Advertisement

Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

d-Aspartate oxidase: distribution, functions, properties, and biotechnological applications

Abstract

Recently, substantial levels of acidic d-amino acids, such as d-aspartate and d-glutamate, have been identified in many organisms, from bacteria to mammals, suggesting that acidic d-amino acids have multiple physiological significances. Although acidic d-amino acids found in animals primarily originate from foodstuffs and/or bacteria, the d-aspartate-synthesizing enzyme aspartate racemase is identified in various animals. In eukaryotic organisms, acidic d-amino acids are primarily degraded by the flavoenzyme d-aspartate oxidase (DDO). DDO is found in multiple eukaryotic organisms and may play important roles in acidic d-amino acid utilization, elimination, and intracellular level regulation. Moreover, owing to its perfect enantioselectivity and stereoselectivity, DDO may be a valuable tool in several biotechnological applications, including the identification and quantification of acidic d-amino acids. In this mini-review, previous DDO reports are summarized and the potential bioengineering and biotechnological applications of DDO are discussed.

Key Points

Occurrence and distribution ofd-aspartate oxidase.

・Fundamental properties of d -aspartate oxidase of various eukaryotic organisms.

・Biotechnological applications and potential engineering ofd-aspartate oxidase.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

References

  1. Abe K, Takahashi S, Muroki Y, Kera Y, Yamada RH (2006) Cloning and expression of the pyridoxal 5′-phosphate-dependent aspartate racemase gene from the bivalve mollusk Scapharca broughtonii and characterization of the recombinant enzyme. J Biochem 139:235–244. https://doi.org/10.1093/jb/mvj028

  2. Aliashkevich A, Alvarez L, Cava F (2018) New insights into the mechanisms and biological roles of d-amino acids in complex eco-systems. Front Microbiol 9:683. https://doi.org/10.3389/fmicb.2018.00683

  3. Amery L, Brees C, Baes M, Setoyama C, Miura R, Mannaerts GP, Van Veldhoven PP (1998) C-terminal tripeptide Ser-Asn-Leu (SNL) of human d-aspartate oxidase is a functional peroxisome-targeting signal. Biochem J 336:367–371. https://doi.org/10.1042/bj3360367

  4. Ariyoshi M, Katane M, Hamase K, Miyoshi Y, Nakane M, Hoshino A, Okawa Y, Mita Y, Kaimoto S, Uchihashi M, Fukai K, Ono K, Tateishi S, Hato D, Yamanaka R, Honda S, Fushimura Y, Iwai-Kanai E, Ishihara N, Mita M, Homma H, Matoba S (2017) d-Glutamate is metabolized in the heart mitochondria. Sci Rep 7:43911. https://doi.org/10.1038/srep43911

  5. Burns CL, Main DE, Buckthal DJ, Hamilton GA (1984) Thiazolidine-2-carboxylate derivatives formed from glyoxylate and l-cysteine or l-cysteinylglycine as possible physiological substrates for d-aspartate oxidase. Biochem Biophys Res Commun 125:1039–1045. https://doi.org/10.1016/0006-291x(84)91388-3

  6. Cava F, Lam H, de Pedro MA, Waldor MK (2011) Emerging knowledge of regulatory roles of d-amino acids in bacteria. Cell Mol Life Sci 68:817–831. https://doi.org/10.1007/s00018-010-0571-8

  7. Cristino L, Luongo L, Squillace M, Paolone G, Mango D, Piccinin S, Zianni E, Imperatore R, Iannotta M, Longo F, Errico F, Vescovi AL, Morari M, Maione S, Gardoni F, Nistico R, Usiello A (2015) d-Aspartate oxidase influences glutamatergic system homeostasis in mammalian brain. Neurobiol Aging 36:1890–1902. https://doi.org/10.1016/j.neurobiolaging.2015.02.003

