Chemical communications in microbial interactions and development of useful bioactive ligands

• Project Area: Frontier research of chemical communications
• Project/Area Number: 17H06401
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Science and Engineering
• Research Institution: Kyoto University
• Principal Investigator: 掛谷 秀昭 京都大学, 薬学研究科, 教授 (00270596)
• Co-Investigator(Kenkyū-buntansha): 井本 正哉 順天堂大学, 医学(系)研究科(研究院), 特任教授 (60213253) ; 西村 慎一 東京大学, 大学院農学生命科学研究科(農学部), 講師 (30415260)
• Project Period (FY): 2017-06-30 – 2022-03-31
• Project Status: Granted (Fiscal Year 2021)
• Budget Amount: ¥104,910,000 (Direct Cost: ¥80,700,000、Indirect Cost: ¥24,210,000); Fiscal Year 2021: ¥21,450,000 (Direct Cost: ¥16,500,000、Indirect Cost: ¥4,950,000); Fiscal Year 2020: ¥21,450,000 (Direct Cost: ¥16,500,000、Indirect Cost: ¥4,950,000); Fiscal Year 2019: ¥21,450,000 (Direct Cost: ¥16,500,000、Indirect Cost: ¥4,950,000); Fiscal Year 2018: ¥21,450,000 (Direct Cost: ¥16,500,000、Indirect Cost: ¥4,950,000); Fiscal Year 2017: ¥19,110,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥4,410,000)
• Keywords: 化学コミュニケーション / 天然物化学 / 複合培養 / 生物活性リガンド / 生合成

Outline of Annual Research Achievements

微生物が産生する二次代謝産物は、歴史上、有用なケミカルツール分子や創薬シーズになっている。しかし、これら二次代謝産物の本来の化学コミュニケーションに基づいた生物学的意義はほとんど解明されていない。そこで、本研究代表者らが見出した新規抗生物質5aTHQs及びSTAMsを生産可能な放線菌Streptomyces sp. HEK616とTsukamurella pulmonis TP-0596の複合培養系に加えて、複数の有用な複合培養系を確立した。特に、T. pulmonis TP-0596と希少放線菌Amicolatopsis sp. 26-4との複合培養により、高度に酸化された側鎖を有する新規環状デプシペプチドamycolapeptins A及びBを見出し、その化学構造を決定した。一方、引き続き、新規熱ショック代謝産物（HSMs）の探索研究と生合成機構の解析研究を行った。
さらに、本研究代表者らが開発した高感度ラベル化剤を活用したHighly-sensitive (HS)-advanced Marfey法を応用することで、極微量の化学コミュニケーション分子の検出に成功した。一方、領域内連携を活用して、引き続き、ベルコペプチンの細胞内化学シグナルの解析のためのケミカルジェネティクス的アプローチを行うとともに、がん幹細胞選択的に細胞死を誘導する複数の生物活性リガンドを見出した。さらに、ショウガ科ウコン由来のポリフェノール化合物であるクルクミンのプロドラッグ型水溶性化合物CMGが神経炎症の緩和に有効であることを明らかにした。

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

微生物間化学コミュニケーションの理解に有用な微生物の複合培養系のモデル系として、Streptomyces sp. HEK616とTsukamurella pulmonis TP-0596の系に加えて、新たに複数の有用な複合培養系を確立できたとともに、複数のHSMsの同定に成功した。特に、希少放線菌Amicolatopsis sp. 26-4との複合培養により、新規環状デプシペプチドamycolapeptins A及びBを見出した。一方、本研究代表者らが開発したHS-advanced Marfey法を応用することで、極微量の化学コミュニケーション分子の探索・同定に成功した。さらに、有用生物活性リガンドの開拓研究においても、がん幹細胞選択的に細胞死を誘導する複数の生物活性リガンドを見出すとともに、革新的プロドラッグ型抗がん剤CMGが神経炎症緩和効果を示すことを明らかにした。

Strategy for Future Research Activity

引き続き、下記の研究項目を設定し本研究課題を遂行する。
項目1：微生物間化学コミュニケーションの解析研究
引き続き、Tsukamurella pulmonis TP-0596と当研究室保有の放線菌ライブラリーの複合培養系を試み、新規化合物生産系を確立し、生産メカニズムや生物活性発現機構の解析等を行う。また、耐熱性放線菌が生産する熱ショック代謝産物（HSM）の生産メカニズムや生物活性発現機構解析等を行う。
項目2：有用生物活性リガンドの開拓研究
引き続き、これまでに見出した有用生物活性リガンドの生合成研究や合成研究を行うとともに、分子プローブ創製研究を行い、細胞内化学シグナルの解析を行う。また、引き続き、がん幹細胞、病原性真菌などを標的として、領域内リソースなどを活用して、有用生物活性リガンドの探索研究を行う。さらに、プロドラッグ型水溶性化合物CMGの希少疾患等における薬効解析などを行う。

Research Products

• [Int'l Joint Research] トロント大学(カナダ)
• [Int'l Joint Research] スイス連邦工科大学(スイス)
• [Int'l Joint Research] プリンストン大学/ジョンズホプキンス(米国)
• [Int'l Joint Research] ライプニッツ天然有機化合物研究所(ドイツ)
• [Int'l Joint Research] トロント大学(カナダ)
• [Int'l Joint Research] スイス連邦工科大学(スイス)
• [Int'l Joint Research] プリンストン大学(米国)
• [Int'l Joint Research] ライプニッツ天然有機化合物研究所(ドイツ)
• [Int'l Joint Research] トロント大学(カナダ)
• [Int'l Joint Research] スイス連邦工科大学(スイス)
• [Int'l Joint Research] プリンストン大学(米国)
• [Int'l Joint Research] ライプニッツ天然有機化合物研究所(ドイツ)
• [Int'l Joint Research] プリンストン大学(米国)
• [Int'l Joint Research] スイス連邦工科大学(スイス)
• [Int'l Joint Research] ライプニッツ天然有機化合物研究所(ドイツ)
• [Journal Article] Amycolapeptins A and B, cyclic nonadepsipeptides produced by combined-culture of Amicolatopsis sp. and Tsukamurella pulmonis (2021)
  • Author(s): Pan, C., Kuranaga, T., Cao, X., Suzuki, T., Dohmae, N., Shinzato, N., Onaka, H., Kakeya, H.
