新たな創薬資源の採集調査と新奇天然物生合成マシナリーの探索と解明

• Project/Area Number: 20KK0173
• Research Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 47:Pharmaceutical sciences and related fields
• Research Institution: The University of Tokyo
• Principal Investigator: 阿部 郁朗 東京大学, 大学院薬学系研究科(薬学部), 教授 (40305496)
• Co-Investigator(Kenkyū-buntansha): 淡川 孝義 国立研究開発法人理化学研究所, 環境資源科学研究センター, チームリーダー (80609834) ; 森 貴裕 東京大学, 大学院薬学系研究科(薬学部), 准教授 (60734564) ; 牛丸 理一郎 東京大学, 大学院薬学系研究科(薬学部), 助教 (10873648)
• Project Period (FY): 2020-10-27 – 2024-03-31
• Project Status: Completed (Fiscal Year 2023)
• Budget Amount: ¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000); Fiscal Year 2023: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2022: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2021: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2020: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
• Keywords: 創薬資源採集調査 / 天然物生合成 / 生合成マシナリー / 生物多様性 / 中国南西部

Outline of Research at the Start

中国・曁南大学との共同研究により、新たな創薬資源の採集調査を実施する。新奇天然物生合成マシナリーを探索し、その詳細を解明する。具体的には、生物多様性ホットスポットとされる中国南西部における未開拓薬用資源微生物を対象として、新奇生合成酵素遺伝子を探索する。さらに、その生合成反応機構の詳細を解明し、複雑骨格薬用天然物の生合成マシナリーの合理的再構築により、狙ったものを正確に作る、天然物を凌ぐ新規希少有用物質の大量安定供給をめざす。研究代表者を含め、若手研究者を戦略的に当該地域に派遣し、国際共同研究を強力に推進することで、独創的、先駆的な研究を格段に発展させる。

Outline of Annual Research Achievements

以下の４つの項目を2020年度から4年間の計画で遂行した。
（１）植物内生菌、土壌微生物の最終単離（中国側が主導）長鎖対象地域として、未開拓薬用資源の宝庫、生物多様性ホットスポットとされる、中国南西部を選択した。（２）低分子化合物の単離構造決定、生物活性評価（中国側が主導）上述したカルチャー・コレクションについて、異なる培養条件下で二次代謝産物生産を詳細に検討し、微生物が生産する二次代謝産物とその生物活性を網羅的に解析した。（３）生合成マシナリーの解明と物質生産系の構築（日本側と中国側で同時進行）上述したカルチャー・コレクションで、有用な生物活性物質生産能を示した微生物について、バイオインフォマティクスの技術を駆使したゲノムマイニングにより、テルペン、ポリケタイド、ペプチドなど、生物間相互作用に重要な役割を演ずる可能性が予想される創薬シード合物の新奇生合成酵素遺伝子を網羅的に探索し、その生合成マシナリーの詳細を解明る。大腸菌や酵母、麹菌などを宿主として、これら遺伝子の異種発現による物質生産系を構築する。有機化学を基盤として、生合成反応機構の詳細を酵素遺伝子レベルで明らかにする。（４）酵素結晶構造解析、機能改変と生合成リデザイン（日本側が主導）X線結晶構造解析により、酵素反応の立体構造基盤を明らかにするとともに、結晶構造に基づく酵素触媒機能の拡張と最適化をめざす。さらなる構造多様性の拡大と物質生産系の構築を実現し、所望の構造を有する、天然物を凌ぐ新規有用活性物質の安定供給をめざした。

最終年度も、質量ともに充実した研究成果をあげることに成功した。また、Enfumafungin抗生物質の生合成マシナリーの解明（JACS2024）、生薬クコの実（枸杞子）有効成分の生合成に関わる新奇配糖化酵素の構造機能解析（Nat Commun, in revision）など、共同研究成果が着実に多くの優れた共著論文に実りつつある。

Research Products

• [Int'l Joint Research] ジ南大学/中国科学院/浙江大学(中国)
• [Int'l Joint Research] チェコ科学アカデミー(チェコ)
• [Int'l Joint Research] ノースカロライナ大/テキサス大/カーネギーメロン大(米国)
• [Int'l Joint Research] マンチェスター大(英国)
• [Int'l Joint Research] オークランド大(ニュージーランド)
• [Int'l Joint Research]
• [Int'l Joint Research] 曁南大学/武漢大学/北京中医薬大学(中国)
• [Int'l Joint Research] ボン大学(ドイツ)
• [Int'l Joint Research] ジ南大学/中国科学院/浙江大学(中国)
• [Int'l Joint Research] 曁南大学/武漢大学/中国科学院(中国)
• [Journal Article] Unusual cysteine modifications in natural product biosynthesis (2024)
  • Author(s): Gao Yaojie、Zhu Yuhao、Awakawa Takayoshi、Abe Ikuro
  • Journal Title: RSC Chemical Biology Volume: 5 Issue: 4 Pages: 299-311
  • DOI: 10.1039/d4cb00020j
  • Peer Reviewed / Open Access
• [Journal Article] Characterization of Aziridine-Forming α-Ketoglutarate-Dependent Oxygenase in L-Isovaline Biosynthesis (2024)
  • Author(s): Zhou Lu、Awakawa Takayoshi、Ushimaru Richiro、Kanaida Masahiro、Abe Ikuro