  8. D'Aniello A, Guiditta A (1977) Identification of d-aspartic acid in the brain of Octopus vulgaris Lam. J Neurochem 29:1053–1057. https://doi.org/10.1111/j.1471-4159.1977.tb06508.x

  9. D'Aniello A, Rocca E (1972) d-Aspartate oxidase from the hepatopancreas of Octopus vulgaris Lam. Comp Biochem Physiol B 41:625–633

  10. D'Aniello A, D'Onofrio G, Pischetola M, D'Aniello G, Vetere A, Petrucelli L, Fisher GH (1993) Biological role of d-amino acid oxidase and d-aspartate oxidase. Effects of d-amino acids. J Biol Chem 268:26941–26949

  11. Di Giovanni M, Burrone L, Chieffi Baccari G, Topo E, Santillo A (2010) Distribution of free d-aspartic acid and d-aspartate oxidase in frog Rana esculenta tissues. J Exp Zool A Ecol Genet Physiol 313:137–143. https://doi.org/10.1002/jez.585

  12. Du K, Sun J, Song X, Song C, Feng W (2015) Enhancement of the solubility and stability of d-amino acid oxidase by fusion to an elastin like polypeptide. J Biotechnol 212:50–55. https://doi.org/10.1016/j.jbiotec.2015.07.016

  13. Errico F, Pirro MT, Affuso A, Spinelli P, De Felice M, D'Aniello A, Di Lauro R (2006) A physiological mechanism to regulate d-aspartic acid and NMDA levels in mammals revealed by d-aspartate oxidase deficient mice. Gene 374:50–57. https://doi.org/10.1016/j.gene.2006.01.010

  14. Errico F, Napolitano F, Nistico R, Usiello A (2012) New insights on the role of free d-aspartate in the mammalian brain. Amino Acids 43:1861–1871. https://doi.org/10.1007/s00726-012-1356-1

  15. Errico F, D'Argenio V, Sforazzini F, Iasevoli F, Squillace M, Guerri G, Napolitano F, Angrisano T, Di Maio A, Keller S, Vitucci D, Galbusera A, Chiariotti L, Bertolino A, de Bartolomeis A, Salvatore F, Gozzi A, Usiello A (2015a) A role for d-aspartate oxidase in schizophrenia and in schizophrenia-related symptoms induced by phencyclidine in mice. Transl Psychiatry 5:e512. https://doi.org/10.1038/tp.2015.2

  16. Errico F, Mothet JP, Usiello A (2015b) d-Aspartate: an endogenous NMDA receptor agonist enriched in the developing brain with potential involvement in schizophrenia. J Pharm Biomed Anal 116:7–17. https://doi.org/10.1016/j.jpba.2015.03.024

  17. Fotheringham I, Archer I, Carr R, Speight R, Turner NJ (2006) Preparative deracemization of unnatural amino acids. Biochem Soc Trans 34:287–290. https://doi.org/10.1042/BST20060287

  18. Friedman M (2010) Origin, microbiology, nutrition, and pharmacology of d-amino acids. Chem Biodivers 7:1491–1530. https://doi.org/10.1002/cbdv.200900225

  19. Friedman M, Levin CE (2012) Nutritional and medicinal aspects of d-amino acids. Amino Acids 42:1553–1582. https://doi.org/10.1007/s00726-011-0915-1

  20. Fukunaga S, Yuno S, Takahashi M, Taguchi S, Kera Y, Odani S, Yamada RH (1998) Purification and properties of d-glutamate oxidase from Candida boidinii 2201. J Ferment Bioeng 85:579–583. https://doi.org/10.1016/S0922-338x(98)80008-1

  21. Genchi G (2017) An overview on d-amino acids. Amino Acids 49:1521–1533. https://doi.org/10.1007/s00726-017-2459-5

  22. Han H, Miyoshi Y, Koga R, Mita M, Konno R, Hamase K (2015) Changes in d-aspartic acid and d-glutamic acid levels in the tissues and physiological fluids of mice with various d-aspartate oxidase activities. J Pharm Biomed Anal 116:47–52. https://doi.org/10.1016/j.jpba.2015.05.013

