Distribution and evolution of the serine/aspartate racemase family in invertebrates
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Free d-amino acids have been found in various invertebrate phyla, while amino acid racemase genes have been identified in few species. The purpose of this study is to elucidate the distribution, function, and evolution of amino acid racemases in invertebrate animals. We searched the GenBank databases, and found 11 homologous serine racemase genes from eight species in eight different invertebrate phyla. The cloned genes were identified based on their maximum activity as Acropora millepora (Cnidaria) serine racemase (SerR) and aspartate racemase (AspR), Caenorhabditis elegans (Nematoda) SerR, Capitella teleta (Annelida) SerR, Crassostrea gigas (Mollusca) SerR and AspR, Dugesia japonica (Platyhelminthes) SerR, Milnesium tardigradum (Tardigrada) SerR, Penaeus monodon (Arthropoda) SerR and AspR and Strongylocentrotus purpuratus (Echinodermata) AspR. We found that Acropora, Aplysia, Capitella, Crassostrea and Penaeus had two amino acid racemase paralogous genes and these paralogous genes have evolved independently by gene duplication at their recent ancestral species. The transcriptome analyses using available SRA data and enzyme kinetic data suggested that these paralogous genes are expressed in different tissues and have different functions in vivo. Phylogenetic analyses clearly indicated that animal SerR and AspR are not separated by their particular racemase functions and form a serine/aspartate racemase family cluster. Our results revealed that SerR and AspR are more widely distributed among invertebrates than previously known. Moreover, we propose that the triple serine loop motif at amino acid positions 150–152 may be responsible for the large aspartate racemase activity and the AspR evolution from SerR.
Keywordsd-Amino acid Serine racemase Aspartate racemase d-Ser d-Asp
Aplysia californica d-amino acid racemase 1
Expressed sequence tag
Glutamic-oxaloacetic transaminase 1-like 1
Reads per kilobase per million reads
Reads per kilobase per million mapped reads
Sequence read archive
Reverse transcription polymerase chain reaction
This work was supported by a Grant-in-Aid for Scientific Research in Japan to KU (24770068 and 15K07152).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
The article does not contain any studies with human participants or animals performed by any of the authors.
- 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(2):235–244. doi: 10.1093/jb/mvj028 CrossRefPubMedGoogle Scholar
- Campbell LI, Rota-Stabelli O, Edgecombe GD, Marchioro T, Longhorn SJ, Telford MJ, Philippe H, Rebecchi L, Peterson KJ, Pisani D (2011) MicroRNAs and phylogenomics resolve the relationships of Tardigrada and suggest that velvet worms are the sister group of Arthropoda. Proc Natl Acad Sci 108(38):15920–15924PubMedCentralCrossRefPubMedGoogle Scholar
- Foltyn VN, Bendikov I, De Miranda J, Panizzutti R, Dumin E, Shleper M, Li P, Toney MD, Kartvelishvily E, Wolosker H (2005) Serine racemase modulates intracellular d-serine levels through an alpha, beta-elimination activity. J Biol Chem 280(3):1754–1763. doi: 10.1074/jbc.M405726200 CrossRefPubMedGoogle Scholar
- Fujitani Y, Horiuchi T, Ito K, Sugimoto M (2007) Serine racemases from barley, Hordeum vulgare L., and other plant species represent a distinct eukaryotic group: gene cloning and recombinant protein characterization. Phytochemistry 68(11):1530–1536. doi: 10.1016/j.phytochem.2007.03.040 CrossRefPubMedGoogle Scholar
- Hashimoto A, Nishikawa T, Oka T, Takahashi K, Hayashi T (1992) Determination of free amino acid enantiomers in rat brain and serum by high-performance liquid chromatography after derivatization with N-tert.-butyloxycarbonyl-l-cysteine and o-phthaldialdehyde. J Chromatogr B Biomed Sci Appl 582(1):41–48CrossRefGoogle Scholar
- Jiraskova-Vanickova J, Ettrich R, Vorlova B, E Hoffman H, Lepsik M, Jansa P, Konvalinka J (2011) Inhibition of human serine racemase, an emerging target for medicinal chemistry. Current Drug Targets 12(7):1037–1055Google Scholar
- 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. doi: 10.1007/s00726-015-1926-0 PubMedGoogle Scholar
- Okuma E, Fujita E, Amano H, Noda H, Abe H (1995) Distribution of free d-amino acids in the tissues of Crustaceans. Fish Sci 61(1):157–160Google Scholar
- 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(10):1967–1983. doi: 10.1128/MCB.06513-11 PubMedCentralCrossRefPubMedGoogle Scholar
- 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(1):79–86. doi: 10.1007/s00726-014-1847-3 PubMedCentralCrossRefPubMedGoogle Scholar
- Yoshikawa N, Ashida W, Hamase K, Abe H (2011) HPLC determination of the distribution of d-amino acids and effects of ecdysis on alanine racemase activity in kuruma prawn Marsupenaeus japonicus. J Chromatogr B Anal Technol Biomed Life Sci 879(29):3283–3288. doi: 10.1016/j.jchromb.2011.04.026 CrossRefGoogle Scholar