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Professor
​
Hisashi HEMMI
​

PhD (Engineering)　

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1993.3. BS in Department of Molecular Chemistry and Engineering, School of Engineering, Tohoku University; 1998.3. PhD in Department of Biomolecular Engineering, Graduate School of Engineering, Tohoku University; 1998.4.-2005.7. Research Associate in Graduate School of Engineering, Tohoku University (2004.9.-2005.6. Visiting Scientist in University of Nebraska-Lincoln); 2005.8.-2022.4. Associate Professor in Graduate School of Bioagricultural Sciences, Nagoya University; 2022.5.- Professor in Graduate School of Bioagricultural Sciences, Nagoya University

Introduction of research themes

Fig. 1　Acidic hot spring in Yellowstone National Park
inset: EM image of a thermoacidophile, Sulfolobus acidocaldarius

fig2.png

Fig. 2 Structures of membrane lipids from archaea (upper) and other organisms (lower) (X represents a hydrophobic head group)

​Archaea are unicellular organisms (Fig. 1), many of which have been isolated from extreme environments such as high temperature and high salt concentrations. They constitute a third group of organisms, along with Eukarya and Bacteria, and thus are of great interest in the evolution of organisms and enzymes. Although this taxonomic grouping (each taxomonic group is referred to as a domain) is based on similarities in the sequence of ribosomal small subunit RNAs, there are many other features that separate Archaea from other groups. One of the characteristics of archaea is the difference in membrane lipid structure from other organisms (Fig. 2). Whereas the glycerolipids of bacteria and eukaryotes have fatty acids as hydrophobic moieties, those of archaea have fully saturated prenyl groups instead. In other words, archaeal membrane lipids belong to a group of compounds called isoprenoids, which are composed of 5-carbon isoprene units. Archaea also synthesize various hydrophobic isoprenoid compounds, such as respiratory chain quinones, carotenoids, and sugar carrier lipids, and therefore isoprenoid biosynthesis in archaea is of great importance. We have identified novel enzymes from thermophilic or methanogenic archaea that catalyze key reactions of isoprenoid lipid metabolism and clarified their properties and reaction mechanisms (Fig. 3). A theory has been proposed that the symbiosis between archaea and bacteria is the origin of eukaryotes, and in fact, many archaeal enzymes have features similar to those of eukaryotes. Therefore, the information obtained from archaeal enzyme research may be valuable in the future, for example, for drug discovery. We are also interested in the role that archaea has played in the development of isoprenoid compounds. We hope to unravel the evolutionary history of organisms, metabolisms, enzymes, and compounds from the perspective of biosynthetic study on archaeal lipids.

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Fig. 3 Isoprenoid biosynthesis in thermophilic archaea (Enzymes that have been studied so far by us are shown in pink.)

Recent Publications

  1. 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. Frontiers in Microbiology,Front Microbiol. 2023;14:1150353. 

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

  3. 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. Journal of Biological Chemistry, 98, 102111. 

  4. Tanaka, Y., Yoshimura, T., Hakamata, M., Saito, C., Sumitani, M., Sezytsu, H, Hemmi, H. & Ito, T. (2022) Identification and characterization of a serine racemase in the silkworm Bombyx mori. Journal of Biochemistry, 172, 17-28. 

  5. 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, 641-651. 

  6. 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. FEBS Journal, 289, 4981-4997. 

  7. 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, 421-428. 

  8. Ito, T., Ogawa, H., Hemmi, H., Downs, D.M. & Yoshimura, T. (2022) Mechanism of pyridoxine 5'-phosphate accumulation in PLPBP protein-deficiency. Journal of Bacteriology, 204, e0052121. 

  9. Ishibashi, Y., Matsushima, N., Ito, T. & Hemmi, H. (2022) Isopentenyl diphosphate/dimethylallyl diphosphate-specific Nudix hydrolase from the methanogenic archaeon Methanosarcina mazei. Bioscience, Biotechnology, and Biochemistry, 86, 246-253. 

  10. 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, 2749-2754. 

  11. 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. 

  12. 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, BSR20210260. 

  13. 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. 

  14. 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. Biochimica et Biophysica Acta - Proteins and Proteomics. 1868:140460. 

  15. Yoshida, R., Yoshimura, T. & Hemmi, H. (2020) Reconstruction of the 'archaeal' mevalonate pathway from the methanogenic archaeon Methanosarcina mazei in Escherichia coli cells. Applied Environmental Microbiology. 86, e02889-19. 

  16. 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. 113, 270-284. 

  17. Emi, K.-i., Sompiyachoke, K., Okada, M. & Hemmi, H. (2019) A heteromeric cis-prenyltransferase is responsible for the biosynthesis of glycosyl carrier lipids in Methanosarcina mazei. Biochemical and Biophysical Research Communications. 520, 291-296. 