  23. Hashimoto A, Kumashiro S, Nishikawa T, Oka T, Takahashi K, Mito T, Takashima S, Doi N, Mizutani Y, Yamazaki T, Kaneko T, Ootomo E (1993) Embryonic development and postnatal changes in free d-aspartate and d-serine in the human prefrontal cortex. J Neurochem 61:348–351. https://doi.org/10.1111/j.1471-4159.1993.tb03575.x

  24. Huang Y, Shi M, Zhao S (2009) Quantification of d-asp and d-Glu in rat brain and human cerebrospinal fluid by microchip electrophoresis. J Sep Sci 32:3001–3006. https://doi.org/10.1002/jssc.200900026

  25. Ju S-S, Lin L-L, Chien HR, Hsu W-H (2000) Substitution of the critical methionine residues in Trigonopsis variabilisd-amino acid oxidase with leucine enhances its resistance to hydrogen peroxide. FEMS Microbiol Lett 186:215–219. https://doi.org/10.1111/j.1574-6968.2000.tb09107.x

  26. Katane M, Homma H (2010) d-Aspartate oxidase: the sole catabolic enzyme acting on free d-aspartate in mammals. Chem Biodivers 7:1435–1449. https://doi.org/10.1002/cbdv.200900250

  27. Katane M, Homma H (2011) d-Aspartate--an important bioactive substance in mammals: a review from an analytical and biological point of view. J Chromatogr B Anal Technol Biomed Life Sci 879:3108–3121. https://doi.org/10.1016/j.jchromb.2011.03.062

  28. Katane M, Furuchi T, Sekine M, Homma H (2007a) Molecular cloning of a cDNA encoding mouse d-aspartate oxidase and functional characterization of its recombinant proteins by site-directed mutagenesis. Amino Acids 32:69–78

  29. Katane M, Seida Y, Sekine M, Furuchi T, Homma H (2007b) Caenorhabditis elegans has two genes encoding functional d-aspartate oxidases. FEBS J 274:137–149. https://doi.org/10.1111/j.1742-4658.2006.05571.x

  30. Katane M, Hanai T, Furuchi T, Sekine M, Homma H (2008) Hyperactive mutants of mouse d-aspartate oxidase: mutagenesis of the active site residue serine 308. Amino Acids 35:75–82. https://doi.org/10.1007/s00726-007-0627-8

  31. Katane M, Saitoh Y, Seida Y, Sekine M, Furuchi T, Homma H (2010) Comparative characterization of three d-aspartate oxidases and one d-amino acid oxidase from Caenorhabditis elegans. Chem Biodivers 7:1424–1434. https://doi.org/10.1002/cbdv.200900294

  32. Katane M, Saitoh Y, Maeda K, Hanai T, Sekine M, Furuchi T, Homma H (2011) Role of the active site residues arginine-216 and arginine-237 in the substrate specificity of mammalian d-aspartate oxidase. Amino Acids 40:467–476. https://doi.org/10.1007/s00726-010-0658-4

  33. Katane M, Kawata T, Nakayama K, Saitoh Y, Kaneko Y, Matsuda S, Saitoh Y, Miyamoto T, Sekine M, Homma H (2015) Characterization of the enzymatic and structural properties of human d-aspartate oxidase and comparison with those of the rat and mouse enzymes. Biol Pharm Bull 38:298–305. https://doi.org/10.1248/bpb.b14-00690

  34. Katane M, Kanazawa R, Kobayashi R, Oishi M, Nakayama K, Saitoh Y, Miyamoto T, Sekine M, Homma H (2017) Structure-function relationships in human d-aspartate oxidase: characterisation of variants corresponding to known single nucleotide polymorphisms. Biochim Biophys Acta 1865:1129–1140. https://doi.org/10.1016/j.bbapap.2017.06.010