  • Journal Title: Organic Letters Volume: 26 Issue: 3 Pages: 724-727
  • DOI: 10.1021/acs.orglett.3c04185
  • Peer Reviewed
• [Journal Article] Lincosamide Antibiotics: Structure, Activity, and Biosynthesis (2024)
  • Author(s): Mori Takahiro、Abe Ikuro
  • Journal Title: ChemBioChem Volume: 25 Issue: 6
  • DOI: 10.1002/cbic.202300840
  • Peer Reviewed
• [Journal Article] Biosynthesis of enfumafungin-type antibiotic reveals an unusual enzymatic fusion pattern and unprecedented C-C bond cleavage (2024)
  • Author(s): Cao, Z.-Q., Wang, G.-Q., Luo, R., Gao, Y.-H., Lv, J.-M., Qin, S.-Y., Chen, G.-D., Awakawa, T., Bao, X.-F., Mei, Q.-H., Yao, X.-S., Hu, D., Abe, I., Gao, H.
  • Journal Title: J. Am. Chem. Soc. Volume: 146
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Discovery of (±)-penindolenes reveals an unusual indole ring cleavage pathway catalyzed by P450 monooxygenase (2024)
  • Author(s): Meng, L.-H.,# Awakawa, T.,# Li, X.-M., Quan, Z., Yang, S.-Q., Wang, B.-G., Abe, I.
  • Journal Title: Angew. Chem. Int. Ed. Volume: 63
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Functional and structural dissection of glycosyltransferases underlying the glycodiversity of wolfberry-derived bioactive ingredients lycibarbarspermidines (2024)
  • Author(s): Shao-Yang Li, Gao-Qian Wang, Liang Long, Jia-Ling Gao, Zheng-Qun Zhou, Yong-Heng Wang, Jian-Ming Lv, Guo-Dong Chen, Dan Hu, Ikuro Abe & Hao Gao
  • Journal Title: Nature Communications Volume: 15
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Molecular basis for carrier protein-dependent amide bond formation in the biosynthesis of lincosamide antibiotics (2023)
  • Author(s): Mori Takahiro、Kadlcik Stanislav、Lyu Shuang、Kamenik Zdenek、Sakurada Kosuke、Mazumdar Aninda、Wang Huibin、Janata Jiri、Abe Ikuro
  • Journal Title: Nature Catalysis Volume: 6 Issue: 6 Pages: 531-542
  • DOI: 10.1038/s41929-023-00971-y
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Back-to-back cycloadditions in nature (2023)
  • Author(s): Ushimaru Richiro、Abe Ikuro
  • Journal Title: Nature Chemistry Volume: 15 Issue: 8 Pages: 1056-1057
  • DOI: 10.1038/s41557-023-01282-2
  • Peer Reviewed
• [Journal Article] Mechanistic Analysis of Stereodivergent Nitroalkane Cyclopropanation Catalyzed by Nonheme Iron Enzymes (2023)
  • Author(s): Ushimaru Richiro、Cha Lide、Shimo Shotaro、Li Xiaojun、Paris Jared C.、Mori Takahiro、Miyamoto Kazunori、Coffer Lindsay、Uchiyama Masanobu、Guo Yisong、Chang Wei-chen、Abe Ikuro
  • Journal Title: Journal of the American Chemical Society Volume: 145 Issue: 44 Pages: 24210-24217
  • DOI: 10.1021/jacs.3c08413
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Structural and Mechanistic Insights into the C?C Bond-Forming Rearrangement Reaction Catalyzed by Heterodimeric Hinokiresinol Synthase (2023)
  • Author(s): Ushimaru Richiro、Ding Yiling、Mori Takahiro、Miyamoto Kazunori、Uchiyama Masanobu、Abe Ikuro
  • Journal Title: Journal of the American Chemical Society Volume: 145 Issue: 40 Pages: 21966-21973
  • DOI: 10.1021/jacs.3c06762
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Multiple C-C Bond Cleavage Reactions Catalyzed by Tolyporphin Tetrapyrrole Biosynthetic Enzymes (2023)
