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

 

This paper is the first to demonstrate that the archaeal mevalonate pathway also exists in bacteria. The discovery was made in uncultured bacteria whose genomes were reconstructed from environmental metagenomics, and it is particularly interesting that these bacteria belong to the Chloroflexus phylum, which also includes bacteria with another modified mevalonate pathway, the haloarchaea-type mevalonate pathway, or the non-mevalonate pathway (the methylerythritol phosphate pathway). It seems necessary to consider, in conjunction with the evolution of enzymes and metabolic pathways, why bacteria in this group possess such diverse isoprenoid precursor biosynthesis pathways.

       FEBS Journal (2026) doi:10.1111/febs.70412

 

The archaeal mevalonate pathway is a modified metabolic pathway that we have discovered. It has attracted attention because it is thought to be the ancestral form of the mevalonate pathway, which has multiple variations, and because it consumes less ATP than other mevalonate pathways, making it promising for metabolic engineering applications. In this paper, we are the first to elucidate the enzymatic properties of anhydromevalonate phosphate decarboxylase, which is included in this pathway. This enzyme requires a coenzyme called prenylated flavin mononucleotide (prFMN) for its reaction, and this paper also discusses the prFMN-dependent reaction mechanism of this enzyme based on the results of by-product analysis.

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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. Chen, X., Nakanishi, M., Han, J., Hemmi, H. and Chen, F. (2026) Evolution of trans-isoprenyl diphosphate synthases in the plant kingdom. Plant Physiology, in press, doi: 10.1093/plphys/kiag238

  2. Kito, N., Kitaura, Y., Iino, K., Toriumi, K., Noh, H., Ogawa, N., Arai, M., Hemmi, H. and 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

  3. Munaweera K, Odake N, Halim HP, Ikeda K, Zhu B, Camagna M, Ito T, Kitaguchi T, Nemoto N, Nakano H, Damnjanović J. (2026) Harnessing the Power of SMART Single-Molecule Display for Enzyme Evolution: A Focus on Oxidase. ACS Synth Biol. 2026 Feb 23. doi: 10.1021/acssynbio.5c00968.

  4. 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.​

  5. 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​

  6. Hata A, Ito T, Mori H, Ogawa T, Kurihara T, Hemmi H, Yoshimura T. Suicide substrate reaction-like modification of mouse serine racemase with L-serine. J Biochem. 2025, 177(6):437-445.​​

  7. 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 

  8. ​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

  9. 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

  10. 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. 

  11. 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.

  12. 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.  

  13. 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 

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

  15. 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 

  16. 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!)

  17. 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. 

  18. 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. 

  19. 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. 

  20. 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.     

  21. 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. 

  22. 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. 

  23. 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. 

  24. 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. 

  25. 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. 

  26. 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. 

  27. 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!

  28. 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. 

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

  30. 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. 

  31. 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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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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