  35. Katane M, Kuwabara H, Nakayama K, Saitoh Y, Miyamoto T, Sekine M, Homma H (2018) Rat d-aspartate oxidase is more similar to the human enzyme than the mouse enzyme. Biochim Biophys Acta 1866:806–812. https://doi.org/10.1016/j.bbapap.2017.12.009

  36. Kato S, Ikuta T, Hemmi H, Takahashi S, Kera Y, Yoshimura T (2012) Enzymatic assay for d-aspartic acid using d-aspartate oxidase and oxaloacetate decarboxylase. Biosci Biotechnol Biochem 76:2150–2152. https://doi.org/10.1271/bbb.120477

  37. Kera Y (1995) Presence of free d-glutamate and d-aspartate in rat tissues. Biochim Biophys Acta 1243:282–286. https://doi.org/10.1016/0304-4165(94)00152-n

  38. Kera Y, Nagasaki H, Iwashima A, Yamada R (1992) Presence of d-aspartate oxidase and free d-aspartate in amphibian (Xenopus laevis, Cynops pyrrhogaster) tissues. Comp Biochem Physiol B 103:345–348

  39. Kera Y, Nagasaki H, Iwashima A, Yamada R (1993) Gender dependence of d-aspartate oxidase activity in rat tissues. Comp Biochem Physiol B 104:739–742

  40. Kera Y, Aoyama H, Watanabe N, Yamada RH (1996) Distribution of d-aspartate oxidase and free d-glutamate and d-aspartate in chicken and pigeon tissues. Comp Biochem Physiol B Biochem Mol Biol 115:121–126

  41. Kera Y, Niino A, Ikeda T, Okada H, Yamada R (1998) Peroxisomal localization of d-aspartate oxidase and development of peroxisomes in the yeast Cryptococcus humicolus UJ1 grown on d-aspartate. Biochim Biophys Acta 1379:399–405. https://doi.org/10.1016/s0304-4165(97)00113-x

  42. Khang Y-H, Kim I-W, Hah Y-R, Hwangbo J-H, Kang K-K (2003) Fusion protein of Vitreoscilla hemoglobin with d-amino acid oxidase enhances activity and stability of biocatalyst in the bioconversion process of cephalosporin C. Biotechnol Bioeng 82:480–488. https://doi.org/10.1002/bit.10592

  43. Kim PM, Duan X, Huang AS, Liu CY, Ming GL, Song H, Snyder SH (2010) Aspartate racemase, generating neuronal d-aspartate, regulates adult neurogenesis. Proc Natl Acad Sci U S A 107:3175–3179. https://doi.org/10.1073/pnas.0914706107

  44. Kolodkin-Gal I, Romero D, Cao S, Clardy J, Kolter R, Losick R (2010) d-Amino acids trigger biofilm disassembly. Science 328:627–629. https://doi.org/10.1126/science.1188628

  45. Lam H, Oh DC, Cava F, Takacs CN, Clardy J, de Pedro MA, Waldor MK (2009) d-Amino acids govern stationary phase cell wall remodeling in bacteria. Science 325:1552–1555. https://doi.org/10.1126/science.1178123

  46. Marcone GL, Rosini E, Crespi E, Pollegioni L (2020) d-Amino acids in foods. Appl Microbiol Biotechnol 104:555–574. https://doi.org/10.1007/s00253-019-10264-9

  47. Matsuda S, Katane M, Maeda K, Kaneko Y, Saitoh Y, Miyamoto T, Sekine M, Homma H (2015) Biosynthesis of d-aspartate in mammals: the rat and human homologs of mouse aspartate racemase are not responsible for the biosynthesis of d-aspartate. Amino Acids 47:975–985. https://doi.org/10.1007/s00726-015-1926-0

  48. Miyoshi Y, Oyama T, Itoh Y, Hamase K (2014) Enantioselective two-dimensional high-performance liquid chromatographic determination of amino acids; analysis and physiological significance of d-amino acids in mammals. Chromatography 35:49–57. https://doi.org/10.15583/jpchrom.2014.005