  • Author(s): Richiro Ushimaru, Jiaqi Lyu, Meiqi Ling, Ikuro Abe
  • Journal Title: Journal of the American Chemical Society Volume: 145 Issue: 17 Pages: 9834-9839
  • DOI: 10.1021/jacs.3c01993
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Assembling neuroactive alkaloids (2023)
  • Author(s): Ushimaru Richiro、Abe Ikuro
  • Journal Title: Nature Plants Volume: 9 Issue: 12 Pages: 1946-1947
  • DOI: 10.1038/s41477-023-01586-8
  • Peer Reviewed
• [Journal Article] Structure‐Function Analysis of the S‐Glycosylation Reaction in the Biosynthesis of Lincosamide Antibiotics (2023)
  • Author(s): Mori Takahiro、Sun Xin、Kadlcik Stanislav、Janata Jiri、Abe Ikuro
  • Journal Title: Angewandte Chemie International Edition Volume: 62 Issue: 29
  • DOI: 10.1002/anie.202304989
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Catalytic Mechanism of Nonglycosidic C-N Bond Formation by the Pseudoglycosyltransferase Enzyme VldE (2023)
  • Author(s): Tsunoda Takeshi、Abuelizz Hatem A.、Samadi Arash、Wong Chin Piow、Awakawa Takayoshi、Brumsted Corey J.、Abe Ikuro、Mahmud Taifo
  • Journal Title: ACS Catalysis Volume: 13 Issue: 20 Pages: 13369-13382
  • DOI: 10.1021/acscatal.3c02404
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] C?N and C?S bond formation by cytochrome P450 enzymes (2023)
  • Author(s): Ushimaru Richiro、Abe Ikuro
  • Journal Title: Trends in Chemistry Volume: 5 Issue: 7 Pages: 526-536
  • DOI: 10.1016/j.trechm.2023.04.008
  • Peer Reviewed
• [Journal Article] Genomic and Spectroscopic Signature-Based Discovery of Natural Macrolactams (2023)
  • Author(s): Shin Yern-Hyerk、Im Ji Hyeon、Kang Ilnam、Kim Eunji、Jang Sung Chul、Cho Eunji、Shin Daniel、Hwang Sunghoon、Du Young Eun、Huynh Thanh-Hau、Ko Keebeom、Ko Yoon-Joo、Nam Sang-Jip、Awakawa Takayoshi、Lee Jeeyeon、Hong Suckchang、Abe Ikuro、Moore Bradley S.、Fenical William、Yoon Yeo Joon、Cho Jang-Cheon、Oh Dong-Chan
  • Journal Title: Journal of the American Chemical Society Volume: 145 Issue: 3 Pages: 1886-1896
  • DOI: 10.1021/jacs.2c11527
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Structure-based engineering of α-ketoglutarate dependent oxygenases in fungal meroterpenoid biosynthesis (2023)
  • Author(s): Awakawa Takayoshi、Mori Takahiro、Ushimaru Richiro、Abe Ikuro
  • Journal Title: Natural Product Reports Volume: 40 Issue: 1 Pages: 46-61
  • DOI: 10.1039/d2np00014h
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Diverse enzymatic chemistry for propionate side chain cleavages in tetrapyrrole biosynthesis (2023)
  • Author(s): Ushimaru Richiro、Lyu Jiaqi、Abe Ikuro
  • Journal Title: Journal of Industrial Microbiology and Biotechnology Volume: 50 Issue: 1
  • DOI: 10.1093/jimb/kuad016
  • Peer Reviewed / Open Access
• [Journal Article] Unusual Dioxygen-Dependent Reactions Catalyzed by Nonheme Iron Enzymes in Natural Product Biosynthesis (2022)
  • Author(s): Ushimaru Richiro、Abe Ikuro
  • Journal Title: ACS Catalysis Volume: 13 Issue: 2 Pages: 1045-1076
  • DOI: 10.1021/acscatal.2c05247
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Discovery of non-squalene triterpenes (2022)
