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Associate Professor
Tomokazu ITO
Ph. D.（agr）

Lab, of Applied Enzymology,
Graduate School of Bioagricultural Sciences,
Nagoya University
 
略歴

2004. 3                       名古屋大学農学部応用生物科学科　卒業
2009. 3                       名古屋大学大学院生命農学研究科 博士課程　修了[博士(農学)]
2008. 4 - 2009. 3 　   日本学術振興会特別研究員 (DC2) 
2009. 4 - 2010. 3　　京都大学化学研究所 博士研究員 (日本学術振興会特別研究員 (PD)
2010. 4 - 2016. 5        名古屋大学大学院　生命農学研究科　助教
2016. 6 - 2023. 6        名古屋大学大学院　生命農学研究科　講師

2018. 7 - 2019. 7.       米国University of Georgia, visiting scholar

2023. 7 -　　　　　 名古屋大学大学院　生命農学研究科　准教授　現在に至る

​

 Metabolism in living organisms is both dynamically regulated and precisely controlled. Our research focuses on the molecular functions and metabolic control mechanisms of vitamins B6 and B9, as well as amino acids.

 We study enzymes and proteins from microorganisms that are involved in the metabolism of these compounds. By conducting structural and kinetic analyses with purified enzymes and proteins, along with genetic and metabolic analyses using microbial mutants, we try to uncover the molecular basis of the physiological functions and metabolic regulation of vitamins and amino acids.

Research on the regulatory mechanisms govering vitamin B6 homeostasis and the cross-talk between vitamin B6 and amino acid metabolism.

1

　Vitamin B6 is the generic name for the six compounds shown in the figure given Of these, pyridoxal phosphate (PLP) acts as a cofactor for many amino acid metabolising enzymes and is involved in a wide range of biological metabolisms. For this reason, a disturbance in the homeostasis of vitamin B6 has a pronounced effect on the metabolism of living organisms.

We focus on the molecular mechanisms underlying vitamin B6 homeostasis and the crosstalk between changes in vitamin B6 dynamics and metabolism in vivo.

Selected papers

Review that summarizes research on PLPBP, a key factor in vitamin B6 homeostasis.

　Ito T. (2022). Role of the conserved pyridoxal 5'-phosphate-binding protein YggS/PLPBP in vitamin B6 and amino acid homeostasis. Bioscience, biotechnology, and biochemistry, 86(9), 1183–1191.​

​

First identification of the bacterial pyridoxal reductase (PLR, see above figure), which catalyzes the pyridoxal (PL) → pyridoxine (PN) conversion.

　Ito, T., & Downs, D. M. (2020). Pyridoxal reductase, PdxI, is critical for salvage of pyridoxal in Escherichia coli.Journal of bacteriology, 202(12), e00056-20.

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PNP-dependent inhibition of glycine cleavage system as a factor in diverse phenotypes associated with PLPBP deficiency.
​　Ito T, Hori R, Hemmi H, Downs DM, Yoshimura T. (2020) Inhibition of glycine cleavage system by pyridoxine 5'-phosphate causes synthetic lethality in glyA yggS and serA yggS in Escherichia coli.  Molecular Microbiology.  2020 113, 270-284.

2

Studies on the metabolism and functions of D-amino acids 

Most amino acids exist in two forms: L- and D-amino acids. The amino acids that constitute our bodies are predominantly L-amino acids. Historically, D-type amino acids were thought to function mainly in prokaryotes, such as in bacterial cell wall peptidoglycan and antibiotics. However, various D-amino acids have been found in plants, insects, and mammals, revealing their significant physiological roles.

We discovered the first D-serine-specific degrading enzyme in eukaryotes, "D-serine dehydratase," and have been studying its structure-function relationship, physiological roles, and potential applications. Additionally, we have been analyzing various other D-amino acid metabolic enzymes.

Selected papers

Development of a novel in vivo platform for the identification of D-amino acid synthetic enzymes.
　　Ito, T., Muto, N., Sakagami, H., Tanaka, M., Hemmi, H., & Yoshimura, T. (2023). d-amino acid auxotrophic Escherichia coli strain for in vivo functional cloning of novel d-amino acid synthetic enzyme. The FEBS journal, 290(11), 2895–2908. 

Involvement of mammalian serine racemase in D-aspartate biosynthesis
　　Ito, T., Hayashida, M., Kobayashi, S., Muto, N., Hayashi, A., Yoshimura, T., & Mori, H. (2016). Serine racemase is involved in d-aspartate biosynthesis. Journal of biochemistry, 160(6), 345–353. 

