Details of the Researcher

PHOTO

Takuya Kaji
Section
Graduate School of Science
Job title
Assistant Professor
Degree
e-Rad No.
80835520

Research History 4

  • 2019/05 - Present
    Tohoku University　Department of Chemistry　Assistant Professor

  • 2018/04 - 2019/04
    Research Foundation Itsuu Laboratory　Researcher

  • 2017/04 - 2018/03
    University of Toronto

  • 2016/04 - 2017/03
    学術振興会特別研究員DC2

Education 4

  • 東京大学大学院　薬学系研究科　薬科学科 博士課程

    2014/04 - 2017/03

  • 東京大学大学院　薬学系研究科　薬科学科 修士課程

    2012/04 - 2014/03

  • The University of Tokyo　Faculty of Pharmaceutical Sciences　Department of Pharmaceutical Sciences

    2010/04 - 2012/03

  • The University of Tokyo　College of Arts and Sciences

    2008/04 - 2010/03

Professional Memberships 2

  • THE CHEMICAL SOCIETY OF JAPAN

  • THE PHARMACEUTICAL SOCIETY OF JAPAN

Research Areas 3

  • Nanotechnology/Materials / Biochemistry /

  • Nanotechnology/Materials / Molecular biochemistry /

  • Life sciences / Pharmaceuticals - chemistry and drug development /

Awards 1

  1. 日本薬学会第134回年会 優秀発表賞

    2014/03

Papers 21

  1. Advances in the chemical biology of jasmonates

    Takuya Kaji, Yuho Nishizato, Kotaro Matsumoto, Taichi Okumura, Minoru Ueda

    Journal of Experimental Botany　2026/03/27

    Publisher: Oxford University Press (OUP)

    DOI： 10.1093/jxb/erag156 　

    ISSN： 0022-0957

    eISSN： 1460-2431

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    Abstract Plant oxylipins include the jasmonates, lipid-derived hormones that control growth-defense trade-offs. In tracheophytes, (3R, 7S)-jasmonoyl-L-isoleucine (JA-Ile) is the principal bioactive ligand that assembles the COI1–JAZ co-receptor together with inositol polyphosphates, leading to JAZ degradation and transcriptional reprogramming. By contrast, bryophytes employ dn-cis/iso-OPDA and related species, revealing evolutionary diversity in ligand identity and receptor matching. This review synthesizes chemical perspectives on jasmonate signaling. First, we outline the “molecular-glue” logic of COI1–JAZ assembly and the current structural gap beyond Arabidopsis that limits lineage-level, structure-guided discussion. Second, we summarize multilayered metabolic circuits that sculpt signal intensity, duration and spatial distribution: oxidation of JA-Ile to 12-OH- and 12-COOH-JA-Ile; hydrolysis; and hydroxylation of the JA backbone. Notably, 12-OH-JA-Ile can function as a weak and “biased” agonist, whereas 12-COOH-JA-Ile is receptor-silent; in Marchantia, dn-iso-OPDA is chiefly inactivated by conjugation with amino acids, paralleling auxin logic. Third, we review evidence for co-evolution of ligands with COI1/JAZ components across land plants. Finally, we highlight the design of COI1-JAZ subtype-selective agonists and antagonists—often based on coronatine scaffolds—that preferentially recruit specific JAZ proteins to promote ERF/ORA outputs while sparing MYC-branch responses. These chemical levers suggest practical routes to amplify defense with reduced growth costs, offering opportunities for stress-resilient crop improvement.

  2. Distinct OPDA Biosynthesis Pathways in the Liverwort Marchantia polymorpha and the Moss Physcomitrium patens

    Yuho Nishizato, Yuki Hata, Takuya Kaji, Mai Morikawa, Junko Kyozuka, Minoru Ueda

    Journal of Plant Growth Regulation　2026/01/09

    Publisher: Springer Science and Business Media LLC

    DOI： 10.1007/s00344-025-12041-7 　

    ISSN： 0721-7595

    eISSN： 1435-8107

  3. (3R, 7S)-11-hydroxy-jasmonic acid is a major oxidative shunt product of jasmonic acid catabolism in Arabidopsis thaliana

    Minoru Ueda, Kotaro Matsumoto, Maria Mitsui, Takuya Kaji, Naoki Kitaoka, Riqui Gao, Taketomo Otaki, Yuho Nishizato, Hideyuki Matsuura