  • Author(s): Tao Hui、Lauterbach Lukas、Bian Guangkai、Chen Rong、Hou Anwei、Mori Takahiro、Cheng Shu、Hu Ben、Lu Li、Mu Xin、Li Min、Adachi Naruhiko、Kawasaki Masato、Moriya Toshio、Senda Toshiya、Wang Xinghuan、Deng Zixin、Abe Ikuro、Dickschat Jeroen S.、Liu Tiangang
  • Journal Title: Nature Volume: 606 Issue: 7913 Pages: 414-419
  • DOI: 10.1038/s41586-022-04773-3
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Stereoselectivity and Substrate Specificity of the Fe(II)/α-Ketoglutarate-Dependent Oxygenase TqaL (2022)
  • Author(s): Tao Hui、Ushimaru Richiro、Awakawa Takayoshi、Mori Takahiro、Uchiyama Masanobu、Abe Ikuro
  • Journal Title: Journal of the American Chemical Society Volume: 144 Issue: 47 Pages: 21512-21520
  • DOI: 10.1021/jacs.2c08116
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Molecular insights into the unusually promiscuous and catalytically versatile Fe(II)/α-ketoglutarate-dependent oxygenase SptF. (2022)
  • Author(s): Tao, H., # Mori, T., # Chen, H., Lyu, S., Nonoyama, A., Lee, S., Abe, I. (#equall contribution)
  • Journal Title: Nature Commun Volume: 13 Issue: 1 Pages: 95-95
  • DOI: 10.1038/s41467-021-27636-3
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Noncanonical Functions of Enzyme Cofactors as Building Blocks in Natural Product Biosynthesis (2022)
  • Author(s): Barra Lena、Awakawa Takayoshi、Abe Ikuro
  • Journal Title: JACS Au Volume: 2 Issue: 9 Pages: 1950-1963
  • DOI: 10.1021/jacsau.2c00391
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Identification of a diarylpentanoid-producing polyketide synthase revealing an unusual biosynthetic pathway of 2-(2-phenylethyl)chromones in agarwood (2022)
  • Author(s): Wang Xiao-Hui、Gao Bo-Wen、Nakashima Yu、Mori Takahiro、Zhang Zhong-Xiu、Kodama Takeshi、Lee Yuan-E、Zhang Ze-Kun、Wong Chin-Piow、Liu Qian-Qian、Qi Bo-Wen、Wang Juan、Li Jun、Liu Xiao、Abe Ikuro、Morita Hiroyuki、Tu Peng-Fei、Shi She-Po
  • Journal Title: Nature Communications Volume: 13 Issue: 1 Pages: 348-348
  • DOI: 10.1038/s41467-022-27971-z
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Characterization of Enzymes Catalyzing the Initial Steps of the β-Lactam Tabtoxin Biosynthesis (2022)
  • Author(s): Lyu Jiaqi、Ushimaru Richiro、Abe Ikuro
  • Journal Title: Organic Letters Volume: 24 Issue: 18 Pages: 3337-3341
  • DOI: 10.1021/acs.orglett.2c00878
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Structure-based redesign of Fe(<scp>ii</scp>)/2-oxoglutarate-dependent oxygenase AndA to catalyze spiro-ring formation (2022)
  • Author(s): Mori Takahiro、Nakashima Yu、Chen Heping、Hoshino Shotaro、Mitsuhashi Takaaki、Abe Ikuro
  • Journal Title: Chemical Communications Volume: 58 Issue: 36 Pages: 5510-5513
  • DOI: 10.1039/d2cc00736c
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Rational Engineering of the Nonheme Iron- and 2-Oxoglutarate-Dependent Oxygenase SptF (2022)
  • Author(s): Mori Takahiro、Yu Ziheng、Tao Hui、Abe Ikuro
  • Journal Title: Organic Letters Volume: 24 Issue: 8 Pages: 1737-1741
  • DOI: 10.1021/acs.orglett.2c00409
  • Peer Reviewed