  • Journal Title: The Journal of Organic Chemistry Volume: 86 Pages: 1843-1849
  • DOI: 10.1021/acs.joc.0c02660
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Highly Sensitive Determination of Amino Acids by LC-MS under Neutral Conditions (2021)
  • Author(s): Morimoto, R., Matsumoto, T., Minote, M., Yanagisawa, M., Yamada, R., Kuranaga, T., Kakeya, H.
  • Journal Title: CHEMICAL & PHARMACEUTICAL BULLETIN Volume: 69 Issue: 3 Pages: 265-270
  • DOI: 10.1248/cpb.c20-00958
  • NAID: 130007993065
  • ISSN: 0009-2363, 1347-5223
  • Peer Reviewed
• [Journal Article] Amphiol, an antifungal pigment from Pseudogymnoascus sp. PF1464 (2021)
  • Author(s): Fujita, K., Ikuta, M., Nishimura, S., Sugiyama, R., Yoshimura, A., Kakeya, H.
  • Journal Title: Journal of Natural Products Volume: -
  • DOI: 10.1021/acs.jnatprod.0c01010
  • Peer Reviewed
• [Journal Article] Heterogenous chemosensitivity of organoid cell lines derived from small cell neuroendocrine carcinoma of the uterine cervix (2021)
  • Author(s): Tanaka, M., Kondo, J., Kaneko, K., Endo, H., Onuma, K., Coppo, R., Kamiura, S., Yoshino, K., Ueda, Y., Kakeya, H. Kimura, T., Inoue, M.
  • Journal Title: Human Cell Volume: -
  • DOI: 10.1007/s13577-021-00511-5
  • Peer Reviewed
• [Journal Article] Retro-aza-Michael reaction of an o-aminophenol adduct in protic solvents inspired by natural products (2021)
  • Author(s): Takenaka, K., Kaneko, K., Takahashi, N., Nishimura, S., Kakeya, H.
  • Journal Title: Bioorg. Med. Chem. Volume: -
  • DOI: 10.1016/j.bmc.2021.116059
  • Peer Reviewed
• [Journal Article] Genomic and targeted approachs unveil the cell membrane as a major target of the antifungal cytotoxin amantelide A (2021)
  • Author(s): Elsadek, L.A., Matthews, J.H., Nishimura, S., Nakatani, T., Ito, A., Gu, T., Luo, D., Salvador-Reyes, L.A., Paul, V.J., Kakeya, H., Luesch, H.
  • Journal Title: ChemBioChem Volume: -
  • DOI: 10.1002/cbic.202000685
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Longicatenamides A-D, two diastereomeric pairs of cyclic hexapeptides produced by combined-culture of Streptomyces sp. KUSC_F05 and Tsukamurella pulmonis TP-B0596 (2021)
  • Author(s): Jiang, Y., Matsumoto, T., Kuranaga, T., Lu, S., Wang, W., Onaka, H., Kakeya, H.
  • Journal Title: The Journal of Antibiotics Volume: - Pages: 307-316
  • DOI: 10.1038/s41429-020-00400-3
  • Peer Reviewed
• [Journal Article] Application of the highly sensitive labeling reagent to the structural confirmation of readily isomerizable peptides (2021)
  • Author(s): an, C., Kuranaga, T., Kakeya, H.
  • Journal Title: J. Nat. Med. Volume: 75 Pages: 339-343
  • DOI: 10.1007/s11418-020-01472-z
  • NAID: 40022508940
  • Peer Reviewed
• [Journal Article] The effects of 5-OP-RU stereochemistry on its stability and MAIT-MR1 axis. (2021)
  • Author(s): Matsuoka, T., Motozono, C., Hattori, A., Kakeya, H., Yamasaki, S., Oishi, S., Ohno, H., Inuki, S.
  • Journal Title: ChemBioChem Volume: 22 Pages: 672-678
  • DOI: 10.1002/cbic.202000466
  • Peer Reviewed
• [Journal Article] Highly sensitive labeling reagents for scarce natural products (2020)
  • Author(s): Kuranaga, T., Minote, M., Morimoto, R., Pan, C., Ogawa, H., Kakeya, H
  • Journal Title: ASC Chem. Biol. Volume: 15 Pages: 2499-2506
  • DOI: 10.1021/acschembio.0c00517
  • Peer Reviewed
• [Journal Article] Total synthesis of thioamycolamide A via a biomimetic route (2020)
  • Author(s): Pan, C., Kuranaga, T., Kakeya, H.
  • Journal Title: Org. Biomol. Chem. Volume: 18 Pages: 8366-8370
  • DOI: 10.1039/d0ob01942a
  • Peer Reviewed
• [Journal Article] Miclxin, a novel MIC60 inhibitor, induces apoptosis via mitochondrial stress in β-catenin mutant tumor cells. (2020)
  • Author(s): Ikeda H, Muroi M, Kondoh Y, Ishikawa S, Kakeya H, Osada H, Imoto M
  • Journal Title: ACS Chem. Biol Volume: 15 Pages: 2195-2204
  • DOI: 10.1021/acschembio.0c00381
  • Peer Reviewed / Open Access
• [Journal Article] Methylation deficiency disrupts biological rhythms from bacteria to humans (2020)
  • Author(s): Fustin, J.M., Ye, S., Rakers, C., Kaneko, K., Fukumoto, K., et al., Kakeya, H., Van Ooijen, G., Okamura, H.