    2025/11/06

    Publisher: Springer Science and Business Media LLC

    DOI： 10.21203/rs.3.rs-7856590/v1 　

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    Abstract <p>Jasmonoyl-L-isoleucine (JA-Ile) is a pivotal oxylipin hormone that coordinates growth-defense trade-offs, and its precursor jasmonic acid (JA) is therefore subject to tight metabolic control. For more than a decade, the prevailing dogma held that jasmonate turnover is dominated by C12-hydroxylation, with JOX dioxygenases acting on JA and CYP94 monooxygenases acting on JA-Ile. Here we revise this dogma by showing that hydroxylation at the C11 position constitutes a major receptor-silent deactivation shunt of JA turnover.Using chemically synthesized (3R,7S)-11-hydroxy-JA (11-OH-JA) of naturally occurring stereochemistry as a standard, we unambiguously identify 11-OH-JA as the principal shunt product that accumulates in wounded Arabidopsis thaliana. In vitro enzymatic assays and in silico docking revealed that JOX1/2/3/4 exclusively converted JA to 11-OH-JA, whereas 12-OH-JA arose from distinct pathway. Consistently, the jox quadruple mutant (joxQ) abolished 11-OH-JA accumulation without affecting 12-OH-JA levels. Moreover, 11-OH-JA failed to bind the COI1–JAZ co-receptor, establishing it as a biologically inactive endpoint of JA catabolism.These findings correct a long-standing misattribution of the JOX product to 12-OH-JA and redefine the metabolic framework of jasmonate. Parallel, non-redundant inactivation routes deliver layered signal termination of costly defense signals. This study provides new insights into JA catabolism, highlighting 11-OH-JA as a crucial factor in the attenuation of jasmonate signaling, and thereby redefining the framework of JA turnover in A. thaliana.</p>

  4. Amide conjugates of the jasmonate precursor cis-OPDA regulate its homeostasis during plant stress responses

    Jitka Široká, Anita Ament, Václav Mik, Tomáš Pospíšil, Michaela Kralová, Chao Zhang, Markéta Pernisová, Michal Karady, Vladimira Nožková, Yuho Nishizato, Takuya Kaji, Rina Saito, Mohamed Htitich, Kristýna Floková, Claus Wasternack, Miroslav Strnad, Minoru Ueda, Ondřej Novák, Federica Brunoni

    Plant Physiology　2024/11/28

    Publisher: Oxford University Press (OUP)

    DOI： 10.1093/plphys/kiae636 　

    ISSN： 0032-0889

    eISSN： 1532-2548

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    Abstract Jasmonates (JAs) are a family of oxylipin phytohormones regulating plant development and growth and mediating ‘defense versus growth’ responses. The upstream JA biosynthetic precursor cis-(+)-12-oxo-phytodienoic acid (cis-OPDA) acts independently of CORONATIVE INSENSITIVE 1 (COI1)-mediated JA signaling in several stress-induced and developmental processes. However, its perception and metabolism are only partially understood. A few years ago, a low abundant isoleucine analog of the biologically active JA-Ile, OPDA-Ile, was detected years ago in wounded leaves of flowering plants, opening up the possibility that conjugation of cis-OPDA to amino acids might be a relevant mechanism for cis-OPDA regulation. Here, we extended the analysis of amino acid conjugates of cis-OPDA and identified naturally occurring OPDA-Val, OPDA-Phe, OPDA-Ala, OPDA-Glu, and OPDA-Asp accumulating in response to biotic and abiotic stress in Arabidopsis (Arabidopsis thaliana). The OPDA-amino acid conjugates displayed cis-OPDA-related plant responses in a JA-Ile-dependent manner. We also showed that the synthesis and hydrolysis of cis-OPDA amino acid conjugates are mediated by members of the amidosynthetase GRETCHEN HAGEN 3 (GH3) and the amidohydrolase INDOLE-3-ACETYL-LEUCINE RESISTANT 1 (ILR1)/ILR1-like (ILL) families. Thus, OPDA amino acid conjugates function in the catabolism or temporary storage of cis-OPDA in stress responses instead of acting as chemical signals per se.