• [Journal Article] Cordycicadins A?D, Antifeedant Polyketides from the Entomopathogenic Fungus <i>Cordyceps cicadae</i> JXCH1 (2022)
  • Author(s): Li Xinyang、Chen He-Ping、Zhou Lin、Fan Jing、Awakawa Takayoshi、Mori Takahiro、Ushimaru Richiro、Abe Ikuro、Liu Ji-Kai
  • Journal Title: Organic Letters Volume: 24 Issue: 47 Pages: 8627-8632
  • DOI: 10.1021/acs.orglett.2c03432
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] A Multifunctional Cytochrome P450 and a Meroterpenoid Cyclase in the Biosynthesis of Fungal Meroterpenoid Atlantinone B (2022)
  • Author(s): Qi Bo-wen、Li Na、Zhang Bei-bei、Zhang Ze-kun、Wang Wen-jing、Liu Xiao、Wang Juan、Awakawa Takayoshi、Tu Peng-fei、Abe Ikuro、Shi She-po、Li Jun
  • Journal Title: Organic Letters Volume: 24 Issue: 13 Pages: 2526-2530
  • DOI: 10.1021/acs.orglett.2c00684
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Biosynthesis of dihydroxyardeemin by heterologous expression (2022)
  • Author(s): Zhou Lu、Abe Ikuro、Awakawa Takayoshi
  • Journal Title: Tetrahedron Volume: 127 Pages: 133095-133095
  • DOI: 10.1016/j.tet.2022.133095
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Harnessing Fe(II)/α-ketoglutarate-dependent oxygenases for structural diversification of fungal meroterpenoids (2022)
  • Author(s): Tao Hui、Abe Ikuro
  • Journal Title: Current Opinion in Biotechnology Volume: 77 Pages: 102763-102763
  • DOI: 10.1016/j.copbio.2022.102763
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Structural basis for endoperoxide-forming oxygenases (2022)
  • Author(s): Mori Takahiro、Abe Ikuro
  • Journal Title: Beilstein Journal of Organic Chemistry Volume: 18 Pages: 707-721
  • DOI: 10.3762/bjoc.18.71
  • Peer Reviewed / Open Access
• [Journal Article] β-NAD as a building block in natural product biosynthesis (2021)
  • Author(s): Barra Lena、Awakawa Takayoshi、Shirai Kohei、Hu Zhijuan、Bashiri Ghader、Abe Ikuro
  • Journal Title: Nature Volume: 600 Issue: 7890 Pages: 754-758
  • DOI: 10.1038/s41586-021-04214-7
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Heterodimeric Non-heme Iron Enzymes in Fungal Meroterpenoid Biosynthesis (2021)
  • Author(s): Li Xinyang、Awakawa Takayoshi、Mori Takahiro、Ling Meiqi、Hu Dan、Wu Bin、Abe Ikuro
  • Journal Title: Journal of the American Chemical Society Volume: 143 Issue: 50 Pages: 21425-21432
  • DOI: 10.1021/jacs.1c11548
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Molecular insights into the endoperoxide formation by Fe(II)/α-KG-dependent oxygenase NvfI (2021)
  • Author(s): Mori Takahiro、Zhai Rui、Ushimaru Richiro、Matsuda Yudai、Abe Ikuro
  • Journal Title: Nature Communications Volume: 12 Issue: 1 Pages: 4417-4417
  • DOI: 10.1038/s41467-021-24685-6
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] C-Glycoside metabolism in the gut and in nature: Identification, characterization, structural analyses and distribution of C-C bond-cleaving enzymes (2021)
  • Author(s): Mori Takahiro、Kumano Takuto、He Haibing、Watanabe Satomi、Senda Miki、Moriya Toshio、Adachi Naruhiko、Hori Sanae、Terashita Yuzu、Kawasaki Masato、Hashimoto Yoshiteru、Awakawa Takayoshi、Senda Toshiya、Abe Ikuro、Kobayashi Michihiko
