KEIO RESEARCHERS INFORMATION SYSTEM

Career 【 Display / hide 】

Career 【 Display / hide 】

• 2017.04

  -

  2019.03

  The University of Tokyo, Department of Biotechnology, Graduate School of Agricultural and Life Sciences, Research Associate

• 2019.04

  -

  2020.03

  Toyama Prefectural University, Biotechnology Research Center and Department of Biotechnology, Research Associate

• 2020.04

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  2023.03

  Keio University, Faculty of Science and Technology Department of Biosciences and Infomatics, Assistant Professor

Academic Background 【 Display / hide 】

Academic Background 【 Display / hide 】

• 2008.04

  -

  2012.03

  Keio University, 理工学部, 生命情報学科

  University, Graduated

• 2012.04

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  2014.03

  Keio University, 理工学研究科 基礎理工学専攻, 生命システム情報専修

  Graduate School, Completed, Master's course

• 2014.04

  -

  2017.03

  Keio University, 理工学研究科 基礎理工学専攻, 生命システム情報専修

  Graduate School, Completed, Doctoral course

Academic Degrees 【 Display / hide 】

Academic Degrees 【 Display / hide 】

• Doctor (Science), Keio University, Coursework, 2017.03

  Chemistry and biology of novel androgen receptor antagonist antarlides from microbial origin

Research Areas 【 Display / hide 】

Research Areas 【 Display / hide 】

• Nanotechnology/Materials / Chemical biology

• Life Science / Applied microbiology

• Life Science / Pharmaceutical chemistry and drug development sciences

Research Keywords 【 Display / hide 】

Research Keywords 【 Display / hide 】

• Chemical Biology

• Drug Discovery

• Natural Product Chemistry

• Microbiology

• Biosynthesis

Papers 【 Display / hide 】

Papers 【 Display / hide 】

• Dihydromaniwamycin E, a Heat-Shock Metabolite from Thermotolerant Streptomyces sp. JA74, Exhibiting Antiviral Activity against Influenza and SARS-CoV-2 Viruses

  Saito S., Funayama K., Kato W., Okuda M., Kawamoto M., Matsubara T., Sato T., Sato A., Otsuguro S., Sasaki M., Orba Y., Sawa H., Maenaka K., Shindo K., Imoto M., Arai M.A.

  Journal of Natural Products （Journal of Natural Products)  85 （ 11 ） 2583 - 2591 2022.11

  ISSN  01633864

  　View Summary

  Dihydromaniwamycin E (1), a new maniwamycin derivative featuring an azoxy moiety, has been isolated from the culture extract of thermotolerant Streptomyces sp. JA74 along with the known analogue maniwamycin E (2). Compound 1 is produced only by cultivation of strain JA74 at 45 °C, and this type of compound has been previously designated a "heat shock metabolite (HSM)" by our research group. Compound 2 is detected as a production-enhanced metabolite at high temperature. Structures of 1 and 2 are elucidated by NMR and MS spectroscopic analyses. The absolute structure of 1 is determined after the total synthesis of four stereoisomers. Though the absolute structure of 2 has been proposed to be the same as the structure of maniwamycin D, the NMR and the optical rotation value of 2 are in agreement with those of maniwamycin E. Therefore, this study proposes a structural revision of maniwamycins D and E. Compounds 1 and 2 show inhibitory activity against the influenza (H1N1) virus infection of MDCK cells, demonstrating IC50values of 25.7 and 63.2 μM, respectively. Notably, 1 and 2 display antiviral activity against SARS-CoV-2, the causative agent of COVID-19, when used to infect 293TA and VeroE6T cells, with 1 and 2 showing IC50values (for infection of 293TA cells) of 19.7 and 9.7 μM, respectively. The two compounds do not exhibit cytotoxicity in these cell lines at those IC50concentrations.

  • Access to Document (DOI)

• Noaoxazole, a new heat shock metabolite produced by thermotolerant Streptomyces sp. HR41

  Saito S., Suzuki S., Arai M.A.

