Metcalf WW (2005). "Molecular cloning, sequence analysis, and heterologous expression of the phosphinothricin tripeptide biosynthetic gene cluster from Streptomyces viridochromogenes DSM 40736." Antimicrob Agents Chemother 49(1);230-40. PMID: 15616300

Borisova10: Borisova SA, Circello BT, Zhang JK, van der Donk WA, Metcalf WW (2010). "Biosynthesis of rhizocticins, antifungal phosphonate oligopeptides produced by Bacillus subtilis ATCC6633." Chem Biol 17(1);28-37. PMID: 20142038

Circello10: Circello BT, Eliot AC, Lee JH, van der Donk WA, Metcalf WW (2010). "Molecular cloning and heterologous expression of the dehydrophos biosynthetic gene cluster." Chem Biol 17(4);402-11. PMID: 20416511

Eliot08: Eliot AC, Griffin BM, Thomas PM, Johannes TW, Kelleher NL, Zhao H, Metcalf WW (2008). "Cloning, expression, and biochemical characterization of Streptomyces rubellomurinus genes required for biosynthesis of antimalarial compound FR900098." Chem Biol 15(8);765-70. PMID: 18721747

Hidaka89: Hidaka T, Mori M, Imai S, Hara O, Nagaoka K, Seto H (1989). "Studies on the biosynthesis of bialaphos (SF-1293). 9. Biochemical mechanism of C-P bond formation in bialaphos: discovery of phosphoenolpyruvate phosphomutase which catalyzes the formation of phosphonopyruvate from phosphoenolpyruvate." J Antibiot (Tokyo) 42(3);491-4. PMID: 2708146

Hidaka92a: Hidaka T, Iwakura H, Imai S, Seto H (1992). "Studies on the biosynthesis of fosfomycin. 3. Detection of phosphoenol-pyruvate phosphomutase activity in a fosfomycin high-producing strain of Streptomyces wedmorensis and characterization of its blocked mutant NP-7." J Antibiot (Tokyo) 45(6);1008-10. PMID: 1500341

Hidaka95: Hidaka T, Goda M, Kuzuyama T, Takei N, Hidaka M, Seto H (1995). "Cloning and nucleotide sequence of fosfomycin biosynthetic genes of Streptomyces wedmorensis." Mol Gen Genet 249(3);274-80. PMID: 7500951

Huang99: Huang K, Li Z, Jia Y, Dunaway-Mariano D, Herzberg O (1999). "Helix swapping between two alpha/beta barrels: crystal structure of phosphoenolpyruvate mutase with bound Mg(2+)-oxalate." Structure 7(5);539-48. PMID: 10378273

Jia99: Jia Y, Lu Z, Huang K, Herzberg O, Dunaway-Mariano D (1999). "Insight into the mechanism of phosphoenolpyruvate mutase catalysis derived from site-directed mutagenesis studies of active site residues." Biochemistry 38(43);14165-73. PMID: 10571990

Kim98b: Kim A, Kim J, Martin BM, Dunaway-Mariano D (1998). "Isolation and characterization of the carbon-phosphorus bond-forming enzyme phosphoenolpyruvate mutase from the mollusk Mytilus edulis." J Biol Chem 273(8);4443-8. PMID: 9468496

Latendresse13: Latendresse M. (2013). "Computing Gibbs Free Energy of Compounds and Reactions in MetaCyc."

Liu02b: Liu S, Lu Z, Jia Y, Dunaway-Mariano D, Herzberg O (2002). "Dissociative phosphoryl transfer in PEP mutase catalysis: structure of the enzyme/sulfopyruvate complex and kinetic properties of mutants." Biochemistry 41(32);10270-6. PMID: 12162742

Liu04c: Liu S, Lu Z, Han Y, Jia Y, Howard A, Dunaway-Mariano D, Herzberg O (2004). "Conformational flexibility of PEP mutase." Biochemistry 43(15);4447-53. PMID: 15078090

Schwartz98: Schwartz D, Recktenwald J, Pelzer S, Wohlleben W (1998). "Isolation and characterization of the PEP-phosphomutase and the phosphonopyruvate decarboxylase genes from the phosphinothricin tripeptide producer Streptomyces viridochromogenes Tu494." FEMS Microbiol Lett 163(2);149-57. PMID: 9673017

Seidel90: Seidel HM, Freeman S, Schwalbe CH, Knowles JR (1990). "Phosphonate biosynthesis: the stereochemical course of phosphoenolpyruvate mutase." J. Am. Chem. Soc. 112, 8149-8155.

Seidel92: Seidel HM, Pompliano DL, Knowles JR (1992). "Phosphonate biosynthesis: molecular cloning of the gene for phosphoenolpyruvate mutase from Tetrahymena pyriformis and overexpression of the gene product in Escherichia coli." Biochemistry 31(9);2598-608. PMID: 1547241

Seidel94: Seidel HM, Knowles JR (1994). "Interaction of inhibitors with phosphoenolpyruvate mutase: implications for the reaction mechanism and the nature of the active site." Biochemistry 33(18);5641-6. PMID: 8180189

Woodyer07: Woodyer RD, Li G, Zhao H, van der Donk WA (2007). "New insight into the mechanism of methyl transfer during the biosynthesis of fosfomycin." Chem Commun (Camb) NIL(4);359-61. PMID: 17220970

Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by Pathway Tools version 19.5 (software by SRI International) on Tue May 3, 2016, biocyc14.