  • Journal Title: Nature Communications Volume: 12 Issue: 1 Pages: 6294-6294
  • DOI: 10.1038/s41467-021-26585-1
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Stereodivergent Nitrocyclopropane Formation during Biosynthesis of Belactosins and Hormaomycins (2021)
  • Author(s): Shimo Shotaro、Ushimaru Richiro、Engelbrecht Alicia、Harada Mei、Miyamoto Kazunori、Kulik Andreas、Uchiyama Masanobu、Kaysser Leonard、Abe Ikuro
  • Journal Title: Journal of the American Chemical Society Volume: 143 Issue: 44 Pages: 18413-18418
  • DOI: 10.1021/jacs.1c10201
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Aziridine Formation by a Fe ^II /α‐Ketoglutarate Dependent Oxygenase and 2‐Aminoisobutyrate Biosynthesis in Fungi (2021)
  • Author(s): Bunno Reito、Awakawa Takayoshi、Mori Takahiro、Abe Ikuro
  • Journal Title: Angewandte Chemie International Edition Volume: 60 Issue: 29 Pages: 15827-15831
  • DOI: 10.1002/anie.202104644
  • Peer Reviewed
• [Journal Article] One Polyketide Synthase, Two Distinct Products: Trans‐Acting Enzyme‐Controlled Product Divergence in Calbistrin Biosynthesis (2021)
  • Author(s): Tao Hui、Mori Takahiro、Wei Xingxing、Matsuda Yudai、Abe Ikuro
  • Journal Title: Angewandte Chemie International Edition Volume: 60 Issue: 16 Pages: 8851-8858
  • DOI: 10.1002/anie.202016525
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Structural Basis for Isomerization Reactions in Fungal Tetrahydroxanthone Biosynthesis and Diversification (2021)
  • Author(s): Yang Jiali、Mori Takahiro、Wei Xingxing、Matsuda Yudai、Abe Ikuro
  • Journal Title: Angewandte Chemie International Edition Volume: 60 Issue: 35 Pages: 19458-19465
  • DOI: 10.1002/anie.202107884
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Biosynthesis of alkyne-containing natural products (2021)
  • Author(s): Li Xinyang、Lv Jian-Ming、Hu Dan、Abe Ikuro
  • Journal Title: RSC Chemical Biology Volume: 2 Issue: 1 Pages: 166-180
  • DOI: 10.1039/d0cb00190b
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Enzymology and biosynthesis of the orsellinic acid derived medicinal meroterpenoids (2021)
  • Author(s): Tao Hui、Abe Ikuro
  • Journal Title: Current Opinion in Biotechnology Volume: 69 Pages: 52-59
  • DOI: 10.1016/j.copbio.2020.11.016
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Microbial soluble aromatic prenyltransferases for engineered biosynthesis (2021)
  • Author(s): Chen He-Ping、Abe Ikuro
  • Journal Title: Synthetic and Systems Biotechnology Volume: 6 Issue: 2 Pages: 51-62
  • DOI: 10.1016/j.synbio.2021.02.001
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Extensive expanding the chemical diversity of fusidane-type antibiotics using a stochastic combinational strategy (2020)
  • Author(s): Song Xiaojun、Lv Jianming、Cao Zhiqin、Huang Huiyun、Chen Guodong、Awakawa Takayoshi、Hu Dan、Gao Hao、Abe Ikuro、Yao Xinsheng
  • Journal Title: Acta Pharmaceutica Sinica B Volume: 10 Issue: 6 Pages: 1676-1685
  • DOI: 10.1016/j.apsb.2020.12.007
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Biosynthesis of biscognienyne B involving an unprecedented cytochrome P450‐dependent alkynylation (2020)
