研究者基本情報

• https://researchmap.jp/tmanome

• https://orcid.org/0000-0001-5511-2331
• https://jglobal.jst.go.jp/detail?JGLOBAL_ID=202401015881118095

• https://orcid.org/0000-0001-5511-2331

• 202401015881118095

• 二次代謝産物
• 天然物化学

• ライフサイエンス, 生物有機化学, 天然物化学
• ライフサイエンス, 環境、天然医薬資源学

研究活動情報

• 2024年10月, 食品薬学シンポジウム, 優秀発表賞
  細胞外膜小胞が有する天然物生産誘導能の一般性の検証
• 2024年03月, 日本薬学会, 学生優秀発表賞
  多様な細菌種由来の細胞外膜小胞を用いた新規天然物探索
• 2023年03月, 日本薬学会, 学生優秀発表賞
  放線菌Nocardia carnea IFM12324からの新規天然物の探索と生合成遺伝子解析
• 2022年09月, 日本生薬学会, 優秀発表賞
  Physalis minimaからの新規physalin探索とそのTRAIL耐性克服作用の作用機序解析

• Stigmatellamines A-D: Bacterial Membrane Vesicle-Induced N-Alkylpyridinium Alkaloids from Stigmatella aurantiaca.
  Teruhisa Manome; Aya Yoshimura; Keiko Konuma; Yui Numata; Kumi Kawaji; Eiichi N Kodama; Toshiyuki Wakimoto
  Journal of natural products, 2026年04月15日, ［査読有り］, ［筆頭著者］, ［国際誌］
  英語, 研究論文（学術雑誌）, Four N-alkylpyridinium alkaloids, stigmatellamines A-D (1-4), were isolated from Stigmatella aurantiaca as metabolites induced by membrane vesicles derived from Burkholderia plantarii. Their chemical structures were elucidated through a combination of spectroscopic and synthetic approaches, revealing a unique class of tetrasubstituted N-alkylpyridinium alkaloids. Stigmatellamines A-C exhibited potent cytotoxicity against the human B-cell lymphocytes, RPMI8226. This is the first evidence supporting the ability of B. plantarii MVs to induce cryptic metabolite biosynthesis.
• A new diterpenoid, carneadiol, isolated from Nocardia carnea IFM 12324.
  Yasumasa Hara; Ayaka Nakamura; Teruhisa Manome; Akiko Takaya; Hiroki Takahashi; Sayaka Ban; Takashi Yaguchi; Masami Ishibashi
  Journal of natural medicines, 79, 2, 435, 440, 2025年03月, ［査読有り］, ［国内誌］
  英語, 研究論文（学術雑誌）, A new diterpenoid, carneadiol (1), with an unprecedented tricyclic carbon skeleton, was isolated from the culture extracts of Nocardia carnea IFM 12324. The structure of compound 1 was elucidated using spectral studies, including various NMR data. The absolute configuration of 1 was determined using X-ray crystallographic analysis with the crystalline sponge method. The biosynthetic gene of compound 1 was deduced, and it was observed that the mRNA of the gene involved in terpenoid cyclization increased significantly in the strain producing compound 1.
• Isolation of bioactive phytochemicals from Crinum asiaticum L. along with their cytotoxic and TRAIL-resistance abrogating prospect assessment.
  Sharmin Ahmed Rakhi; Yasumasa Hara; Md Saiful Islam; Teruhisa Manome; Safaet Alam; Nazim Uddin Emon; Muhammad Abdullah Al-Mansur; Md Ruhul Kuddus; Md Raihan Sarkar; Masami Ishibashi; Firoj Ahmed
  Heliyon, 10, 3, e25049, 2024年02月15日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Crinum asiaticum L. (Amaryllidaceae) is a perennial bulbous herb, locally utilized for possessing multifaceted pharmacological properties including anticancer, immune-stimulating, analgesic, antiviral, antimalarial, antibacterial and antifungal, in addition to its popularity as an aesthetic plant. Separation of MeOH extract of C. asiaticum leaves yielded three known compounds as cycloneolitsol (1), hippeastrine (2) and β-sitosterol (3). Among these, compounds 1 and 2 were subjected to the cytotoxic assay and found that they induced mild effect against HCT116, Huh7 and DU145 cell lines with the IC50 values from 73.76 to 132.53 μM. When tested for TRAIL-resistance abrogating activity, 1 (100 μM) along with TRAIL (100 ng/mL) showed moderate activity in AGS cells producing 25 % more inhibition than the agent alone. Whereas 2 (20 and 30 μM) in combination with TRAIL (100 ng/mL) exhibited strong activity in abrogating TRAIL-resistance and caused 34 % and 36 % more inhibition in AGS cells, respectively. The in-silico studies of compound 2 revealed high docking hits with the TRAIL-associated anti-apoptotic proteins which give a justification for the regulatory interactions to induce such abrogating activity. It is still recommended to conduct further investigations to understand their exact molecular mechanism.