  5. Conjugation of dn-OPDA with amino acids inhibits its hormonal bioactivity in Marchantia polymorpha

    Wenting Liang, Angel Maria Zamarreño, Salvador Torres-Montilla, Antonio de la Torre, Jean Chrisologue Totozafy, Takuya Kaji, Minoru Ueda, Massimiliano Corso, Jose Maria Garcia-Mina, Roberto Solano, Andrea Chini

    2024/08/30

    Publisher: Cold Spring Harbor Laboratory

    DOI： 10.1101/2024.08.27.609933 　

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    Jasmonates are important phytohormones activating plant tolerance to biotic and abiotic stress, as well as different development processes. A conserved signalling pathway activated by distinct hormones in different plant species mediates these responses: dinor-12-oxo-phytodienoic acid (dn-OPDA) isomers in bryophytes and lycophytes, and JA-Ile in most vascular plants. The final responses depend, in many cases, on the accumulation of specialized metabolites. To identify novel compounds regulated by the dn-OPDA pathway in Marchantia, untargeted metabolomic analyses were carried out in response to dn-OPDA-regulated stress. A novel group of molecules were identified as dn-OPDA-amino acid conjugates (dn-OPDA-aas), and their accumulation after wounding and herbivory confirmed by targeted metabolic profiling in Marchantia and all species in which we previously found dn-iso-OPDA. Mutants in GRETCHEN-HAGEN 3A (MpGH3A) failed to accumulate dn-OPDA-aa conjugates, and showed a constitutive activation of the OPDA pathway and increased resistance to herbivory. Our results show that dn-iso-OPDA bioactivity is reduced by conjugation with amino acids. Therefore, a dichotomous role of jasmonate conjugation in land plants is highlighted: jasmonic acid (JA) conjugation with isoleucine (Ile) produce the bioactive JA-Ile in tracheophytes, whereas conjugation of dn-iso-OPDA with different amino acids disactivate the hormone in bryophytes and lycophytes.

  6. SlCYP94B18 and SlCYP94B19 monooxygenases for the catabolic turnover of jasmonates in tomato leaves Peer-reviewed

    Rina Saito, Mai Morikawa, Toshiya Muto, Sayaka Saito, Takuya Kaji, Minoru Ueda

    Phytochemistry　2024/07

    DOI： 10.1016/j.phytochem.2024.114141 　

  7. Δ4-dn-iso-OPDA, a bioactive plant hormone of Marchantia polymorpha

    Takuya Kaji, Yuho Nishizato, Hidenori Yoshimatsu, Akiyoshi Yoda, Wenting Liang, Andrea Chini, Gemma Fernández-Barbero, Kei Nozawa, Junko Kyozuka, Roberto Solano, Minoru Ueda

    iScience　110191-110191　2024/06

    Publisher: Elsevier BV

    DOI： 10.1016/j.isci.2024.110191 　

    ISSN： 2589-0042

  8. Identification of “modified OPDA (mo-OPDA)” as a Michael adduct of cis-OPDA

    Yuho Nishizato, Yuki Muraoka, Mai Morikawa, Rina Saito, Takuya Kaji, Minoru Ueda

    Bioscience, Biotechnology, and Biochemistry　2024/05/02

    Publisher: Oxford University Press (OUP)

    DOI： 10.1093/bbb/zbae056 　

    eISSN： 1347-6947

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    Abstract cis-(+)-12-Oxo-phytodienoic acid (cis-OPDA) is a significant plant oxylipin, known as a biosynthetic precursor of plant hormone jasmonoyl-L-isoleucine (JA-Ile), and a bioactive substance in plant environmental stresses. A recent study showed that a plant monooxygenase a plant dioxygenase, Jasmonate Induced Dioxygenase 1 (JID1), converts cis-OPDA into an unidentified metabolite termed “modified-OPDA (mo-OPDA)” in Arabidopsis thaliana. Here, using UPLC-MS/MS experiment, the chemical identity of “mo-OPDA” was demonstrated and identified as a conjugate between cis-OPDA and 2-mercaptoethanol (cis-OPDA-2ME), an artifact produced by Michael addition during the JID1 digestion of cis-OPDA. However, previous reports demonstrated a decreased accumulation of cis-OPDA in the JID1-OE line, suggesting the existence of an unknown JID1-mediated mechanism regulating the level of cis-OPDA in A. thaliana.