  • Journal Title: Commun. Biol. Volume: 3 Pages: 211-211
  • NAID: 120006846495
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] The Synthetic Curcumin Analogue GO-Y030 Effectively Suppresses the Development of Pressure Overload-induced Heart Failure in Mice. (2020)
  • Author(s): Shimizu K, Sunagawa Y, Funamoto M, Wakabayashi H, Genpei M, Miyazaki Y, Katanasaka Y, Sari N, Shimizu S, Katayama A, Shibata H, Iwabuchi Y, Kakeya H, Wada H, Hasegawa K, Morimoto T.
  • Journal Title: Scientific Reports Volume: 10(1) Pages: 7172-7172
  • DOI: 10.1038/s41598-020-64207-w
  • NAID: 120006888478
  • Peer Reviewed / Open Access
• [Journal Article] Curcumin beta-D-glucuronide (CMG) exhibits anti-tumor effects on oxaliplatin-resistant colon cancer with less toxicity (2020)
  • Author(s): Ozawa-Umeta, H., Kishimoto, A., Imaizumi, A., Hashimoto, T., Kakeya, H., Kanai, M.
  • Journal Title: Cancer Sci. Volume: 111 Pages: 1785-1793
  • DOI: 10.1111/cas.14383
  • Peer Reviewed / Open Access
• [Journal Article] Thioamycolamides A-E, Sulfur-Containing Cycliclipopeptides Produced by the Rare Actinomycete Amycolatopsis sp. (2020)
  • Author(s): Chengqian Pan, Takefumi Kuranaga, Chao Liu, Shan Lu, Naoya Shinzato, Hideaki Kakeya
  • Journal Title: Org. Lett. Volume: 22 Pages: 3014-3017
  • DOI: 10.1021/acs.orglett.0c00776
  • Peer Reviewed
• [Journal Article] Serinr catabolism produce ROS, sensitizes cells to actin dysfunction, and suppresses cell growth in fission yeast. (2020)
  • Author(s): Kanou, A., Nishimura, S., Tabuchi, T., Matsuyama, A., Yoshida, M., Kato, T., Kakeya, H.
  • Journal Title: J. Antibiot (Tokyo) Volume: 73 Pages: 574-580
  • DOI: 10.1038/s41429-020-0305-6
  • Peer Reviewed
• [Journal Article] Different localization of lysosomal-associated membrane protein 1 (LAMP1) in mammalian cultured cell lines (2020)
  • Author(s): Kosuke Baba, Sara Kuwada, Ayaka Nakao, Xuebing Li, Naoaki Okuda, Ai Nishida, Satoshi Mitsuda, Natsuki Fukuoka, Hideaki Kakeya, Takao Kataoka
  • Journal Title: Histochem. Cell. Biol. Volume: 153 Pages: 199-213
  • DOI: 10.1007/s00418-019-01842-z
  • Peer Reviewed
• [Journal Article] A chemical genomics-aggrephagy integrated method studying functional analysis of autophagy inducers. (2020)
  • Author(s): Kataura T, Tashiro E, Nishikawa S, Onodera M, Shin-ya K, et al, Sasazawa Y, Hattori N, Saiki S, and Imoto M
  • Journal Title: Autophagy Volume: Aug 7 Pages: 1-17
  • DOI: 10.1080/15548627.2020.1794590
  • Description: in press
  • Peer Reviewed / Open Access
• [Journal Article] BRUP-1, an intracellular bilirubin modulator, exerts neuroprotective activity in a cellular Parkinson's disease model. (2020)
  • Author(s): Kataura T, Saiki S, Ishikawa K, Akamatsu W, Sasazawa Y, Hattori N, Imoto M
  • Journal Title: J Neurochem Volume: － Pages: 81-97
  • DOI: 10.1111/jnc.14997
  • Description: in press
  • Peer Reviewed / Open Access
• [Journal Article] Discovery of “heat shock metabolites” produced by thermotolerant actinomycetes in high-temperature culture (2020)
  • Author(s): Saito S, Kato W, Ikeda H, Katsuyama Y, *Ohnishi Y, *Imoto M.
  • Journal Title: J. Antibiotics Volume: 73 Pages: 203-210
  • DOI: 10.1038/s41429-020-0279-4
  • Peer Reviewed / Open Access
• [Journal Article] Total synthesis and antimicrobial activity of tumescenamide C and its derivatives. (2020)
  • Author(s): Takahashi, N., Kaneko, K., Kakeya, H.
  • Journal Title: J. Org. Chem. Volume: 85 Pages: 4530-4535
  • DOI: 10.1021/acs.joc.9b03516
  • Peer Reviewed
• [Journal Article] Ubiquitin carboxyl‐terminal hydrolase L1 promotes hypoxia‐inducible factor 1‐dependent tumor cell malignancy in spheroid models (2020)
  • Author(s): Li Xuebing、Hattori Akira、Takahashi Senye、Goto Yoko、Harada Hiroshi、Kakeya Hideaki
  • Journal Title: Cancer Sci. Volume: 111 Pages: 239-252
  • DOI: 10.1111/cas.14236
  • NAID: 120006848248
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Cryptic chemical communication: Secondary metabolic responses revealed by microbial co-culture. (2020)
  • Author(s): Liu, C., Kakeya, H.