  49. Mizushima S, Izaki K, Takahashi H, Sakaguchi K-i (1956) Studies on the metabolism of d-amino acid in microorganisms. Bull Agr Chem Soc Japan 20:36–41. https://doi.org/10.1080/03758397.1956.10857301

  50. Molla G, Chaves-Sanjuan A, Savinelli A, Nardini M, Pollegioni L (2019) Structure and kinetic properties of human d-aspartate oxidase, the enzyme-controlling d-aspartate levels in brain. FASEB J 00:1–16. https://doi.org/10.1096/fj.201901703r

  51. Mörtl M, Diederichs K, Welte W, Molla G, Motteran L, Andriolo G, Pilone MS, Pollegioni L (2004) Structure-function correlation in glycine oxidase from Bacillus subtilis. J Biol Chem 279:29718–29727. https://doi.org/10.1074/jbc.M401224200

  52. Mutaguchi Y, Ohmori T, Sakuraba H, Yoneda K, Doi K, Ohshima T (2011) Visible wavelength spectrophotometric assays of l-aspartate and d-aspartate using hyperthermophilic enzyme systems. Anal Biochem 409:1–6. https://doi.org/10.1016/j.ab.2010.10.016

  53. Nagasaki H (1994) Gender-related differences of mouse liver d-aspartate oxidase in the activity and response to administration of d-aspartate and peroxisome proliferators. Int J BioChemiPhysics 26:415–423

  54. Nahalka J, Nidetzky B (2007) Fusion to a pull-down domain: a novel approach of producing Trigonopsis variabilisd-amino acid oxidase as insoluble enzyme aggregates. Biotechnol Bioeng 97:454–461. https://doi.org/10.1002/bit.21244

  55. Negri A, Ceciliani F, Tedeschi G, Simonic T, Ronchi S (1992) The primary structure of the flavoprotein d-aspartate oxidase from beef kidney. J Biol Chem 267:11865–11871

  56. Negri A, Tedeschi G, Ceciliani F, Ronchi S (1999) Purification of beef kidney d-aspartate oxidase overexpressed in Escherichia coli and characterization of its redox potentials and oxidative activity towards agonists and antagonists of excitatory amino acid receptors. Biochim Biophys Acta 1431:212–222. https://doi.org/10.1016/s0167-4838(99)00027-8

  57. Neidle A, Dunlop DS (1990) Developmental changes in free d-aspartic acid in the chicken embryo and in the neonatal rat. Life Sci 46:1517–1522. https://doi.org/10.1016/0024-3205(90)90424-p

  58. Nuzzo T, Feligioni M, Cristino L, Pagano I, Marcelli S, Iannuzzi F, Imperatore R, D'Angelo L, Petrella C, Carella M, Pollegioni L, Sacchi S, Punzo D, De Girolamo P, Errico F, Canu N, Usiello A (2019) Free d-aspartate triggers NMDA receptor-dependent cell death in primary cortical neurons and perturbs JNK activation, Tau phosphorylation, and protein SUMOylation in the cerebral cortex of mice lacking d-aspartate oxidase activity. Exp Neurol 317:51–65. https://doi.org/10.1016/j.expneurol.2019.02.014

  59. Pätzold R, Brückner H (2006) Gas chromatographic determination and mechanism of formation of d-amino acids occurring in fermented and roasted cocoa beans, cocoa powder, chocolate and cocoa shell. Amino Acids 31:63–72. https://doi.org/10.1007/s00726-006-0330-1

  60. Pollegioni L, Molla G (2011) New biotech applications from evolved d-amino acid oxidases. Trends Biotechnol 29:276–283. https://doi.org/10.1016/j.tibtech.2011.01.010

  61. Pollegioni L, Piubelli L, Sacchi S, Pilone MS, Molla G (2007) Physiological functions of d-amino acid oxidases: from yeast to humans. Cell Mol Life Sci 64:1373–1394. https://doi.org/10.1007/s00018-007-6558-4