  9. Two distinct modes of action of molecular glues in the plant hormone co-receptor COI1-JAZ system

    Takuya Kaji, Kotaro Matsumoto, Taichi Okumura, Misuzu Nakayama, Shunji Hoshino, Yousuke Takaoka, Jianxin Wang, Minoru Ueda

    iScience　108625-108625　2023/12

    Publisher: Elsevier BV

    DOI： 10.1016/j.isci.2023.108625 　

    ISSN： 2589-0042

  10. Difference in the ligand affinity among redundant plant hormone receptors of rice OsCOI1a/1b/2-OsJAZs. International-journal

    Taichi Okumura, Tsumugi Kitajima, Takuya Kaji, Haruyuki Urano, Kotaro Matsumoto, Hideo Inagaki, Koji Miyamoto, Kazunori Okada, Minoru Ueda

    Bioscience, biotechnology, and biochemistry　2023/07/04

    DOI： 10.1093/bbb/zbad092 　

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    (3R, 7S)-jasmonoyl-L-isoleucine (JA-Ile) is a lipid-derived plant hormone that regulates plant responses, including biotic/abiotic stress adaptation. In the plant cells, JA-Ile is perceived by COI1-JAZ co-receptor by causing protein-protein interaction between COI1 and JAZ proteins to trigger gene expressions. In this study, we focused on Oryza sativa, a model monocot and an important crop, with 45 possible OsCOI-OsJAZ co-receptor pairs composed of three OsCOI homologs (OsCOI1a, OsCOI1b, and OsCOI2) and 15 OsJAZ homologs. We performed fluorescein anisotropy and pull-down assays to examine the affinity between JA-Ile and OsCOI1a/1b/2-OsJAZ1-15 co-receptor pairs. The results revealed a remarkable difference in the modes of ligand perception by OsCOI1a/1b and OsCOI2. Recently, the unique function of OsCOI2 in some of the JA-responses were revealed. Our current results will lead to the possible development of OsCOI2-selective synthetic ligand.

  11. Deciphering OPDA Signaling Components in the Momilactone-Producing Moss Calohypnum plumiforme. International-journal

    Hideo Inagaki, Koji Miyamoto, Noriko Ando, Kohei Murakami, Koki Sugisawa, Shion Morita, Emi Yumoto, Miyu Teruya, Kenichi Uchida, Nobuki Kato, Takuya Kaji, Yousuke Takaoka, Yuko Hojo, Tomonori Shinya, Ivan Galis, Akira Nozawa, Tatsuya Sawasaki, Hideaki Nojiri, Minoru Ueda, Kazunori Okada

    Frontiers in plant science　12　688565-688565　2021

    DOI： 10.3389/fpls.2021.688565 　

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    Jasmonic acid (JA) and its biologically active form jasmonoyl-L-isoleucine (JA-Ile) regulate defense responses to various environmental stresses and developmental processes in plants. JA and JA-Ile are synthesized from α-linolenic acids derived from membrane lipids via 12-oxo-phytodienoic acid (OPDA). In the presence of JA-Ile, the COI1 receptor physically interacts with JAZ repressors, leading to their degradation, resulting in the transcription of JA-responsive genes by MYC transcription factors. Although the biosynthesis of JA-Ile is conserved in vascular plants, it is not recognized by COI1 in bryophytes and is not biologically active. In the liverwort Marchantia polymorpha, dinor-OPDA (dn-OPDA), a homolog of OPDA with two fewer carbons, and its isomer dn-iso-OPDA accumulate after wounding and are recognized by COI1 to activate downstream signaling. The moss Calohypnum plumiforme produces the antimicrobial-specialized metabolites, momilactones. It has been reported that JA and JA-Ile are not detected in C. plumiforme and that OPDA, but not JA, can induce momilactone accumulation and the expression of these biosynthetic genes, suggesting that OPDA or its derivative is a biologically active molecule in C. plumiforme that induces chemical defense. In the present study, we investigated the biological functions of OPDA and its derivatives in C. plumiforme. Searching for the components potentially involving oxylipin signaling from transcriptomic and genomic data revealed that two COI1, three JAZ, and two MYC genes were present. Quantification analyses revealed that OPDA and its isomer iso-OPDA accumulated in larger amounts than dn-OPDA and dn-iso-OPDA after wounding. Moreover, exogenously applied OPDA, dn-OPDA, or dn-iso-OPDA induced the transcription of JAZ genes. These results imply that OPDA, dn-OPDA, and/or their isomers potentially act as biologically active molecules to induce the signaling downstream of COI1-JAZ. Furthermore, co-immunoprecipitation analysis showed the physical interaction between JAZs and MYCs, indicating the functional conservation of JAZs in C. plumiforme with other plants. These results suggest that COI1-JAZ-MYC mediated signaling is conserved and functional in C. plumiforme.