Identification of a novel Zn2+-dependent D-serine degrading enzyme, D-serine dehydratase
　　Ito, T., Hemmi, H., Kataoka, K., Mukai, Y., & Yoshimura, T. (2008). A novel zinc-dependent D-serine dehydratase from Saccharomyces cerevisiae. The Biochemical journal, 409(2), 399–406. 

Development of the first D-,L-serine enzyme assay using D-serine dehydratase
　　Ito, T., Takahashi, K., Naka, T., Hemmi, H., & Yoshimura, T. (2007). Enzymatic assay of D-serine using D-serine dehydratase from Saccharomyces cerevisiae. Analytical biochemistry, 371(2), 167–172. 

3

​補酵素の新奇な合成・代謝経路に関する研究
​　代謝変動に際し、遺伝子・タンパク質の量的変動や、翻訳後修飾はよく議論されるが、酵素反応の必須の構成因子である補酵素に関してはほとんど着目されてこなかった。我々がPLPBPの機能解析で明らかとしたように、多様な構造アナログが存在しうるビタミンにおいては、各ビタマーは別個の分子として取り扱う必要がある。本研究では、各ビタマーの構造多様性を再評価し、これらビタマーの動的変動が関わる生体システムを明らかとする研究を進めている。補酵素が「制御因子」として機能することを例証し、これを介した応用展開を目指している。

Publications

  1. A [4Fe-4S] cluster resides at the active center of phosphomevalonate dehydratase, a key enzyme in the archaeal modified mevalonate pathway. (2023) Komeyama, M., Kanno, K., Mino, H., Yasuno, Y., Shinada, T., Ito, T. & Hemmi, H. Frontiers in Microbiology, 14, 1150353. 

  2. D-amino acid auxotrophic Escherichia coli strain for in vivo functional cloning of novel D-amino acid synthetic enzyme. (2023) Ito T, Muto N, Sakagami H, Tanaka M, Hemmi H, Yoshimura T The FEBS journal, 290(11), 2895–2908. 

  3. Role of the conserved pyridoxal 5ʹ-phosphate-binding protein YggS/PLPBP in vitamin B6 and amino acid homeostasis. (2022) Ito T. Bioscience, biotechnology, and biochemistry, 86(9):1183-1191 

  4. Crystal structure of mevalonate 3,5-bisphosphate decarboxylase reveals insight into the evolution of decarboxylases in the mevalonate metabolic pathways. (2022) Aoki, M., Vinokur, J., Motoyama, K., Ishikawa, R., Collazo, M., Cascio, D., Sawaya, M. R., Ito, T., Bowie, J. U., & Hemmi, H. The Journal of biological chemistry, 98(7):102111 

  5. Identification and characterization of a serine racemase in the silkworm Bombyx mori. (2022) Tanaka, Y., Yoshimura, T., Hakamata, M., Saito, C., Sumitani, M., Sezutsu, H., Hemmi, H., & Ito, T. Journal of biochemistry, 172(1), 17–28. 

  6. Identification and biochemical characterization of a heteromeric cis-prenyltransferase from the thermophilic archaeon Archaeoglobus fulgidus. (2022) Sompiyachoke, K., Nagasaka, A., Ito, T., & Hemmi, H. Journal of biochemistry, 171(6), 641–651.

  7. Mechanism of eukaryotic serine racemase-catalyzed serine dehydration. (2020) Ito T, Matsuoka M, Goto M, Watanabe S, Mizobuchi T, Matsushita K, Nasu R, Hemmi H, Yoshimura T.Biochim Biophys Acta Proteins Proteom. May 28:140460. 

  8. Pyridoxal reductase, PdxI, is critical for salvage of pyridoxal in Escherichia coli. (2020) Ito T & Downs DM. Journal of Bacteriology. 202. e00056-20.

  9. Inhibition of glycine cleavage system by pyridoxine 5'-phosphate causes synthetic lethality in glyA yggS and serA yggS in Escherichia coli. (2020)  Ito T, Hori R, Hemmi H, Downs DM, Yoshimura T.  Molecular Microbiology.  2020 113, 270-284. 

  10. Conserved pyridoxal 5'-phosphate binding protein YggS impacts amino acid metabolism through pyridoxine 5'-phosphate in Escherichia coli.  (2019)  Ito, T., Yamamoto, K., Hori, R., Yamauchi, A., Downs, DM., Hemmi, H. & Yoshimura. T. Applied and Environmental Microbiology. 85, e00430-19.

