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       Appl Environ Microbiol ​(2024) 90:e01106-24.

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​　古細菌型メバロン酸経路が真正細菌にも存在することを初めて見出した論文です。環境メタゲノムからゲノムが再構成された未培養真正細菌での発見になりますが、同菌が、高度好塩性古細菌型メバロン酸経路という別の変形メバロン酸経路や、非メバロン酸経路（メチルエリスリトールリン酸経路）を持つ菌が含まれるクロロフレクサス門に属しているのが大変興味深い点です。なぜこのグループの真正細菌が多様なイソプレノイド前駆体生合成経路を有しているのか、酵素や代謝経路の進化と併せて考えていく必要がありそうです。

       Front Microbiol​(2023)14:1150353.

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​　古細菌型メバロン酸経路は我々が見出した変形代謝経路であり、複数のバリエーションが存在するメバロン酸経路の祖先型だと考えられること、ATP消費が他のメバロン酸経路よりも少なく代謝工学的な利用が期待されることなどから注目を受けています。この論文では、同経路の鍵酵素であるホスホメバロン酸脱水酵素の詳細な酵素学的性質を世界で初めて明らかにしています。特にEPRという手法による分析で、4Fe-4S型の鉄硫黄クラスターの存在を証明したことがポイントです。

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       FEBS J (2023) Jun;290(11):2895-2908.

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　Identifying novel D‑amino acid biosynthetic enzymes is an important step toward understanding the physiological roles of D‑amino acids. However, no in vivo cloning system for D‑amino acid–producing enzymes other than those for D‑alanine and D‑glutamate has been reported to date. In this paper, we describe the development of a new platform that enables in vivo cloning of a wide variety of D‑amino acid–producing enzymes.

FEBS J. (2026) https://doi.org/10.1111/febs.70471

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Pyridoxal 5′-phosphate (PLP), the active form of vitamin B6, is an essential molecule that supports numerous biochemical reactions. In this study, we reveal that a group of enzymes known as AKR1Cs contributes to mammalian vitamin B6 metabolism in a previously unrecognized manner. AKR1Cs convert pyridoxal (PL) into either pyridoxine (PN) or 4‑pyridoxolactone (4PLA). Our findings suggest that AKR1Cs may function as novel regulatory hubs controlling vitamin B6 homeostasis.

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2020~present

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  1. Kito N, Kitaura Y, Iino K, Toriumi K, Noh H, Ogawa N, Arai M, Hemmi H, Ito T. (2026), A new branch of mammalian vitamin B6 metabolism: AKR1C-mediated conversion of pyridoxal to pyridoxine and 4-pyridoxolactone. FEBS J.  25 February 2026 https://doi.org/10.1111/febs.70471​

  2. Ishikawa R, Matsushima N, Ishimine S, Nakamoto H, Hayakawa H, Yasuno Y, Shinada T, Kawaide H, Ito T, Hemmi H. Deciphering the properties and reaction mechanism of anhydromevalonate phosphate decarboxylase, a prenylated flavin mononucleotide-dependent enzyme in the archaeal mevalonate pathway. FEBS J. 2026 Jan 17. doi: 10.1111/febs.70412.​

  3. Takahashi T, SaitoT, Dohgami I, Ito T, Hemmi H. Enhanced isoprenoid production in Escherichia coli cells harboring the archaeal mevalonate pathway. Biochem Biophys Rep, 2025, 44:102307​

  4. Hata A, Ito T, Mori H, Ogawa T, Kurihara T, Hemmi H, Yoshimura

  5.  T. Suicide substrate reaction-like modification of mouse serine racemase with L-serine. J Biochem. 2025, 177(6):437-445.​​

  6. Aoki K, Mutaguchi Y, Hemmi H, Yoshimura T,  Ito T. Identification and characterization of a novel D-branched-chain amino acids importer from Lactobacillus fermentum. ChemBioChem 2025, e202401075 

  7. ​Matsuo H, Yamada N, Hemmi H, Ito T. Identification of YigL as a PLP/PNP phosphatase in Escherichia coli. Appl Environ Microbiol. 2024;90(9):e0127024. doi:10.1128/aem.01270-24

  8. Kanno K, Kuriki R, Yasuno Y, Shinada T, Ito T, Hemmi H. (2024) Archaeal mevalonate pathway in the uncultured bacterium Candidatus Promineifilum breve belonging to the phylum Chloroflexota. Appl Environ Microbiol. Published online July 31, 2024. doi:10.1128/aem.01106-24

  9. Yoshida, R., Motoyama, K., Ito, T., & Hemmi, H. (2024). Effects of producing high levels of hyperthermophile-specific C25,C25-archaeal membrane lipids in Escherichia coli. Biochemical and biophysical research communications, 729, 150349. 