  12. Syntheses of dinor-cis/iso-12-oxo-phytodienoic acid (dn-cis/iso-OPDAs), ancestral jasmonate phytohormones of the bryophyte Marchantia polymorpha L., and their catabolites

    Jianxin Wang, Haruka Sakurai, Nobuki Kato, Takuya Kaji, Minoru Ueda

    SCIENTIFIC REPORTS　11　(1)　2021/01

    DOI： 10.1038/s41598-021-81575-z 　

    ISSN： 2045-2322

  13. Recent Advances in Plant Chemical Biology of Jasmonates. International-journal Peer-reviewed

    Minoru Ueda, Takuya Kaji, Wataru Kozaki

    International journal of molecular sciences　21　(3)　2020/02/07

    DOI： 10.3390/ijms21031124 　

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    Lipid-derived plant hormone jasmonates are implicated in plant growth, reproductive performance, senescence, secondary metabolite productions, and defense against both necrotrophic pathogens and feeding insects. A major jasmonate is (+)-7-iso-jasmonoyl-l-isoleucine (JA-Ile), which is perceived by the unique COI1-JAZ coreceptor system. Recent advances in plant chemical biology have greatly informed the bioscience of jasmonate, including the development of chemical tools such as the antagonist COR-MO; the agonist NOPh; and newly developed jasmonates, including JA-Ile-macrolactone and 12-OH-JA-Ile. This review article summarizes the current status of plant chemical biology as it pertains to jasmonates, and offers some perspectives for the future.

  14. Development of a high-throughput strategy for discovery of potent analogues of antibiotic lysocin E. International-journal Peer-reviewed

    Hiroaki Itoh, Kotaro Tokumoto, Takuya Kaji, Atmika Paudel, Suresh Panthee, Hiroshi Hamamoto, Kazuhisa Sekimizu, Masayuki Inoue

    Nature communications　10　(1)　2992-2992　2019/07/05

    DOI： 10.1038/s41467-019-10754-4 　

    ISSN： 2041-1723

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    Lysocin E, a 37-membered natural depsipeptide, induces rapid bacteriolysis in methicillin-resistant Staphylococcus aureus via a unique menaquinone-dependent mechanism, presenting a promising therapeutic lead. Despite the great medical importance, exploring the potential utility of its derivatives as new platform structures for antibiotic development has remained a significant challenge. Here, we report a high-throughput strategy that enabled the preparation of thousands of analogues of lysocin E and large-scale structure-activity relationship analyses. We integrate 26-step total synthesis of 2401 cyclic peptides, tandem mass spectrometry-sequencing, and two microscale activity assays to identify 23 candidate compounds. Re-synthesis of these candidates shows that 11 of them (A1-A11) exhibit antimicrobial activity superior or comparable to that of lysocin E, and that lysocin E and A1-A11 share L-Leu-6 and L-Ile-11. Therefore, the present strategy allows us to efficiently decipher biologically crucial residues and identify potentially useful agents for the treatment of infectious diseases.

  15. Total Synthesis and Biological Mode of Action of WAP-8294A2: A Menaquinone-Targeting Antibiotic. International-journal Peer-reviewed

    Hiroaki Itoh, Kotaro Tokumoto, Takuya Kaji, Atmika Paudel, Suresh Panthee, Hiroshi Hamamoto, Kazuhisa Sekimizu, Masayuki Inoue

    The Journal of organic chemistry　83　(13)　6924-6935　2018/07/06

    DOI： 10.1021/acs.joc.7b02318 　

    ISSN： 0022-3263

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    WAP-8294A2 (lotilibcin, 1) is a potent antibiotic with superior in vivo efficacy to vancomycin against methicillin-resistant Staphylococcus aureus (MRSA). Despite the great medical importance, its molecular mode of action remains unknown. Here we report the total synthesis of complex macrocyclic peptide 1 comprised of 12 amino acids with a β-hydroxy fatty-acid chain, and its deoxy analogue 2. A full solid-phase synthesis of 1 and 2 enabled their rapid assembly and the first detailed investigation of their functions. Compounds 1 and 2 were equipotent against various strains of Gram-positive bacteria including MRSA. We present evidence that the antimicrobial activities of 1 and 2 are due to lysis of the bacterial membrane, and their membrane-disrupting effects depend on the presence of menaquinone, an essential factor for the bacterial respiratory chain. The established synthetic routes and the menaquinone-targeting mechanisms provide valuable information for designing and developing new antibiotics based on their structures.