  • Author(s): Abe Ikuro、Lv Jian-Ming、Gao Yao-Hui、Zhao Huan、Awakawa Takayoshi、Liu Ling、Chen Guo-Dong、Yao Xin-Sheng、Hu Dan、Gao Hao
  • Journal Title: Angewandte Chemie International Edition Volume: 59 Issue: 32 Pages: 13531-13536
  • DOI: 10.1002/anie.202004364
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Discovery of the cryptic function of terpene cyclases as aromatic prenyltransferases (2020)
  • Author(s): He Haibing、Bian Guangkai、Herbst-Gervasoni Corey J.、Mori Takahiro、Shinsky Stephen A.、Hou Anwei、Mu Xin、Huang Minjian、Cheng Shu、Deng Zixin、Christianson David W.、Abe Ikuro、Liu Tiangang
  • Journal Title: Nature Communications Volume: 11 Issue: 1 Pages: 3958-3958
  • DOI: 10.1038/s41467-020-17642-2
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Structural Diversification of Andiconin-Derived Natural Products by α-Ketoglutarate-Dependent Dioxygenases (2020)
  • Author(s): Bai Tongxuan、Matsuda Yudai、Tao Hui、Mori Takahiro、Zhang Yonghui、Abe Ikuro
  • Journal Title: Organic Letters Volume: 22 Issue: 11 Pages: 4311-4315
  • DOI: 10.1021/acs.orglett.0c01358
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Sporormielones A?E, bioactive novel C?C coupled orsellinic acid derivative dimers, and their biosynthetic origin (2020)
  • Author(s): Chen Guo-Dong、Hu Dan、Huang Mei-Juan、Tang Jia、Wang Xiao-Xia、Zou Jian、Xie Jun、Zhang Wei-Guang、Guo Liang-Dong、Yao Xin-Sheng、Abe Ikuro、Gao Hao
  • Journal Title: Chemical Communications Volume: 56 Issue: 33 Pages: 4607-4610
  • DOI: 10.1039/d0cc00855a
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Deciphering the Biosynthetic Mechanism of Pelletierine in Lycopodium Alkaloid Biosynthesis (2020)
  • Author(s): Wang Juan、Zhang Ze-Kun、Jiang Fang-Fang、Qi Bo-Wen、Ding Ning、Hnin Saw Yu Yu、Liu Xiao、Li Jun、Wang Xiao-hui、Tu Peng-Fei、Abe Ikuro、Morita Hiroyuki、Shi She-Po
  • Journal Title: Organic Letters Volume: 22 Issue: 21 Pages: 8725-8729
  • DOI: 10.1021/acs.orglett.0c03339
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Molecular Basis for Sesterterpene Diversity Produced by Plant Terpene Synthases (2020)
  • Author(s): Chen Qingwen、Li Jianxu、Liu Zhixi、Mitsuhashi Takaaki、Zhang Yuting、Liu Haili、Ma Yihua、He Juan、Shinada Tetsuro、Sato Tsutomu、Wang Yong、Liu Hongwei、Abe Ikuro、Zhang Peng、Wang Guodong
  • Journal Title: Plant Communications Volume: 1 Issue: 5 Pages: 100051-100051
  • DOI: 10.1016/j.xplc.2020.100051
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Identification and characterization of N9-methyltransferase involved in converting caffeine into non-stimulatory theacrine in tea (2020)
  • Author(s): Zhang Yue-Hong、Li Yi-Fang、Wang Yongjin、Tan Li、Cao Zhi-Qin、Xie Chao、Xie Guo、Gong Hai-Biao、Sun Wan-Yang、Ouyang Shu-Hua、Duan Wen-Jun、Lu Xiaoyun、Ding Ke、Kurihara Hiroshi、Hu Dan、Zhang Zhi-Min、Abe Ikuro、He Rong-Rong
  • Journal Title: Nature Communications Volume: 11 Issue: 1 Pages: 1473-1473
  • DOI: 10.1038/s41467-020-15324-7
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Unusual Enzyme Reactions in Natural Product Biosynthesis (2023)
  • Author(s): Ikuro Abe