• Physalin H, physalin B, and isophysalin B suppress the quorum-sensing function of Staphylococcus aureus by binding to AgrA.
  Junpei Yamaguchi; Teruhisa Manome; Yasumasa Hara; Yuriko Yamazaki; Yuumi Nakamura; Masami Ishibashi; Akiko Takaya
  Frontiers in pharmacology, 15, 1365815, 1365815, 2024年, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, The virulence of Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), depends on the expression of toxins and virulence factors controlled by the quorum-sensing (QS) system, encoded on the virulence accessory gene regulator (agr) locus. The aim of this study was to identify a phytochemical that inhibits Agr-QS function and to elucidate its mechanism. We screened 577 compounds and identified physalin H, physalin B, and isophysalin B--phytochemicals belonging to physalins found in plants of the Solanaceae family--as novel Agr-QS modulators. Biological analyses and in vitro protein-DNA binding assays suggested that these physalins suppress gene expression related to the Agr-QS system by inhibiting binding of the key response regulator AgrA to the agr promoters, reducing the function of hemolytic toxins downstream of these genes in MRSA. Furthermore, although physalin F suppressed gene expression in the Agr-QS system, its anti-hemolytic activity was lower than that of physalins H, B, and isophysalin B. Conversely, five physalins isolated from the same plant with the ability to suppress Agr-QS did not reduce bacterial Agr-QS activity but inhibited AgrA binding to DNA in vitro. A docking simulation revealed that physalin interacts with the DNA-binding site of AgrA in three docking states. The carbonyl oxygens at C-1 and C-18 of physalins, which can suppress Agr-QS, were directed to residues N201 and R198 of AgrA, respectively, whereas these carbonyl oxygens of physalins, without Agr-QS suppression activity, were oriented in different directions. Next, 100-ns molecular dynamics simulations revealed that the hydrogen bond formed between the carbonyl oxygen at C-15 of physalins and L186 of AgrA functions as an anchor, sustaining the interaction between the carbonyl oxygen at C-1 of physalins and N201 of AgrA. Thus, these results suggest that physalin H, physalin B, and isophysalin B inhibit the interaction of AgrA with the agr promoters by binding to the DNA-binding site of AgrA, suppressing the Agr-QS function of S. aureus. Physalins that suppress the Agr-QS function are proposed as potential lead compounds in the anti-virulence strategy for MRSA infections.
• Isolation of two new trichorzin PA derivatives, trichorzin PA X and XI, from the terrestrial fungus Trichoderma harzianum IFM 66736
  Yasumasa Hara; Teruhisa Manome; Wataru Suehiro; Shinji Harada; Yoshikazu Yamagishi; Akiko Takaya; Yasumitsu Ogra; Masami Ishibashi
  Tetrahedron Letters, 121, 154488, 154488, Elsevier BV, 2023年05月, ［査読有り］
  英語, 研究論文（学術雑誌）
• A new 1,2-diketone physalin isolated from Physalis minima and TRAIL-resistance overcoming activity of physalins.
  Teruhisa Manome; Yasumasa Hara; Masami Ishibashi
  Journal of natural medicines, 77, 2, 370, 378, 2023年03月, ［査読有り］, ［筆頭著者］, ［国内誌］