  16. Development of Endocyclic Control Elements for Peptide Macrocycles Peer-reviewed

    Solomon D. Appavoo, Takuya Kaji, John R. Frost, Conor C. G. Scully, Andrei K. Yudin

    Journal of the American Chemical Society　140　(28)　8763-8770　2018/06

    Publisher: American Chemical Society ({ACS})

    DOI： 10.1021/jacs.8b04412 　

    ISSN： 0002-7863

  17. Total Synthesis and Functional Evaluation of Fourteen Derivatives of Lysocin E: Importance of Cationic, Hydrophobic, and Aromatic Moieties for Antibacterial Activity Peer-reviewed

    Takuya Kaji, Motoki Murai, Hiroaki Itoh, Jyunichiro Yasukawa, Hiroshi Hamamoto, Kazuhisa Sekimizu, Masayuki Inoue

    CHEMISTRY-A EUROPEAN JOURNAL　22　(47)　16910-16917　2016/11

    DOI： 10.1002/chem.201604022 　

    ISSN： 0947-6539

    eISSN： 1521-3765

  18. Lysocin E is a new antibiotic that targets menaquinone in the bacterial membrane Peer-reviewed

    Hiroshi Hamamoto, Makoto Urai, Kenichi Ishii, Jyunichiro Yasukawa, Atmika Paudel, Motoki Murai, Takuya Kaji, Takefumi Kuranaga, Kenji Hamase, Takashi Katsu, Jie Su, Tatsuo Adachi, Ryuji Uchida, Hiroshi Tomoda, Maki Yamada, Manabu Souma, Hiroki Kurihara, Masayuki Inoue, Kazuhisa Sekimizu

    NATURE CHEMICAL BIOLOGY　11　(2)　127-U68　2015/02

    DOI： 10.1038/NCHEMBIO.1710 　

    ISSN： 1552-4450

    eISSN： 1552-4469

  19. Total Synthesis and Biological Evaluation of the Antibiotic Lysocin E and Its Enantiomeric, Epimeric, and N-Demethylated Analogues Peer-reviewed

    Motoki Murai, Takuya Kaji, Takefumi Kuranaga, Hiroshi Hamamoto, Kazuhisa Sekimizu, Masayuki Inoue

    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION　54　(5)　1556-1560　2015/01

    DOI： 10.1002/anie.201410270 　

    ISSN： 1433-7851

    eISSN： 1521-3773

  20. Total Synthesis and Biological Evaluation of the Antibiotic Lysocin E and Its Enantiomeric, Epimeric, and N-Demethylated Analogues

    Motoki Murai, Takuya Kaji, Takefumi Kuranaga, Hiroshi Hamamoto, Kazuhisa Sekimizu, Masayuki Inoue

    Angewandte Chemie　127　(5)　1576-1580　2014

    Publisher: Wiley

    DOI： 10.1002/ange.201410270 　

    ISSN： 0044-8249

  21. A heptaketide naphthaldehyde produced by a polyketide synthase from Nectria haematococca Peer-reviewed

    Takayoshi Awakawa, Takuya Kaji, Toshiyuki Wakimoto, Ikuro Abe

    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS　22　(13)　4338-4340　2012/07

    DOI： 10.1016/j.bmcl.2012.05.005 　

    ISSN： 0960-894X

Show all ︎Show first 5

Misc. 7

  1. Development of rice jasmonate receptor subtype-selective synthetic ligands

    三井麻里有, 奥村太知, 北島紬, 加治拓哉, 林謙吾, 稲垣秀生, 宮本皓司, 岡田憲典, 上田実, 上田実

    日本化学会春季年会講演予稿集(Web)　104th　2024

  2. Screening of rice jasmonate receptor subtype-selective ligands from coronatine analogues.

    北島紬, 奥村太知, 加治拓哉, 三井麻里有, 林謙吾, 浦野晴行, 松本幸太郎, 稲垣秀生, 宮本皓司, 岡田憲典, 上田実

    植物の生長調節　58　(Supplement)　2023

    ISSN： 1346-5406

  3. Development of receptor subtype selective ligands via focused library screening composed of stereoisomers of coronatine