  • Journal Title: Chem. Asian. J. Volume: 15 Pages: 327-337
  • DOI: 10.1002/asia.201901505
  • Peer Reviewed
• [Journal Article] Total synthesis of verucopeptin, an inhibitor of hypoxia-inducible factor 1 (HIF-1). (2019)
  • Author(s): Takahashi, N., Hayashi, H., Poznaks, V., Kakeya, H.
  • Journal Title: Chem. Commun. Volume: 55 Pages: 11956-11959
  • DOI: 10.1039/c9cc06169j
  • Peer Reviewed
• [Journal Article] Isolation, Structure Elucidation, and Conformational Regulation of Myropeptins, Lipopeptides from the Fungus Myrothecium roridum. (2019)
  • Author(s): Yoshimura, A., Nishimura, S.*, Suzuki, T., Hattori, A., Dohmae, N., Kato, T. & Kakeya, H.
  • Journal Title: Org. Lett. Volume: 21 Pages: 7524-7528
  • DOI: 10.1021/acs.orglett.9b02801
  • Peer Reviewed
• [Journal Article] Chemical Interactions of Cryptic Actinomycete Metabolite 5‐Alkyl‐1,2,3,4‐tetrahydroquinolines through Aggregate Formation (2019)
  • Author(s): Sugiyama Ryosuke、Nakatani Takahiro、Nishimura Shinichi、Takenaka Kei、Ozaki Taro、Asamizu Shumpei、Onaka Hiroyasu、Kakeya Hideaki
  • Journal Title: Angew. Chem. Int. Ed. Volume: 58 Pages: 13486-13491
  • DOI: 10.1002/anie.201905970
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Effects of Highly Absorbable Curcumin in Patients with Impaired Glucose Tolerance and Non-Insulin-Dependent Diabetes Mellitus (2019)
  • Author(s): Funamoto Masafumi、Shimizu Kana、Sunagawa Yoichi、Katanasaka Yasufumi、Miyazaki Yusuke、Kakeya Hideaki、Yamakage Hajime、Satoh-Asahara Noriko、Wada Hiromichi、Hasegawa Koji、Morimoto Tatsuya
  • Journal Title: J. Diabetes Res. Volume: 2019 Pages: 1-7
  • DOI: 10.1155/2019/8208237
  • NAID: 120006888005
  • Peer Reviewed / Open Access
• [Journal Article] Identification of the common biosynthetic gene cluster for both antimicrobial streptoaminals and antifungal 5-alkyl-1,2,3,4-tetrahydroquinolines (2019)
  • Author(s): Ozaki Taro、Sugiyama Ryosuke、Shimomura Morito、Nishimura Shinichi、Asamizu Shumpei、Katsuyama Yohei、Kakeya Hideaki、Onaka Hiroyasu
  • Journal Title: Org. Biomol. Chem. Volume: 17 Pages: 2370-2378
  • DOI: 10.1039/c8ob02846j
  • Peer Reviewed
• [Journal Article] Enhancement of saccharothriolide production and discovery of a new metabolite, saccharothriolide C2, by combined-culture of Saccharothrix sp. and Tsukamurella pulmonis (2019)
  • Author(s): Yulu Jiang, Shan Lu, Go Hirai, Taira Kato, Hiroyasu Onaka, Hideaki Kakeya
  • Journal Title: Tetrahedron Letters Volume: 60 Pages: 1072-1074
  • DOI: 10.1016/j.tetlet.2019.03.034
  • Peer Reviewed
• [Journal Article] Theonellamide A, a marine-sponge-derived bicyclic peptide, binds to cholesterol in aqueous DMSO: Solution NMR-based analysis of peptide-sterol interactions using hydroxylated sterol (2019)
  • Author(s): Cornelio Kimberly、Espiritu Rafael Atillo、Hanashima Shinya、Todokoro Yasuto、Malabed Raymond、Kinoshita Masanao、Matsumori Nobuaki、Murata Michio、Nishimura Shinichi、Kakeya Hideaki、Yoshida Minoru、Matsunaga Shigeki
  • Journal Title: Biochim. Biophys. Acta Biomembr. Volume: 1861 Pages: 228-235
  • DOI: 10.1016/j.bbamem.2018.07.010
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Development of an anti-hepatitisB virus (HBV) agent through the structure-activity relationship of theinterferon-like small compound CDM-3008 (2019)
  • Author(s): Nobuaki Takahashi, Kyohei Hayashi, Yusuke Nakagawa, Yutaka Furutani, Mariko Toguchi, Yumi Shiozaki-Sato, Masayuki Sudoh, Soichi Kojima, Hideaki Kakeya
  • Journal Title: 10.1016/j.bmc.2018.11.039 Volume: 27 Pages: 470-478
  • Peer Reviewed
• [Journal Article] 研究トピックス：がんと宿主の化学コミュニケーション阻害を指向した水溶性プロドラッグ型抗がん剤CMGの開発研究 (2019)
  • Author(s): 掛谷秀昭
  • Journal Title: 新学術領域研究「化学コミュニケーションのフロンティア」・Newsletter Volume: 3 Pages: 10-10
• [Journal Article] 研究トピックス：微生物間化学コミュニケーションの利活用によるケミカルスペース拡充戦略 (2019)
  • Author(s): 掛谷秀昭
  • Journal Title: 新学術領域研究「化学コミュニケーションのフロンティア」・Newsletter Volume: 3 Pages: 9-9
• [Journal Article] CAPZA1 determines the risk of gastric carcinogenesis by inhibiting Helicobacter pylori CagA-degraded autophagy (2019)
  • Author(s): Tsugawa H., Mori H., Matsuzaki J., Sato A., Saito Y., Imoto M., Suematsu M., Suzuki H.