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

  19. Motoyama, K., Sobue, F., Kawaide, H., Yoshimura, T. & Hemmi, H. (2019) Conversion of mevalonate 3-kinase into 5-phosphomevalonate 3-kinase by single amino acid mutations. Applied Environmental Microbiology. 85, e00256-19. 

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

  21. Hayashi, Y., Ito, T., Yoshimura, T. & Hemmi, H. (2018) 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. Bioscience, Biotechnology, and Biochemistry. 82, 993-1002. 

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

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

  24. Yoshida, R., Yoshimura, T. & Hemmi, H. (2018) Biosynthetic machinery for C25,C25-diether archaeal lipids from the hyperthermophilic archaeon Aeropyrum pernix. Biochemical and Biophysical Research Communications. 497, 87-92. 

Othres

  • 長瀬研究振興賞（2019年4月）

  • 日本ビタミン学会奨励賞受賞（2010年6月）

  • 酵素応用シンポジウム研究奨励賞受賞（2009年6月）

  • ビタミン・バイオファクター総合事典、朝倉書店（2021年6月刊行、2.2.2 ビタミンB2 構造・化学の執筆を担当）

  • 生体膜の分子機構：リピッドワールドが先導する生命科学、化学同人（2014年11月刊行、第２章「古細菌の膜と脂質」p. 41-62を執筆）

  • Flavins and Flavoproteins 2011, Lulu （2013年3月刊行、国際学会のProceedings： Hemmi, H. and Unno, H., The catalytic role of reduced flavin mononucleotide in type 2 isopentenyl diphosphate isomerase, p. 33-41）

  • Handbook of Flavoproteins: Volume 1ーOxidases, Dehydrogenases and Related Systems, Walter de Gruyter （2012年12月刊行、全２巻のうちの１巻目、第３章を担当： Hemmi, H., Flavoenzymes involved in non-redox reactions, p. 57-73）

  • Comprehensive Natural Product II, Elsevier （2010年1月刊行、全１０巻の大著のうち一部の執筆を担当：Kuzuyama, T., Hemmi, H., & Takahashi, S., Mevalonate Pathway in Bacteria and Archaea, vol.1, p. 493-516）

  • 酵素ハンドブック第３版、朝倉書店（2008年5月刊行、著者多数、一部の酵素について執筆担当）

  • 邊見　久、特集　天然有機化合物の生合成研究が開拓する新しい生物化学の世界「古細菌型メバロン酸経路―その特徴と代謝工学的な応用の可能性―」、生物工学会誌、2024年 第101巻第11号 p.583-586

  • 邊見　久、ミニレビュー「古細菌型メバロン酸経路の発見」、生化学、2021年 第93巻第2号 p.221-224

  • 邊見　久、研究最前線、極限環境生物学会誌、2019年 第17巻 p.3-4

  • 邊見　久、研究紹介「古細菌からの新奇変形メバロン酸経路の発見」、トレーサー、2019年 第65巻 p.2-6

  • 邊見　久、トピックス「大腸菌をプラットフォームとしたアーキア膜脂質生合成研究」、酵素工学ニュース、2016年 第76号 p.11-15

  • 邊見　久、総説「メバロン酸経路の多様性」、バイオサイエンスとインダストリー、2016年 第74巻第1号 p.15-20

  • 邊見　久、今日の話題「好熱性アーキアThermoplasma acidophilumに見いだされた新しいタイプのメバロン酸経路」、化学と生物、2015年 第53巻第3号 p.146-147

  • 邊見　久、ミニレビュー「ユニークなフラビン酵素：タイプ2イソペンテニル二リン酸イソメラーゼ」、生化学、2011年 第83巻第4号 p.304-307

  • 邊見　久、総合論文「古細菌イソプレノイド生合成に関わるタイプ２イソペンテニル二リン酸イソメラーゼにおけるフラビン補酵素の特異な機能」、ビタミン、2011年 第85巻第1号 p.1-8

  • 邊見　久、解説「アーキアにおける膜脂質生合成」、化学と生物、2010年 第48巻第9号 p.614-621

  • 邊見　久、トピックス「イソプレノイド代謝にみるフラビン補酵素のユニークな機能」、バイオサイエンスとインダストリー、2010年 第68巻第6号 p.421-423

  • 邊見　久、バイオミディア「フラビン酵素の新機能？」、生物工学会誌、2010年 第88巻第3号 p.122

  • 邊見　久、総説「タイプ２イソペンテニル二リン酸イソメラーゼの反応機構」、ビタミン、2008年 第82巻第11号 p.581-588

  • 邊見　久、今日の話題「アーキアにおけるイソプレノイド脂質の生合成」、化学と生物、2007年 第45巻第9号 p.596-598

  • 邊見　久、バイオミディア「ホスミドマイシン―抗マラリア薬としての再発見」、生物工学会誌、2000年 第78巻第8号 p.338
     

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