  英語, 研究論文（学術雑誌）, A new 1,2-diketone physalin, physalin XII (1), and 13 known compounds were isolated from the methanol extract of Physalis minima whole plant collected in Thailand. Among them, five physalins (2-6) had tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-resistance overcoming activity, and physalin F (3) was the most active with an IC50 value of 0.39 µM against human gastric adenocarcinoma cell line AGS in the presence of TRAIL (100 ng/mL). An investigation of the TRAIL-resistance overcoming activity of physalins using western blot analysis showed that 3 promoted TRAIL-induced apoptosis by suppressing anti-apoptotic proteins c-FLIP and Bcl-2.
• Isolation of Various Flavonoids with TRAIL Resistance-Overcoming Activity from Blumea lacera.
  Teruhisa Manome; Yasumasa Hara; Masami Ishibashi
  Molecules (Basel, Switzerland), 28, 1, 2022年12月28日, ［査読有り］, ［筆頭著者］, ［国際誌］
  英語, 研究論文（学術雑誌）, Eighteen compounds, including fourteen flavonoids (1-14), one steroid (15), two fatty acids (16,17), and one nitrogen-containing compound (18), were isolated from the methanol extract of the whole Blumea lacera plant collected in Thailand. Compounds 1-11 and 15-17 exhibited tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) resistance-overcoming activity. Among them, bonanzin (2) and cirsilineol (7) had particularly strong TRAIL resistance-overcoming activity, where the IC50 values against the human gastric adenocarcinoma cell line AGS in the presence of TRAIL (100 ng/mL) were 10.7 μM and 5.9 μM, respectively.
• Corrrection to "Two Bioactive Compounds, Uniformides A and B, Isolated from a Culture of Nocardia uniformis IFM0856T in the Presence of Animal Cells".
  Yasumasa Hara; Keiichiro Watanabe; Akiko Takaya; Itsuki Ebihara; Teruhisa Manome; Midori A Arai; Takashi Yaguchi; Masami Ishibashi
  Organic letters, 24, 31, 5867, 5867, 2022年08月12日, ［国際誌］
  英語
• Two Bioactive Compounds, Uniformides A and B, Isolated from a Culture of Nocardia uniformis IFM0856T in the Presence of Animal Cells.
  Yasumasa Hara; Keiichiro Watanabe; Akiko Takaya; Teruhisa Manome; Takashi Yaguchi; Masami Ishibashi
  Organic letters, 24, 27, 4998, 5002, 2022年07月15日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Two new peptides named uniformides A and B (1 and 2, respectively) were isolated from the cultured extracts of Nocardia uniformis IFM0856T in the presence of mouse macrophage-like cell line J774.1, in modified Czapek-Dox medium. These compounds were not produced in a culture containing only N. uniformis but in one that also included J774.1. Compounds 1 and 2 showed high cytotoxicity against J774.1 and suppressed the production of nitric oxide, IL-6, and IL-1β by inhibiting the NF-κB pathway.
• Thannilignan glucoside and 2-(β-glucopyranosyl)-3-isoxazolin-5-one derivative, two new compounds isolated from Terminalia bellirica.
  Teruhisa Manome; Yasumasa Hara; Firoj Ahmed; Samir K Sadhu; Masami Ishibashi
  Journal of natural medicines, 76, 2, 482, 489, 2022年03月, ［査読有り］, ［筆頭著者］, ［国内誌］
  英語, 研究論文（学術雑誌）, Two new compounds, thannilignan 9-O-β-glucoside (1) and 2-(β-glucopyranosyl)-3-isoxazolin-5-one derivative (2), and seven known compounds were isolated from the methanol extract of Terminalia bellirica leaves, collected in Bangladesh. The structures of the compounds were elucidated using spectroscopic analysis. Among these isolated compounds, corilagin (3) was cytotoxic against human gastric adenocarcinoma cell line AGS at an IC50 of 20.8 μM, and β-D-glucopyranose 1,3,6-trigallate (4) exhibited the ability to overcome tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) resistance.
• Isolation of Peptidolipin NA Derivatives from the Culture of Nocardia arthritidis IFM10035T in the Presence of Mouse Macrophage Cells
  Yasumasa Hara; Masami Ishibashi; Daiki Tanimura; Teruhisa Manome; Midori A. Arai; Takashi Yaguchi
  HETEROCYCLES, 104, 1, 185, 185, CLOCKSS Archive, 2022年, ［査読有り］
  英語, 研究論文（学術雑誌）