  • Journal Title: Autophagy. Volume: 15 Pages: 1-17
  • DOI: 10.1080/15548627.2018.1515530
  • Peer Reviewed / Open Access
• [Journal Article] 天然物スクリーニングによる制がん剤シードの探索研究 (2019)
  • Author(s): 井本正哉
  • Journal Title: The Japanese Journal of Antibiotics Volume: 72 Pages: 15-22
  • NAID: 40021853597
  • Peer Reviewed
• [Journal Article] Natural products-inspired chemical biology toward developmentof new antibiotics (2018)
  • Author(s): Hideaki Kakeya
  • Journal Title: Jpn. J. Antibiot. Volume: 71 Pages: 181-191
  • Peer Reviewed
• [Journal Article] Discovery of presaccharothriolide X, a retro-Michael product of saccharothriolide B, from the rare actinomycete Saccharothrix sp. A1506 (2018)
  • Author(s): Shan Lu, Shinichi Nishimura, Kei Takenaka, Masashi Ito, Taira Kato, Hideaki Kakeya
  • Journal Title: Org. Lett. Volume: 20 Pages: 4406-4410
  • DOI: 10.1021/acs.orglett.8b01535
  • Peer Reviewed
• [Journal Article] Curcumin and its demethoxy derivatives possess p300HAT inhibitory activity and suppress hypertrophic response in cardiomyocytes (2018)
  • Author(s): Yoichi Sunagawa, Masafumi Funamoto, Shogo Sono, Kana Shimizu, Satoshi Shimizu, Mai Genpei, Yusuke Miyazaki, Yasufumi Katanasaka, Eriko Morimoto, Morio Ueno, Maki Komiyama, Hideaki Kakeya, Hiromichi Wada, Koji Hasegawa, Tasuya Morimoto
  • Journal Title: J. Pharmacol. Sci. Volume: 136 Pages: 212-217
  • DOI: 10.1016/j.jphs.2017.12.013
  • NAID: 120006501305
  • Peer Reviewed / Open Access
• [Journal Article] Activity-Based Protein Profiling of Non-ribosomal Peptide Synthetases (2018)
  • Author(s): Ishikawa Fumihiro、Tanabe Genzoh、Kakeya Hideaki
  • Journal Title: Curr. Top. Microbiol. Immunol. Volume: 420 Pages: 321-349
  • DOI: 10.1007/82_2018_133
  • Peer Reviewed
• [Journal Article] 生体膜を標的にする天然有機化合物：天然物による厳密な脂質認識とそれに基づく表現型 (2018)
  • Author(s): 西村慎一, 掛谷秀昭, 松森信明
  • Journal Title: 化学と生物 Volume: 56 Pages: 678-685
  • NAID: 130007709540
  • Peer Reviewed
• [Journal Article] 14-3-3εa directs the pulsatile transport of basal factors towards the apical domain for lumen growth in tubulogenesis. (2018)
  • Author(s): Yuji Mizotani, Mayu Suzuki, Kohji Hotta, Hidenori Watanabe, Kogiku Shiba, Kazuo Inaba, Etsu Tashiro, Kotaro Oka, Masaya Imoto
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: 115
  • DOI: 10.1073/pnas.1808756115
  • NAID: 120007133686
  • Peer Reviewed / Open Access
• [Journal Article] Chemistry and biology for the small molecules targeting characteristics of cancer cells (2018)
  • Author(s): Masaya Imoto
  • Journal Title: Biosci Biotechnol Biochem Volume: 83 Pages: 1-10
  • DOI: 10.1080/09168451.2018.1518704
  • Peer Reviewed
• [Journal Article] 天然物スクリーニングとケミカルバイオロジーへの展開 (2018)
  • Author(s): 井本正哉
  • Journal Title: 化学と生物 Volume: 56 Pages: 203-208
  • NAID: 130007602188
  • Peer Reviewed
• [Journal Article] Curcumin β-D-Glucuronide Plays an Important Role to Keep High Levels of Free-Form Curcumin in the Blood (2017)
  • Author(s): Ozawa, H., Imaizumi, A., Sumi, Y., Hashimoto, T., Kanai, M., Makino, Y., Tsuda, T., Takahashi, N., Kakeya, H.
  • Journal Title: Biol. Pharm. Bull. Volume: 40 Issue: 9 Pages: 1515-1524
  • DOI: 10.1248/bpb.b17-00339
  • NAID: 130006038773
  • ISSN: 0918-6158, 1347-5215
  • Peer Reviewed / Open Access
• [Journal Article] Visualizing the adenylation activities and protein-protein interactions of aryl acid adenylating enzymes (2017)
  • Author(s): Ishikawa, F., Kasai, S., Kakeya, H., Tanabe, G.
  • Journal Title: ChemBioChem. Volume: 18 Pages: 2199-2204
  • DOI: 10.1002/cbic.201700361
  • Peer Reviewed
• [Journal Article] A chemoproteomics platform to investigate phosphopantetheine transferase activity at the cellular level (2017)
  • Author(s): Konno, S., Ishikawa, F., Suzuki, T., Dohmae, N., Kakeya, H., Tanabe, G.