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

  11. 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 J. 290(11):2895-2908.  

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

  13. Yoshimura T. (2022). Molecular basis and functional development of enzymes related to amino acid metabolism. Bioscience, biotechnology, and biochemistry, 86(9):1161-1172 . 

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

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

  16. Abe, T., Hakamata, M., Nishiyama, A., Tateishi, Y., Matsumoto, S., Hemmi, H., Ueda, D., & Sato, T. (2022). Identification and functional analysis of a new type of Z,E-mixed prenyl reductase from mycobacteria. The FEBS journal, 10.1111/febs.16412. 

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

  18. Ashida, H., Murakami, K., Inagaki, K., Sawa, Y., Hemmi, H., Iwasaki, Y., & Yoshimura, T. (2022). Evolution and properties of alanine racemase from Synechocystis sp. PCC6803. Journal of biochemistry, 171(4), 421–428. 

  19. Ito, T., Ogawa, H., Hemmi, H., Downs, D. M., & Yoshimura, T. (2022). Mechanism of Pyridoxine 5'-Phosphate Accumulation in Pyridoxal 5'-Phosphate-Binding Protein Deficiency. Journal of bacteriology, 204(3), e0052121.     

  20. Ishibashi, Y., Matsushima, N., Ito, T., & Hemmi, H. (2021). Isopentenyl diphosphate/dimethylallyl diphosphate-specific Nudix hydrolase from the methanogenic archaeon Methanosarcina mazei. Bioscience, biotechnology, and biochemistry, 86, 246-253. 

  21. Yasuno, Y., Nakayama, A., Saito, K., Kitsuwa, K., Okamura, H., Komeyama, M., Hemmi, H., & Shinada, T. (2021). Total Synthesis and Structure Confirmation of trans-Anhydromevalonate-5-phosphate, a Key Biosynthetic Intermediate of the Archaeal Mevalonate Pathway. Journal of natural products, 84(10), 2749–2754. 

  22. Ashida, H., Sawa, Y., & Yoshimura, T. (2021). Enzymatic determination of d-alanine with l-alanine dehydrogenase and alanine racemase. Bioscience, biotechnology, and biochemistry, 85(11), 2221–2223. 

  23. Okada M., Unno H., Emi K.-i., Matsumoto M., Hemmi, H. (2021) A versatile cis-prenyltransferase from Methanosarcina mazei catalyzes both C- and O-prenylations. Journal of Biological Chemistry. 296:100679. 

  24. Ito T., Tono M., Kitaura Y., Hemmi H., Yoshimura T. (2021) Urinary L-erythro-β-hydroxyasparagine - a novel serine racemase inhibitor and substrate of the Zn2+-dependent D-serine dehydratase Bioscience Reports 41 (4): BSR20210260. 

  25. Yoshida R., Hemmi H. (2020) Construction of an artificial biosynthetic pathway for hyperextended archaeal membrane lipids in the bacterium Escherichia coli. Synthetic Biology. 5:ysaa018. 

  26. Vu H, Ito T, Downs DM (2020) The role of YggS in vitamin B6 homeostasis in Salmonella enterica is informed by heterologous expression of yeast SNZ3. Journal of Bacteriology. 202(22):e00383-20.  Selected as a Spotlight!

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

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

  29. Yoshida R, Yoshimura T, Hemmi H. (2020) Reconstruction of the "Archaeal" Mevalonate Pathway from the Methanogenic Archaeon Methanosarcina mazei in Escherichia coli Cells.  Appl Environ Microbiol. 86. e02889-19. 

  30. 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.

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Contact

464-8601

Furo-cho, Chikusa, Nagoya, Aichi, Japan


Lab. of Applied Enzymology,

Graduate School of Bioagricultural Sciences,
Nagoya University

Tel: +81-52-789-4132
Fax: +81-52-789-4120
E-mail: hhemmi（＠）agr.nagoya-u.ac.jp
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