  62. Punzo D, Errico F, Cristino L, Sacchi S, Keller S, Belardo C, Luongo L, Nuzzo T, Imperatore R, Florio E, De Novellis V, Affinito O, Migliarini S, Maddaloni G, Sisalli MJ, Pasqualetti M, Pollegioni L, Maione S, Chiariotti L, Usiello A (2016) Age-related changes in d-aspartate oxidase promoter methylation control extracellular d-aspartate levels and prevent precocious cell death during brain aging. J Neurosci 36:3064–3078. https://doi.org/10.1523/JNEUROSCI.3881-15.2016

  63. Raj D, Langford M, Krueger S, Shelton M, Welbourne T (2001) Regulatory responses to an oral d-glutamate load: formation of d-pyrrolidone carboxylic acid in humans. Am J Physiol Endocrinol Metab 280:E214–E220. https://doi.org/10.1152/ajpendo.2001.280.2.E214

  64. Rinaldi A, Pellegrini M, Crifo C, De Marco C (1981) Oxidation of meso-diaminosuccinic acid, a possible natural substrate for d-aspartate oxidase. Eur J Biochem 117:635–638. https://doi.org/10.1111/j.1432-1033.1981.tb06385.x

  65. Rosini E, Molla G, Rossetti C, Pilone MS, Pollegioni L, Sacchi S (2008) A biosensor for all d-amino acids using evolved d-amino acid oxidase. J Biotechnol 135:377–384. https://doi.org/10.1016/j.jbiotec.2008.06.001

  66. Rosini E, Molla G, Ghisla S, Pollegioni L (2011) On the reaction of d-amino acid oxidase with dioxygen: O2 diffusion pathways and enhancement of reactivity. FEBS J 278:482–492. https://doi.org/10.1111/j.1742-4658.2010.07969.x

  67. Sacchi S, Lorenzi S, Molla G, Pilone MS, Rossetti C, Pollegioni L (2002) Engineering the substrate specificity of d-amino-acid oxidase. J Biol Chem 277:27510–27516. https://doi.org/10.1074/jbc.M203946200

  68. Saitoh Y, Katane M, Kawata T, Maeda K, Sekine M, Furuchi T, Kobuna H, Sakamoto T, Inoue T, Arai H, Nakagawa Y, Homma H (2012) Spatiotemporal localization of d-amino acid oxidase and d-aspartate oxidases during development in Caenorhabditis elegans. Mol Cell Biol 32:1967–1983. https://doi.org/10.1128/MCB.06513-11

  69. Saitoh Y, Katane M, Miyamoto T, Sekine M, Sakamoto T, Imai H, Homma H (2019) Secreted d-aspartate oxidase functions in C. elegans reproduction and development. FEBS J 286:124–138. https://doi.org/10.1111/febs.14691

  70. Sarower MG, Matsui T, Abe H (2003) Distribution and characteristics of d-amino acid and d-aspartate oxidases in fish tissues. J Exp Zool A Comp Exp Biol 295:151–159. https://doi.org/10.1002/jez.a.10217

  71. Sarower MG, Matsui T, Abe H (2004) Distribution and substrate specificity of d-amino acid and d-aspartate oxidases in marine invertebrates. Sci Asia 30:335–340

  72. Schell MJ, Cooper OB, Snyder SH (1997) d-Aspartate localizations imply neuronal and neuroendocrine roles. Proc Natl Acad Sci U S A 94:2013–2018. https://doi.org/10.1073/pnas.94.5.2013

  73. Setoyama C, Miura R (1997) Structural and functional characterization of the human brain d-aspartate oxidase. J Biochem 121:798–803. https://doi.org/10.1093/oxfordjournals.jbchem.a021655