  Journal of Antibiotics （Journal of Antibiotics)  75 （ 9 ） 509 - 513 2022.09

  ISSN  00218820

  　View Summary

  The thermotolerant strain Streptomyces sp. HR41 was found to produce compound 1 only in a 45 °C culture, and not at the standard temperature. We previously designated this type of compound as a “heat shock metabolite” (HSM). NMR and MS analytical techniques were used to determine that the chemical structure of 1 comprised a methylated-oxazole ring and a linear chain moiety modified with a terminal amide group. Thus, 1 was shown to be a new curromycin analog, which we have designated noaoxazole (1). Compound 1 weakly activated Notch signal reporter activity without exhibiting cytotoxicity against assay cells at the same concentration.

  • Access to Document (DOI)

• Identification of 1β,2α-epoxytagitinin C as a Notch inhibitor, oxidative stress mechanism and its anti-leukemia activity

  Makita Y., Saito S., Tsuchiya A., Ishibashi M., Arai M.A.

  Journal of Natural Medicines （Springer Science and Business Media LLC)  76 （ 1 ） 234 - 243 2022.01

  Research paper (scientific journal), Joint Work, Accepted,  ISSN  13403443

  　View Summary

  Notch signaling plays crucial roles in cell differentiation and proliferation, but aberrant activation of this signaling results in tumorigenesis and cancer progression. Notch signaling is thus a promising drug target for oncotherapy, and the development of Notch signaling inhibitors is eagerly awaited. Notch inhibitory activity-guided fractionation of a Spilanthes acmella extract led to the identification of five sesquiterpene lactones: tagitinin A (1), 1β,2α-epoxytagitinin C (2), tagitinin C (3), orizabin (4), and 2α-hydroxytirotundin (5). 1β,2α-Epoxytagitinin C (2) exhibited Notch signaling inhibition, with an IC50 of 25.6 μM, and was further evaluated for its activity against HPB-ALL, a Notch-activated leukemia cell line. Compound 2 showed potent cytotoxicity against HPB-ALL (IC50 1.7 μM) and arrested the cell cycle at the G2/M phase, but did not induce apoptotic cell death. Notch inhibitory mechanism analysis suggested that compound 2 transcriptionally suppresses Notch1 mRNA. In addition, we found that oxidative stress induction is critical for Notch signaling inhibition and the cytotoxicity of compound 2. This is the first mechanism of small molecule Notch inhibition. Our results demonstrate that 1β,2α-epoxytagitinin C (2) is a potential anti-leukemia agent and further investigation of this compound is warranted. Graphical abstract: [Figure not available: see fulltext.].

  • Access to Document (DOI)

• Mycetoindole, an N-acyl dehydrotryptophan with plant growth inhibitory activity from an actinomycete of the genus Actinomycetospora

  Saito S., Oku N., Igarashi Y.

  Journal of Antibiotics （Springer Science and Business Media LLC)  75 （ 1 ） 44 - 47 2022.01

  Research paper (scientific journal), Joint Work, Lead author, Accepted,  ISSN  00218820

  　View Summary

  A rare actinomycetal strain of the genus Actinomycetospora was found to produce a new tryptophan derivative, designated mycetoindole (1). The structure of 1 was determined to be N-3-methylcrotonoyl (Z)-dehydrotryptophan by NMR and MS analytical methods. Compound 1 reduced the root growth of lettuce Lactuca sativa seedlings at concentrations above 0.1 μM and almost completely inhibited seed germination at 10 μM.

  • Access to Document (DOI)

• Phytohabitols A-C, δ-Lactone-Terminated Polyketides from an Actinomycete of the Genus Phytohabitans

  Saito S., Xiaohanyao Y., Zhou T., Nakajima-Shimada J., Tashiro E., Triningsih D.W., Harunari E., Oku N., Igarashi Y.