  • Organizer: 4th International Conference on Natural Product Discovery and Development in the Genomic Era, San Diego, USA
  • Int'l Joint Research / Invited
• [Presentation] Unusual Enzyme Reactions in Natural Product Biosynthesis (2023)
  • Author(s): Ikuro Abe
  • Organizer: PSJ-PSK Joint Symposium: Natural Products in Drug Discovery, the 143rd Annual Meeting of the Pharmaceutical Society of Japan, Sapporo, Japan
  • Int'l Joint Research / Invited
• [Presentation] Unusual Enzyme Reactions in Natural Product Biosynthesis (2023)
  • Author(s): Ikuro Abe
  • Organizer: Gordon Research Conference, Enzymes, Coenzymes and Metabolic Pathways, Waterville Valley, NH, USA
  • Int'l Joint Research / Invited
• [Presentation] b-NAD as a Building Block in Natural Product Biosynthesis (2023)
  • Author(s): Ikuro Abe
  • Organizer: Enzyme Engineering XXVII, Singapore, Singapore
  • Int'l Joint Research / Invited
• [Presentation] Unusual Enzyme Reactions in Natural Product Biosynthesis (2023)
  • Author(s): Ikuro Abe
  • Organizer: New Zealand Society for Biochemistry and Molecular Biology (NZSBMB) 50th Anniversary Conference, Canterbury, New Zealand
  • Int'l Joint Research / Invited
• [Presentation] NAD as a Building Block in Natural Product Biosynthesis (2022)
  • Author(s): Ikuro Abe
  • Organizer: Directing Biosynthesis VI, Edinburgh, UK
  • Int'l Joint Research / Invited
• [Presentation] Molecular Basis for the P450-catalyzed C-N Bond Formation in Indolactam Biosynthesis (2022)
  • Author(s): Ikuro Abe
  • Organizer: International Conference on Cytochrome P450, Washington, D.C., USA
  • Int'l Joint Research / Invited
• [Presentation] Unusual Enzyme Reactions in Natural Product Biosynthesis (2022)
  • Author(s): Ikuro Abe
  • Organizer: Gordon Research Conference, Natural Products and Bioactive Compounds, Proctor Academy, NH, USA
  • Int'l Joint Research / Invited
• [Presentation] NAD as a Building Block in Natural Product Biosynthesis (2022)
  • Author(s): Ikuro Abe
  • Organizer: 15th Asian Congress on Biotechnology, Bali, Indonesia
  • Int'l Joint Research / Invited
• [Presentation] NAD as a Building Block in Natural Product Biosynthesis (2022)
  • Author(s): Ikuro Abe
  • Organizer: 29th Federation of Asian and Oceanian Biochemists and Molecular Biologists (FAOBMB) Conference & 2022 Chinese Society of Biochemistry and Molecular Biology Conference, Shenzhen (Online)
  • Int'l Joint Research / Invited
• [Presentation] Unusual Enzyme Reactions in Natural Product Biosynthesis (2022)
  • Author(s): Ikuro Abe
  • Organizer: 4th Lijiang International Forum on Pharmaceutical Sciences, Guiling (Online), China
  • Int'l Joint Research / Invited
• [Presentation] Unusual Enzyme Reactions in Natural Product Biosynthesis (2022)
  • Author(s): Ikuro Abe
  • Organizer: Conference on Synthetic Biology Approaches and its Applications, Osaka (Online), Japan
  • Int'l Joint Research / Invited
• [Remarks] 東京大学大学院薬学系研究科天然物化学教室
  • URL: https://tennen.f.u-tokyo.ac.jp/head.htm
• [Remarks] 東京大学大学院薬学系研究科天然物化学教室
  • URL: http://www.f.u-tokyo.ac.jp/~tennen/head.htm