  74. Simonic T, Duga S, Negri A, Tedeschi G, Malcovati M, Tenchini ML, Ronchi S (1997) cDNA cloning and expression of the flavoprotein d-aspartate oxidase from bovine kidney cortex. Biochem J 322:729–735. https://doi.org/10.1042/bj3220729

  75. Solinas SP, Santoro L, Antonucci A, Cavallini D (1986) The oxidation of cyclothionine by d-aspartate oxidase. Physiol Chem Phys Med NMR 18:71–74

  76. Still JL, Buell MV (1949) Studies on the cyclophorase system; d-aspartic oxidase. J Biol Chem 179:831–837

  77. Stocker A, Hecht H-J, Buckmann AF (1996) Synthesis, characterization and preliminary crystallographic data of N6-(6-carbamoylhexyl)-FAD-d-amino-acid oxidase from pig kidney, a semi-synthetic oxidase. 238:519-528. doi:https://doi.org/10.1111/j.1432-1033.1996.0519z.x

  78. Takahashi S, Takahashi T, Kera Y, Matsunaga R, Shibuya H, Yamada RH (2004) Cloning and expression in Escherichia coli of the d-aspartate oxidase gene from the yeast Cryptococcus humicola and characterization of the recombinant enzyme. J Biochem 135:533–540

  79. Takahashi S, Kakuichi T, Fujii K, Kera Y, Yamada RH (2005) Physiological role of d-aspartate oxidase in the assimilation and detoxification of d-aspartate in the yeast Cryptococcus humicola. Yeast 22:1203–1212. https://doi.org/10.1002/yea.1303

  80. Takahashi S, Shimada K, Nozawa S, Goto M, Abe K, Kera Y (2016) Possible role of a histidine residue in the substrate specificity of yeast d-aspartate oxidase. J Biochem 159:371–378. https://doi.org/10.1093/jb/mvv108

  81. Takahashi S, Osugi K, Shimekake Y, Shinbo A, Abe K, Kera Y (2019) Characterization and improvement of substrate-binding affinity of d-aspartate oxidase of the thermophilic fungus Thermomyces dupontii. Appl Microbiol Biotechnol 103:4053–4064. https://doi.org/10.1007/s00253-019-09787-y

  82. Tanaka-Hayashi A, Hayashi S, Inoue R, Ito T, Konno K, Yoshida T, Watanabe M, Yoshimura T, Mori H (2015) Is d-aspartate produced by glutamic-oxaloacetic transaminase-1 like 1 (Got1l1): a putative aspartate racemase? Amino Acids 47:79–86. https://doi.org/10.1007/s00726-014-1847-3

  83. Tedeschi G, Negri A, Ceciliani F, Ronchi S, Vetere A, D'Aniello G, D'Aniello A (1994) Properties of the flavoenzyme d-aspartate oxidase from Octopus vulgaris. Biochim Biophys Acta 1207:217–222. https://doi.org/10.1016/0167-4838(94)00071-9

  84. Tedeschi G, Negri A, Bernardini G, Oungre E, Ceciliani F, Ronchi S (1999) d-Aspartate oxidase is present in ovaries, eggs and embryos but not in testis of Xenopus laevis. Comp Biochem Physiol B Biochem Mol Biol 124:489–494

  85. Uda K, Abe K, Dehara Y, Mizobata K, Sogawa N, Akagi Y, Saigan M, Radkov AD, Moe LA (2016) Distribution and evolution of the serine/aspartate racemase family in invertebrates. Amino Acids 48:387–402. https://doi.org/10.1007/s00726-015-2092-0

  86. Umhau S, Pollegioni L, Molla G, Diederichs K, Welte W, Pilone MS, Ghisla S (2000) The x-ray structure of d-amino acid oxidase at very high resolution identifies the chemical mechanism of flavin-dependent substrate dehydrogenation. Proc Natl Acad Sci U S A 97:12463–12468. https://doi.org/10.1073/pnas.97.23.12463