  Journal of Natural Products （American Chemical Society (ACS))  85 （ 7 ） 1697 - 1703 2022

  Research paper (scientific journal), Joint Work, Lead author, Accepted,  ISSN  0163-3864

  　View Summary

  Phytohabitols A−C (1−3), new terminally δ-
  lactonized linear polyketides, were isolated from the culture extract
  of a rare actinomycete of the genus Phytohabitans. The structures
  of 1−3, substituted with multiple methyl and hydroxy groups on a
  conjugated and a skipped diene-containing backbone, were
  elucidated by NMR and MS spectroscopic analyses. The absolute
  configuration of 1 was determined by chemical derivatization and
  chiral anisotropic analysis, coupled with ROESY and J-based
  configuration analysis. In addition, closely similar 1H and 13C
  NMR data and optical rotations among 1−3 supported the same stereochemistry of these polyketides. The related streptomycetes metabolites lagunapyrones B, C, and D have α-pyrone rings on the linear part in place of the δ-lactone, but their chirality at the C19−C21 stereocenters were opposite from those described here, posing a question on the previous assignment made solely by comparison of the optical rotations of four possible diastereomers. Compounds 1−3 inhibited migration of cancer cells with IC50 values of 15, 11, and 8.3 μM, respectively, at noncytotoxic concentrations. In addition, 1−3 displayed potent antitrypanosomal activity against Trypanosoma cruzi with IC50 values of 12, 6.4, and 18 μM, comparable to a commonly used therapeutic drug, benznidazole (IC50 16 μM).

  • Access to Document (DOI)

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Reviews, Commentaries, etc. 【 Display / hide 】

Reviews, Commentaries, etc. 【 Display / hide 】

• 天然物ケミカルバイオロジー研究の現状 –前立腺がん治療薬を例として–

  齋藤　駿, 井本　正哉

  月刊「ケミカルエンジニヤリング」 (化学工業社)  62   52 - 58 2017.10

  Joint Work, Lead author

• 新奇天然化合物ハンティング

  齋藤　駿, 井本　正哉

  月刊化学 (株式会社 化学同人)  71   68 - 69 2016.07

  Joint Work, Lead author

• 創薬を志向した天然化合物の探索研究

  齋藤　駿, 田代　悦, 井本　正哉

  化学と生物 (公益社団法人 日本農芸化学会)  52   466 - 472 2014.07

  Joint Work, Lead author

Research Projects of Competitive Funds, etc. 【 Display / hide 】

Research Projects of Competitive Funds, etc. 【 Display / hide 】

• 放線菌が生産する熱ショック代謝物（HSM）の生産制御および耐熱性促進機構の解析

  2023.04

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  2026.03

  MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Early-Career Scientists , Principal investigator

• 放線菌が生産する熱ショック代謝物 (HSM) の耐熱性促進機構の解析

  2023.04

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  2024.03

  公益財団法人 野田産業科学研究所, 奨励研究助成, Principal investigator

• 未研究希少放線菌の二次代謝能の解明を通じた新規植物生長制御物質の探索

  2020.04

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  2023.03

  MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Early-Career Scientists , Principal investigator

Awards 【 Display / hide 】

Awards 【 Display / hide 】

• 2021 JA Ōmura Awards

  2022.12, The Journal of Antibiotics

  Type of Award： Honored in official journal of a scientific society, scientific journal

• 第32回新薬創製談話会 研究奨励賞

  2022.09

  Type of Award： Award from Japanese society, conference, symposium, etc.

• 藤原賞

  2017.03, 慶應義塾大学 理工学部

  Type of Award： Keio commendation etc.

• 第8回日韓ケミカルバイオロジーシンポジウム Best poster award

  2016.01

  Type of Award： Award from international society, conference, symposium, etc.

Courses Taught 【 Display / hide 】

Courses Taught 【 Display / hide 】

• TOPICS IN BIOSCIENCES AND INFORMATICS 2

  2024

• SEMINAR IN BIOSCIENCES AND INFORMATICS

  2024

• LABORATORIES IN SCIENCE AND TECHNOLOGY

  2024

• INTRODUCTION TO BIOLOGY TODAY

  2024

• GLOBAL LEADERSHIP SEMINAR

  2024

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Courses Previously Taught 【 Display / hide 】

Courses Previously Taught 【 Display / hide 】

• 生命情報特別講義第2

  慶應義塾大学

  2020.04

  -

  Present

  , 

  Spring Semester, Lecture