  11. Urinary D-serine level as a predictive biomarker for deterioration of renal function in patients with atherosclerotic risk factors. (2019)  Iwakawa, H., Makabe, S., Ito, T., Yoshimura, T. & Watanabe H. Biomarkers. 24, 159-165. 

  12. Modified mevalonate pathway of the archaeon Aeropyrum pernix proceeds via trans-anhydromevalonate 5-phosphate. (2018) Hayakawa, H., Motoyama, K., Sobue, F., Ito, T., Kawaide, H., Yoshimura, T. & Hemmi, H. Proceedings of the National Academy of Sciences of the United States of America. 115, 10034-10039. 

  13. D-Serine metabolism and its importance in development of Dictyostelium discoideum. (2018)  Ito, T., Hamauchi, N., Hagi, T., Morohashi, N., Hemmi, H., Sato, G. Y., Saito, T. & Yoshimura, T. Frontiers in Microbiology. 9: 784 

  14. Production of ophthalmic acid using engineered Escherichia coli . (2018) Ito T, Tokoro M, Hori R, Hemmi H, Yoshimura T. (2018)  Applied and Environmental Microbiology. 84: e02806-17. 

  15. Utilization of an intermediate of the methylerythritol phosphate pathway, (E)-4-hydroxy-3-methylbut-2-en-1-yl diphosphate, as the prenyl donor substrate for various prenyltransferases. (2018) Hayashi, Y., Ito, T., Yoshimura, T. & Hemmi, H. Bioscience, Biotechnology, and Biochemistry. 82, 993-1002.  

  16. Occurrence of the (2R,3S)-isomer of 2-amino-3,4-dihydroxybutanoic acid in the mushroom Hypsizygus marmoreus. (2017) Ito T, Yu Z., Yoshino I., Hirozawa Y., Yamamoto K., Shinoda K., Watanabe A., Hemmi H., Asada Y., Yoshimura T. J Agric Food Chem. 65. 131-6139

  17. Ophthalmic acid accumulation in an Escherichia coli mutant lacking the conserved pyridoxal 5'-phosphate-binding protein YggS. (2016)  Ito T., Yamauchi A., Hemmi H., Yoshimura T.  Journal of Bioscience and Bioengineering.  122. 689-693

  18. Serine racemase is involved in D-aspartate biosynthesis. (2016) Ito T., Hayashida M., Kobayashi S., Muto N., Hayashi A., Yoshimura T., Mori H. Journal of Biochemistry.　160. 345-353

  19. Development of a versatile method for targeted gene deletion and insertion by using the pyrF gene in the psychrotrophic bacterium, Shewanella livingstonensis Ac10 . (2016) Ito T., Gong C., Kawamoto J., Kurihara T. Journal of Bioscience and Bioengineering. 122.  645-651

  20. mTORC1 is involved in the regulation of branched-chain amino acid (BCAA) catabolism in mouse heart. (2016) Zhen H., Kitaura Y., Kadota Y., Ishikawa T., Kondo Y., Xu M., Morishita Y., Ota M., Ito T., Shimomura Y. FEBS Open Bio. 6. 43-49

  21. Eukaryotic d-Serine Dehydratase.  (2016) Ito, T. Yoshimura, T Ishida, H Tanaka - D-Amino Acids, 2016 - Springer 

  22. A New Member of MocR/GabR-type PLP-Binding Regulator of D-Alanyl-D-Alanine Ligase in Brevibacillus brevis. (2015) Takenaka T., Ito T*., Miyahara I., Hemmi H., Yoshimura T. FEBS J.282. 4201-4217.

  23. Domain characterization of Bacillus subtilis GabR, a pyridoxal  5'-phosphate-dependent transcriptional regulator. (2015) Okuda K., Ito T., Goto M., Takenaka T., Hemmi H., Yoshimura T. Journal of Biochemistry. 158. 225-234 [PubMed] 

  24. PEGylated D-Serine Dehydratase as a D-Serine Reucing Agent. (2015) Ito T., Takada H., Isobe K., Suzuki M., Kitaura Y., Hemmi H., Matsuda T., Sasabe J., Yoshimura T. Journal of Pharmaceutical and Biomedical Analysis. 116. 34-9 [PubMed]

  25. Role of the aminotransferase domain in Bacillus subtilis GabR, a pyridoxal 5'-phosphate-dependent transcriptional regulator. (2015) Okuda K., Kato S., Ito T., Shiraki S., Kawase Y., Goto M., Kawashima S., Hemmi H., Fukada H., Yoshimura T. Molecular Microbiology. 95. 245-257 