  • Journal Title: ChemBioChem. Volume: 18 Pages: 1855-1862
  • DOI: 10.1002/cbic.201700301
  • Peer Reviewed
• [Journal Article] Precursor-directed in situ synthesis of saccharothriolides G and H by the actinomycete Saccharothrix sp. (2017)
  • Author(s): Shan Lu, Shinich Nishimura, Masashi Ito, Taira Kato, Hideaki Kakeya
  • Journal Title: J. Antibiot. Volume: 70 Pages: 718-720
  • DOI: 10.1038/ja.2016.153
  • Peer Reviewed
• [Presentation] ピラゾール骨格を有する新規低酸素誘導因子HIF-1阻害剤の開発研究 (2021)
  • Author(s): 酒井麻利奈, 高橋伸明, 古谷 裕, 鈴木健裕, 堂前 直, 小林清香, 服部 明, 原田 浩, 掛谷秀昭
  • Organizer: 日本薬学会第141年会
• [Presentation] がん幹細胞を標的とした抗がん剤シーズ探索系の構築 (2021)
  • Author(s): 池田拓慧, 川見美里, 井本正哉, 掛谷秀昭
  • Organizer: 日本薬学会第141年会
• [Presentation] 自然に学ぶ生理化学研究：分子プローブ開発と創薬 (2020)
  • Author(s): 掛谷秀昭
  • Organizer: 京都大学学際融合教育推進センター・生理化学研究ユニット第10回公開シンポジウム
  • Invited
• [Presentation] Discovery of sulfur-containing cyclic lipopeptides thioamycolamides A-E, producedby the rare ctinomycete Amycolatopsis sp. (2020)
  • Author(s): Pan, C., Kuranaga, T., Liu, C., Lu, S., Shinzato, N., Kakeya, H
  • Organizer: The 62nd Symposium on the Chemistry of Natural Products
• [Presentation] 希少天然物の構造をモチーフとした高感度ラベル化剤の開発 (2020)
  • Author(s): 箕手万由里, 小川はるか, 森本涼太, 潘 承謙, 倉永健史, 掛谷秀昭
  • Organizer: 日本薬学会第140年会
• [Presentation] アカデミア発創薬を目指した創薬ケミカルバイオロジー研究 (2020)
  • Author(s): 掛谷秀昭
  • Organizer: TSMTP (Translational Science and MedicineTraining Program) Symposium in Sapporo
  • Invited
• [Presentation] 有用生物活性リガンドの開発を志向した化学コミュニケーション研究 (2020)
  • Author(s): 掛谷秀昭
  • Organizer: 有機合成のニュートレンド2020（有機合成化学協会関西支部主催）
  • Invited
• [Presentation] Continuing Fascination with Discovery Science: Phenotypic Screening to Chemical Biology (2020)
  • Author(s): Kakeya, H.
  • Organizer: Mona Symposium 2020: Natural Product Chemistry and Medicinal Chemistry
  • Int'l Joint Research / Invited
• [Presentation] 微生物間化学コミュニケーションの理解と有用生物活性リガンドの開発 (2019)
  • Author(s): 掛谷秀昭
  • Organizer: 新学術領域研究「化学コミュニケーションのフロンティア」・第6回公開シンポジウム
  • Invited
• [Presentation] Chemical comunication research toward the development of usefulchemical probes (2019)
  • Author(s): Kakeya, H.
  • Organizer: The 4th A3 Roundtable Meeting on Asia Chemical Probe Research
  • Int'l Joint Research / Invited
• [Presentation] Natural products-prompted chemical biology: Phenotypic screeningand a new platform for target identification (2019)
  • Author(s): Kakeya, H.
  • Organizer: The 6th Tishler-Omura Sympoium
  • Int'l Joint Research / Invited
• [Presentation] Developmentof an injectable water-soluble anticancer drug CMG for oxaliplatin-resistantcolorectal cancer with KRAS mutation (2019)
  • Author(s): Kakeya, H, Kishimoto, A., Umeta, H., Imaizumi, A., Kanai, M.
  • Organizer: 31th EORTC-NCI-AACR Symposium: InternationalConference on Molecular Targets and Cancer Therapeutics
  • Int'l Joint Research
• [Presentation] Highly sensitive labeling reagents inspired bya scarce marine natural product (2019)
  • Author(s): Kuranaga, T., Kakeya, H.
  • Organizer: 10th Korea-Japan Chemical Biology Symposium
  • Int'l Joint Research / Invited
• [Presentation] Symposia20 "Frontier in Molecular Target Therapy of Cancer": Developmentof a water-soluble prodrug CMG which inhibits proteasome activity throughDYRK2 dependent manner. (2019)
  • Author(s): Kanai, M., Kishimoto, A., Umeta, H., Imaizumi, A., Kakeya, H.
  • Organizer: The 78th Annual Meeting of the Japanese CancerAssociation
  • Int'l Joint Research / Invited
• [Presentation] 低酸素誘導因子HIF-1阻害活性を有する環状デプシペプチドverucopeptinの全合成 (2019)
  • Author(s): 高橋伸明, 林 秀明, Poznaks, V. 掛谷秀昭
  • Organizer: 第61回天然有機化合物討論会
• [Presentation] Frontier research on chemical communications unveils the mysteryof life science (2019)
  • Author(s): Kakeya, H.