    林謙吾, 加藤信樹, 野本春菜, 中山美涼, 加治拓哉, 渡部楽, 齊藤里菜, 高岡洋輔, 宮本皓司, 稲垣秀生, 岡田憲典, 上田実

    日本化学会春季年会講演予稿集(Web)　101st　2021

  4. Research on functional difference of jasmonate receptors in rice

    稲垣秀生, 湯本絵美, 朝比奈雅志, 内田健一, 朝比奈雅志, 内田健一, 林謙吾, 加治拓哉, 高岡洋輔, 上田実, 岡田憲典, 山根久和, 山根久和, 宮本皓司

    植物の生長調節　55　(Supplement)　2020

    ISSN： 1346-5406

  5. Development of receptor subtype selective ligands via focused library screening composed of stereoisomers of coronatine

    林謙吾, 加藤信樹, 渡部楽, 高岡洋輔, 野本春菜, 中山美涼, 宮川咲季, 宮本皓司, 稲垣秀生, 岡田憲典, 加治拓哉, 上田実

    天然有機化合物討論会講演要旨集(Web)　62nd　2020

    ISSN： 2433-1856

  6. Screening of stereochemical library of coronatine for development of the target subtype selective ligand

    林謙吾, 加藤信樹, 渡部楽, 宮本皓司, 稲垣秀生, 岡田憲典, 齊藤里菜, 山神壮平, 野本春菜, 中山美涼, 加治拓哉, 上田実

    万有仙台シンポジウム　31st　2020

  7. Total synthesis and structure-function relationship study of kaikosins

    Kaji Takuya, Murai Motoki, Kuranaga Takefumi, Hamamoto Hiroshi, Sekimizu Kazuhisa, Inoue Masayuki

    Symposium on the Chemistry of Natural Products, symposium papers　56　(0)　2014

    Publisher: Symposium on the Chemistry of Natural Products Steering Committee

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    &lt;p&gt; Infectious diseases caused by antibiotic-resistant bacteria pose a threat to public health around the world. Nosocomial infections caused by methicillin-resistant Staphylococcus aureus (MRSA) in hospitals have become an especially serious clinical problem. Kaikosin E (1a) is a novel antimicrobial peptide isolated from a culture supernatant of a Lysobacter species. Peptide 1a possesses a 37-membered cyclic depsipeptide core structure, comprising twelve amino acid residues with an N-methylated amide and an ester linkage. There are four types of D-configured amino acids (D-Gln, D-Trp, D-Arg, N-Me-D-Phe) within the sequence, and (R)-3-hydroxy-5-methylhexanamide is appended to the macrocyclic core. Peptide 1a exhibited a potent growth inhibition of MRSA with minimum inhibitory concentration (MIC) of 4 μg/mL. Furthermore, 1a was found to possess a potent therapeutic effect in S. aureus-infected mice. The ED&lt;sub&gt;50&lt;/sub&gt; value of 1a (0.5 mg/kg) was even smaller than that of vancomycin (5.8 mg/kg), which is widely used in MRSA infections. &lt;/p&gt;&lt;p&gt;Menaquinone (2), a co-enzyme in the bacterial respiratory chain, has been assumed to be the target of 1a. Peptide 1a selectively forms an equimolar complex with menaquinone present in the cytoplasmic membrane, effecting cell death through membrane disruption. Peptide 1a is viewed as a useful lead compound en route to an optimal drug candidate. Thus further investigation is needed to elucidate its precise molecular mode of action. Detailed structure-function relationship study is also necessitated in order to reveal the structural requirements to exert its bioactivities.&lt;/p&gt;

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Research Projects 7

  1. Ancestral plant hormone and molecular evolution of plant hormone signaling

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))

    Institution: Tohoku University

    2022/10/07 - 2025/03/31

  2. 原始植物ホルモン受容体-リガンドを用いた人工的逆進化によるジャスモン酸応答制御

    加治 拓哉

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 若手研究

    Institution: 東北大学

    2022/04/01 - 2025/03/31

  3. Chemical biology of natural products on plant hormones

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (A)