  26. Is D-aspartate produced by glutamic-oxaloacetic transaminase-1 like 1 (Got1l1), a putative aspartate racemase? (2015) Tanaka-Hayashi A., Hayashi S., Inoue R., Ito T., Kouno K., Yoshida T., Watanabe M., Yoshimura T., Mori H. Amino Acids. 47. 79-86 

  27. 酵母D-セリンデヒドラターゼの反応機構 (Reaction mechanism of yeast D-serine dehydratase) (2014) 松岡舞, 伊藤智和, 吉村徹. Vitamins. 88 (11) 576-579

  28. ビタミンB6が担うD-セリンの機能と代謝：セリンラセマーゼとD-セリンデヒドラターゼ (Vitami B6-dependet enzymes involved in D-serine metabolism: serine racemase and D-serine dehydratase)  (2014) 吉村徹, 伊藤智和. Vitamins. 88 (9) 462-468

  29. 真核生物型セリンラセマーゼの反応機構 (Reaction mechanism of eukaryotic serine racemase) (2014) 吉村徹, 伊藤智和. Vitamins. 88 (8) 425-428

  30. Reaction mechanism of Zn2+-dependent D-serine dehydratase: role of a conserved tyrosine residue interacting with pyridine ring nitrogen of pyridoxal 5'-phosphate. (2014) Ito T., Matsuoka M., Koga K., Hemmi H., Yoshimura T.Journal of Biochemistry. 156. 173-180 

  31. D-アミノ酸代謝関連酵素--構造・機能研究の最前線--「D－セリンデヒドラターゼ」について執筆担当, BIOINDUSTRY, シーエムシー出版, 2014年3月号

  32. Conserved pyridoxal protein that regulates Ile and Val metabolism. (2013) Ito T., Iimori J., Takayama S., Moriyama A., Yamauchi A., Hemmi H., Yoshimura T. Journal of Bacteriology. 195. 5439-5449 

  33. Catalytic mechanism of serine racemase from Dictyostelium discoideum. (2013) Ito T., Maekawa M., Hyashi S., Goto M., Hemmi H., Yoshimura T. Amino Acids. 44. 1073-84 

  34. Metal ion dependency of serine racemase from Dictyostelium discoideum. (2012) Ito T., Murase H., Maekawa M., Hayashi S., Maki M., Hemmi H., Yoshimura T. Amino Acids. 43. 1567-1576 

  35. Role of zinc ion for catalytic activity in D-serine dehydratase from Saccharomyces cerevisiae. (2012) Ito T., Koga K., Hemmi H., Yoshimura T. FEBS J. 279. 612-624 

  36. 哺乳類のアスパラギン酸ラセマーゼ （Aspartate racemase of mammals)  (2011) 伊藤智和, 吉村徹 Vitamins. 85. 661-662

  37. 右手型アミノ酸の役割　（2010） 伊藤智和 生物工学会誌　88. 613

  38. A highly sensitive enzymatic assay for D- and total serine detection using D-serine dehydratase from Saccharomyces cerevisiae (2010) Naka T., Ito T., Hemmi H., Yoshimura T. Journal of molecular catalysis. B, Enzymatic. 67. 150-154 

  39. The implication of YggT of Escherichia coli in osmotic regulation (2009) Ito T., Uozumi N., Nakamura T., Takayama S., Matsuda N., Aiba H., Hemmi H., Yoshimura T.  Bioscience, Biotechnology, and Biochemistry. 73. 2698-704. [PubMed]

  40. A novel zinc-dependent D-serine dehydratase from Saccharomyces cerevisiae (2008) Ito T., Hemmi H., Kataoka K., Mukai Y., Yoshimura T. Biochemical Journal 409, 399-406. 

  41. Saccharomyces cerevisiaeの新奇D-セリンデヒドラターゼとD-セリン定量への応用 (A novel D-serine dehydratase from Saccharomyces cerevisiae and its application to D-serine assay)  (2008) 伊藤智和, 吉村徹 Vitamins. 82. 349-351

  42. Enzymatic assay of D-serine using D-serine dehydratase from Saccharomyces cerevisiae. (2007) Ito T., Takahashi K., Naka T., Hemmi H., Yoshimura T. Analytical biochemistry. 371. 167-72.

052-789-4120

ito-t(@)agr.nagoya-u.ac.jp

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