  • Organizer: The 27th International Society of Heterocyclic ChemistryCongress
  • Int'l Joint Research / Invited
• [Presentation] 自然に学ぶ薬づくり (2019)
  • Author(s): 掛谷秀昭, 倉永健史
  • Organizer: 京都大学アカデミックデイ2019
• [Presentation] 微生物間化学コミュニケーションの利活用による新規生物活性リガンドの開発研究 (2019)
  • Author(s): 掛谷秀昭
  • Organizer: 第19回日本蛋白質科学会年会・第71回日本細胞生物学会大会合同年次大会
  • Invited
• [Presentation] 「シンポジウム・がんと宿主の化学コミュニケーションの理解と制御」. 水溶性プロドラッグ型分子標的抗がん剤CMGの開発研究 (2019)
  • Author(s): 掛谷秀昭
  • Organizer: 第23回日本がん分子標的治療学会学術集会
  • Invited
• [Presentation] 低酸素応答シグナルを標的とした創薬ケミカルバイオロジー (2019)
  • Author(s): 掛谷秀昭
  • Organizer: 日本薬学会第139年会（千葉）
  • Invited
• [Presentation] 化学コミュニケーションが織りなす生命科学 (2019)
  • Author(s): 掛谷秀昭
  • Organizer: 日本化学会第99春季年会（2019, 神戸）
  • Invited
• [Presentation] Development of cryptic antifungal 5aTHQs targeting cell membranesignaling (2019)
  • Author(s): Hideaki Kakeya
  • Organizer: Asian Chemical Biology Initiative (ACBI) 2019 Yangon Meeting
  • Int'l Joint Research / Invited
• [Presentation] 天然物創薬の復権を期して：微生物間化学コミュニケーションの利活用 (2019)
  • Author(s): 掛谷秀昭
  • Organizer: 第402回CBI学会（情報計算化学生物学会）講演会（東京）
  • Invited
• [Presentation] Developmentof an innovative water-soluble anticancer drug, curcumin mono-beta-D-glucuronide(CMG) (2019)
  • Author(s): Hideaki Kakeya, Nobuaki Takahashi, Atsuhiro Kishimoto, Atsushi Imaizumi, Masashi Kanai
  • Organizer: The 1st International Symposium on Chemical Communication (ISCC2019, Tokyo)
  • Int'l Joint Research
• [Presentation] Towards thedevelopment of chemical communication molecules among microbes. (2019)
  • Author(s): Yulu Jiang, Shan Lu, Go Hirai, Taira Kato, Hiroyasu Onaka, Hideaki Kakeya
  • Organizer: The 1st International Symposium on Chemical Communication (ISCC2019, Tokyo)
  • Int'l Joint Research
• [Presentation] ホヤ脊索管形成の制御機構のケミカルバイオロジー (2019)
  • Author(s): 井本正哉
  • Organizer: 日本農芸化学会 2019年度大会（東京）
  • Invited
• [Presentation] Rapid screening of antibody-bindingpeptides by combination of T7 phage display and next-generation sequencingtechnologies (2018)
  • Author(s): Motohiro Nonaka, Michiko Fukuda, Hideaki Kakeya
  • Organizer: The 1st International Symposium on Chemical Communication (ISCC2019, Tokyo)
  • Int'l Joint Research
• [Presentation] Development of a syntheticwater-soluble curcumin mono-beta-D-glucuronide (CMG), as an innovativeanticancer prodrug targeting KRAS-NF-kappaB signaling pathway (2018)
  • Author(s): Hideaki Kakeya, Atsuhiro Kishimoto, Atsushi Imaizumi, Masashi Kanai
  • Organizer: 30th EORTC-NCI-AACRSymposium: International Conference on Molecular Targets and Cancer Therapeutics (Dublin)
  • Int'l Joint Research
• [Presentation] Drug delivery to malignant brain tumorby a peptide specific to Annexin A1 (2018)
  • Author(s): Motohiro Nonaka, Hideaki Kakeya, Michiko Fukuda.
  • Organizer: 30th EORTC-NCI-AACRSymposium: International Conference on Molecular Targets and Cancer Therapeutics (Dublin)
  • Int'l Joint Research
• [Presentation] 医薬品シード分子の多様性創出と細胞内標的探索・同定 (2018)
  • Author(s): 掛谷秀昭
  • Organizer: 京大テックフォーラム（東京）
  • Invited
• [Presentation] 微生物の複合培養で得られる5aTHQの膜親和性と生物活性. 第60回天然有機化合物討論会 (2018)
  • Author(s): 西村慎一, 杉山龍介, 仲谷崇宏, 尾崎太郎, 浅水俊平, 尾仲宏康, 掛谷秀昭
  • Organizer: 第60回天然有機化合物討論会（福岡）
• [Presentation] アポトーシス誘導活性天然物cytotrieninAの合成研究 (2018)
  • Author(s): 岩渕好治, 佐藤亮, 笹野裕介, 小松慎吾, 野口正嗣, 掛谷秀昭, 長田裕之, 叶直樹
  • Organizer: 第60回天然有機化合物討論会（福岡）
• [Presentation] 天然物創薬ケミカルバイオロジー (2018)
  • Author(s): 掛谷秀昭, 野中元裕, 倉永健史
  • Organizer: 京都大学アカデミックデイ2018
• [Presentation] 多隔壁形成や細胞伸長におけるスフィンゴ脂質の重要性 (2018)
  • Author(s): 生田実沙, 伊藤愛理, 西村慎一, 吉田 稔, 掛谷秀昭
  • Organizer: 酵母遺伝学フォーーラム第51回研究報告会（福岡）
• [Presentation] 天然物創薬ケミカルバイオロジーの醍醐味 (2018)
  • Author(s): 掛谷秀昭
  • Organizer: 第53回天然物化学談話会（大阪）
  • Invited
• [Presentation] 微生物間化学コミュニケーションの理解と有用生物活性リガンドの開発 (2018)
  • Author(s): 掛谷秀昭, 西村慎一, 倉永健史, 野中元裕, 井本正哉