  87. Van Veldhoven PP, Brees C, Mannaerts GP (1991) d-Aspartate oxidase, a peroxisomal enzyme in liver of rat and man. Biochim Biophys Acta 1073:203–208. https://doi.org/10.1016/0304-4165(91)90203-s

  88. Wakayama M, Nakashima S, Sakai K, Moriguchi M (1994) Isolation, enzyme production and characterization of d-aspartate oxidase from Fusarium sacchari var. elongatum Y-105. J Ferment Bioeng 78:377–379. https://doi.org/10.1016/0922-338x(94)90284-4

  89. Wakayama M, Takashima K, Tau Y, Nakashima S, Sakai K, Moriguchi M (1997) Spectrophotometric assay of d-aspartate and d-glutamate using d-aspartate oxidase with malate dehydrogenase and glutamate dehydrogenase. Anal Biochem 250:252–253. https://doi.org/10.1006/abio.1997.2230

  90. Wang S-J, Yu C-Y, Lee C-K, Chern M-K, Kuan IC (2008) Subunit fusion of two yeast d-amino acid oxidases enhances their thermostability and resistance to H2O2. Biotechnol Lett 30:1415–1422. https://doi.org/10.1007/s10529-008-9694-5

  91. Wierenga RK, Terpstra P, Hol WG (1986) Prediction of the occurrence of the ADP-binding beta alpha beta-fold in proteins, using an amino acid sequence fingerprint. J Mol Biol 187:101–107. https://doi.org/10.1016/0022-2836(86)90409-2

  92. Wilson WE, Koeppe RE (1961) The metabolism of d- and l-glutamic acid in the rat. J Biol Chem 236:365–369

  93. Yamada RH, Nagasaki H, Nagata Y, Wakabayashi Y, Iwashima A (1989) Administration of d-aspartate increases d-aspartate oxidase activity in mouse liver. Biochim Biophys Acta 990:325–328. https://doi.org/10.1016/s0304-4165(89)80053-4

  94. Yamada RH, Ujiie H, Kera Y, Nakase T, Kitagawa K, Imasaka T, Arimoto K, Takahashi M, Matsumura Y (1996) Purification and properties of d-aspartate oxidase from Cryptococcus humicolus UJ1. Biochim Biophys Acta 1294:153–158. https://doi.org/10.1016/0167-4838(96)00012-x

  95. Yamada RH, Kera Y, Toi H, Hayashi T, Arimoto K, Takahashi M, Iwazaki I, Yamashita S (2001) Microbial oxidases of acidic d-amino acids. J Mol Catal B Enzym 12:93–104. https://doi.org/10.1016/s1381-1177(00)00208-3

  96. Yamamoto A, Tanaka H, Ishida T, Horiike K (2010) d-Aspartate oxidase localisation in pituitary and pineal glands of the female pig. J Neuroendocrinol 22:1165–1172. https://doi.org/10.1111/j.1365-2826.2010.02066.x

  97. Zaar K, Volkl A, Fahimi HD (1989) d-Aspartate oxidase in rat, bovine and sheep kidney cortex is localized in peroxisomes. Biochem J 261:233–238. https://doi.org/10.1042/bj2610233

Download references

Acknowledgments

We thank Molla G. and Pollegioni L. at Università degli studi dell’Insubria for providing the image of the crystal structure of human DDO.

Funding

This study was supported by the Grant-in-Aid for Scientific Research (C) (19K05765) to S. Takahashi from the Japan Society for the Promotion of Science.

Author information

ST wrote the manuscript.

Correspondence to Shouji Takahashi.

Ethics declarations

Conflict of interest

The author declares that he has no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Takahashi, S. d-Aspartate oxidase: distribution, functions, properties, and biotechnological applications. Appl Microbiol Biotechnol (2020). https://doi.org/10.1007/s00253-020-10439-9

Download citation

Keywords

  • d-aspartate oxidase
  • Acidic d-amino acids
  • Flavoenzyme
  • Oxidoreductase
  • Applications