• Bacterial membrane vesicles: versatile elicitors to activate silent metabolites
  Manome T.; Saeki R.; Yoshimura A.; Wakimoto T.
  The 2026 Gordon Research Conference on Marine Natural Products, 英語, ポスター発表
  2026年03月01日 - 2026年03月06日
• 細菌由来細胞外膜小胞が有する天然物生産 誘導能の一般性
  馬目 照久; 佐伯梨緒; 伊藤匠; 吉村 彩; 脇本 敏幸
  日本生薬学会第71回年会, 2025年09月15日
  2025年09月14日 - 2025年09月15日
• 細胞外膜小胞と二次代謝産物を介した細菌 間相互作用解析
  馬目 照久; 伊藤匠; 佐伯梨緒; 吉村 彩; 脇本 敏幸
  日本微生物生態学会第38回大会, 2025年09月07日
  2025年09月07日 - 2025年09月10日
• A Vesicle-Based Strategy to Stimulate Silent Metabolite Production in Bacteria
  Manome T.; Saeki R.; Takumi I.; Yoshimura A.; Wakimoto T.
  The 32nd IUPAC International Symposium on the Chemistry of Natural Products, 英語, ポスター発表
  2025年08月28日 - 2025年08月31日
• 細菌ゲノム情報から予測する生物活性代謝産物の生産能
  馬目 照久; 中田 隆介; 吉村 彩; 脇本 敏幸
  第51回生体分子科学討論会, 2025年06月26日
• 細菌由来細胞外膜小胞が有する天然物生産誘導能の一般性
  馬目照久; 佐伯梨緒; 吉村彩; 脇本敏幸
  第17回化学生態学研究会, 2025年06月13日, 日本語
• 生物活性発現機構に着目したゲノムマイニングによる天然物探索
  馬目照久; 中田隆介; 吉村彩; 脇本敏幸
  日本薬学会第145年会, 2025年03月27日, 日本語, 口頭発表（一般）
  2025年03月27日 - 2025年03月29日
• 細胞外膜小胞が有する天然物生産誘導能の一般性の検証
  馬目 照久; 佐伯 梨緒; 中田 隆介; 吉村 彩; 脇本 敏幸
  第10回食品薬学シンポジウム10, 2024年10月12日, 日本語, 口頭発表（一般）
• 多様な細菌種由来の細胞外膜小胞を用いた新規天然物探索
  馬目 照久; 佐伯 梨緒; 吉村 彩; 脇本 敏幸
  日本生薬学会第70年会, 2024年09月16日, 日本語, 口頭発表（一般）
• 多様な細菌種由来の細胞外膜小胞を用いた新規天然物探索
  馬目 照久; 佐伯 梨緒; 吉村 彩; 脇本 敏幸
  日本生薬学会北海道支部例会, 2024年07月06日, 日本語, 口頭発表（一般）
• 多様な細菌種由来の細胞外膜小胞を用いた新規天然物探索
  馬目 照久; 佐伯 梨緒; 吉村 彩; 脇本 敏幸
  第16回化学生態学研究会, 2024年06月21日, 日本語, ポスター発表
• 多様な細菌種由来の細胞外膜小胞を用いた新規天然物探索
  馬目 照久; 佐伯 梨緒; 吉村 彩; 脇本 敏幸
  日本薬学会第144年会, 2024年03月29日, 日本語, 口頭発表（一般）
• 放線菌Nocardia carnea IFM 12324からの新規天然物の探索と生合成遺伝子解析
  馬目 照久; 中村 文香; 原 康雅; 高屋 明子; 伴 さやか; 高橋 弘喜; 矢口 貴志; 石橋 正己
  日本薬学会第143年会, 2023年03月28日, 日本語, ポスター発表
• 真菌Trichoderma harzianum IFM66736等からのがん細胞死を誘導する天然物の探索
  馬目 照久; 末広 航; 原 康雅; 原田 真至; 石橋 正己
  第9回食品薬学シンポジウム, 2022年10月15日, 日本語, 口頭発表（一般）
• Physalis minimaからの新規 physalin 探索とその TRAIL 耐性克服作用の作用機序解析
  馬目 照久; 原 康雅; 石橋 正己
  日本生薬学会第68回年会, 2022年09月11日, 日本語, 口頭発表（一般）
• TRAIL耐性克服作用を有するBlumea laceraからの天然物の探索
  馬目 照久; 原 康雅; 石橋 正己
  日本薬学会第142年会, 2022年03月27日, 日本語, ポスター発表
• Search for natural products from Terminalia bellirica and Blumea lacera
  Teruhisa Manome; Yasumasa Hara; Firoj Ahmed; Samir K. Sadhu; Masami Ishibashi
  2021年12月14日, 英語, 口頭発表（一般）
• Search for natural products from Terminalia bellirica with AGS cytotoxicity
  Teruhisa Manome; Yasumasa Hara; Firoj Ahmed; Samir K. Sadhu; Masami Ishibashi
  The 11th JSP-CSP-KSP Joint Symposium on Pharmacognosy, 2021年09月19日, 英語, ポスター発表

• 細菌が放出する細胞外小胞を用いた合理的な天然物探索基盤の構築
  科学研究費助成事業
  2024年04月23日 - 2026年03月31日
  馬目 照久
  日本学術振興会, 特別研究員奨励費, 北海道大学, 24KJ0252