  • Organizer: 新学術領域研究「化学コミュニケーションのフロンティア」・第3回公開シンポジウム（東京）
• [Presentation] 「化学コミュニケーションのフロンティア」を起点にした創薬ケミカルバイオロジー (2018)
  • Author(s): 掛谷秀昭
  • Organizer: 新学術領域研究「脂質クオリティが解き明かす生命現象」第4回領域会議
  • Invited
• [Presentation] Microbial metabolites targeting microenvironment: a cell membranesigaling modulator and a hypoxia-response modulator (2018)
  • Author(s): Hideaki Kakeya
  • Organizer: The 9th Japan-Koreachemical biology symposium (Inchon, Korea)
  • Int'l Joint Research / Invited
• [Presentation] Development of a water-soluble curcuminmonoglucronide (CMG) as a novel anticancer prodrug targeting KRAS-NF-kappaB signaling pathway (2018)
  • Author(s): Kanai, M., Imaizumi, A., Kakeya, H
  • Organizer: Global Academic Programs (GAP) conference (Stockholm, Sweden)
  • Int'l Joint Research
• [Presentation] がん細胞の特性を標的とする阻害剤の化学生物学的研究 (2018)
  • Author(s): 井本正哉
  • Organizer: 日本農芸化学会 2018年度第1回 関東支部例会（神奈川）
  • Invited
• [Presentation] ホヤ脊索管形成機構に挑むケミカルバイオロジー (2018)
  • Author(s): 井本正哉
  • Organizer: （独）日本学術振興会 産学協力研究委員会第170委員会・第189委員会 合同シンポジウム （東京）
  • Invited
• [Presentation] Expansion of chemical space in saccharothriolides: Precursor-directed in situ synthesis (PDSS) in a rare actinomycete Saccharothrix sp (2018)
  • Author(s): Shan Lu, Shinichi Nishimura, Masashi Ito, Taira Kato, Hideaki Kakeya
  • Organizer: Natural Product Discovey & Development in the Genomic Era (Natural Products 2018)
  • Int'l Joint Research
• [Presentation] 微生物間化学コミュニケーションの利活用によるケミカルスペース拡充戦略 (2018)
  • Author(s): 掛谷秀昭
  • Organizer: 新学術領域研究「化学コミュニケーションのフロンティア」・第2回公開シンポジウム
  • Invited
• [Presentation] 「シンポジウム：これからの天然物サイエンス」―ケミカルスペース拡充戦略：微生物複合培養法及びPDSS (Precurso-Directed in situ Synthesis)法― (2018)
  • Author(s): 掛谷秀昭
  • Organizer: 日本農芸化学会2018年度大会
  • Invited
• [Presentation] 「中長期企画・ケミカルバイオロジー研究加速のための生物活性分子の発見戦略」―微生物間化学コミュニケーションの謎に挑む― (2018)
  • Author(s): 掛谷秀昭
  • Organizer: 日本化学会第98春季年会（2018）
  • Invited
• [Presentation] 機能性食品素材の医薬品への展開を目指した創薬ケミカルバイオロジー (2017)
  • Author(s): 今泉 厚, 高橋伸明, 光金英宣, 金井雅史, 橋本 正, 牧野悠治, 津田孝範, 掛谷秀昭
  • Organizer: 第7回食品薬学シンポジウム
  • Invited
• [Presentation] 創農薬イノベーションを創発するケミカルバイオロジー方略 (2017)
  • Author(s): 掛谷秀昭
  • Organizer: 農薬デザイン研究会
  • Invited
• [Presentation] 謎解きと宝探しの天然物ケミカルバイオロジー (2017)
  • Author(s): 井本正哉
  • Organizer: 第52回天然物化学談話会
  • Invited
• [Presentation] Synthetic lethal killing of β-catenin mutant cancer cells by small molecules (2017)
  • Author(s): Masaya Imoto
  • Organizer: 3rd KRIBB-RIKEN Chemical Biology Joint Symposium
  • Int'l Joint Research
• [Presentation] βカテニン変異がん細胞に合成致死を誘導する化合物の探索 (2017)
  • Author(s): 井本正哉
  • Organizer: 第76回日本癌学会学術総会
  • Invited
• [Book] くすりの科学知識（増補第2版） (2019)
  • Author(s): 掛谷秀昭
  • Total Pages: 175
  • Publisher: ニュートンプレス
  • ISBN: 9784315521894
• [Book] ケミカルバイオロジー化合物集 (2018)
  • Author(s): 日本におけるケミカルバイオロジーの新展開第189委員会
  • Total Pages: 304
  • Publisher: オーム社
  • ISBN: 9784274507090
• [Book] 1. 薬の基礎知識 & 2. 創薬の世界, Newton 別冊 「くすりの科学知識：くすりのしくみと、奥深き創薬の世界」 (2017)
  • Author(s): 掛谷秀昭（監修）
  • Total Pages: 144
  • Publisher: ニュートンプレス社
  • ISBN: 9784315520835
• [Remarks] 京都大学大学院薬学研究科 医薬創成情報科学専攻 システムケモセラピー（制御分子学）分野
  • URL: https://www.pharm.kyoto-u.ac.jp/sc-molsci/
• [Remarks] 京都大学大学院薬学研究科 医薬創成情報科学専攻 システムケモセラピー（制御分子学）分野
  • URL: http://www.pharm.kyoto-u.ac.jp/sc-molsci/
• [Remarks] 京都大学大学院薬学研究科 医薬創成情報科学専攻 システムケモセラピー（制御分子学）分野
  • URL: http://www.pharm.kyoto-u.ac.jp/sc-molsci/
• [Patent(Industrial Property Rights)] 含窒素複素環式化合物 (2020)
  • Inventor(s): 掛谷秀昭, 酒井麻利奈, 古谷 裕
  • Industrial Property Rights Holder: 掛谷秀昭, 酒井麻利奈, 古谷 裕
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2020-209649
  • Filing Date: 2020
• [Patent(Industrial Property Rights)] 新規フルオロジニトロフェニル化合物及びその用途 (2019)
  • Inventor(s): 掛谷秀昭、倉永健史、小川はるか
  • Industrial Property Rights Holder: 掛谷秀昭、倉永健史、小川はるか
  • Industrial Property Rights Type: 特許
  • Filing Date: 2019