    Institution: Tohoku University

    2020/04/01 - 2023/03/31

  4. Molecular mechanism of action of JA analogue which selectively enhances antiherbivore defense in Solanaceae plants

    Kaji Takuya

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Early-Career Scientists

    Institution: Tohoku University

    2020/04/01 - 2022/03/31

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    Plant hormone JA-Ile induces defense response against insects and pathogens, but also induces growth inhibition. Jasmonoyl-L-isoleucine lacton (JILa), which is a synthetic lactone analogue of JA-Ile, was reported to show defense response without causing growth inhibition against tobacco. However, detailed mechanism of action remained elucive. In this study, we conducted bioactivity measurements and in-vitro biochemical mechanistic analysis using tomato, the same Solanaceae model plant as tobacco. Our results suggested that JILa induced tomatine accumulation, and the bioactive form of JILa was suggested as its hydrolysate, 12-OH-JA-Ile. In-vitro assay and gene expression analysis suggested that 12-OH-JA-Ile would selectively activate partial jasmonate signaling through receptor subtype selective binding activity.

  5. Regulation of plant hormone receptor using stereochemical isomers of a natural product

    UEDA Minoru

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))

    Institution: Tohoku University

    2019/02/07 - 2022/03/31

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    A stereoisomer library of phytotoxins was constructed by chemical synthesis, and a comprehensive evaluation of their affinity for phytohormone receptor subtypes and their biological activity was conducted in an international collaboration with CNB-CSIC, Spain. The stereoisomer library was evaluated using three plant species, Arabidopsis thaliana, tomato, and rice, and we succeeded in finding stereoisomers each showing unique selective affinity to nuclear receptor subtypes. In this study, we focused on stereoisomers that showed affinity to the receptor subtypes in Arabidopsis thaliana and analyzed their mechanisms of action in detail. As a result, we succeeded in developing molecules that selectively activate receptor subtypes of phytohormone receptors that are involved in the induction of plant resistance to microbial infection.The molecule selectively activates only a portion of phytohormone signaling, while suppression of gene expression does not occur to any degree.

  6. Studies on chemical communication on host-selective toxins

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

    Institution: Tohoku University

    2017/06/30 - 2022/03/31

  7. 抗菌ペプチド天然物ライソシンを基盤とした構造機能相関研究

    加治 拓哉

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 特別研究員奨励費

    Category: 特別研究員奨励費

    Institution: 東京大学

    2016/04/22 - 2018/03/31

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    ４月中は研究計画に従い、ライソシン類の構造活性相関研究に取り組んだ。前年度、これまで構造活性相関研究を行なっていなかった４箇所のアミノ酸（３残基目のセリン、６残基目のロイシン、９残基目のグルタミン、１１残基目のイソロイシン）の側鎖構造をランダム化したOBOCライブラリを作成し、アッセイを行った。その結果、天然物の配列を含む２６個のペプチド配列を高いメナキノンへの親和性と抗菌活性を有するライソシン類縁体の候補として見出していた。得られた候補配列の内、１３個の配列からなる新規ライソシン類縁体についてさらなる機能評価、解析を行うためにスケールアップ合成を実施した。合成した類縁体を抗菌活性評価に供した結果、天然物と同等の抗菌活性を有するものが含まれることを明らかにした。 ５月からは計画を変更し、学振PDの海外渡航制度により、環状ペプチド類の溶液構造解析や配座固定効果に関する知識・経験の習得を目的として、トロント大学化学科のYudin研にて環状ペプチドの構造機能相関研究に従事した。Yudin研では最近、N-(isocyanimino)-triphenylphospharane (Pinc)試薬を用いることで直鎖ペプチドを液相１工程にてオキサジアゾール/アミン構造を形成しながら環化することが出来ることを報告している。この反応で導入されるリンカー構造が、脂溶性の向上や分子内水素結合安定化による配座固定効果など、単純な環状ペプチド化合物に対し有用な特性を有することが示唆された。そこで、本リンカー構造による配座効果のさらなる検証を行なった。新たに合成した環状ペプチド類はいずれもβターン構造を主要な溶液構造として取ることが温度可変NMR測定や分子動力学計算などから示唆され、また、導入されたアミン部位が分子内水素結合に関与していることを明らかにした。

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