KEIO RESEARCHERS INFORMATION SYSTEM

Career 【 Display / hide 】

Career 【 Display / hide 】

• 2019.04

  -

  2022.03

  Next generation Natural Product Chemistry, Research & Development Dept., Senior Researcher

• 2022.04

  -

  2022.06

  Keio Uninversity, Faculty of Pharmacy, 特任助教

• 2022.07

  -

  Present

  Keio Uninversity, Faculty of Pharmacy, 助教

Academic Background 【 Display / hide 】

Academic Background 【 Display / hide 】

• 2010.04

  -

  2014.03

  Tohoku University, 薬学部, 創薬科学科

  University, Graduated

• 2014.04

  -

  2016.03

  Tohoku University, 薬学研究科

  Graduate School, Completed, Master's course

• 2016.04

  -

  2019.03

  Tohoku University, 薬学研究科

  Graduate School, Completed, Doctoral course

Academic Degrees 【 Display / hide 】

Academic Degrees 【 Display / hide 】

• 博士(薬科学）, Tohoku University, Coursework, 2019.03

  中員環天然化合物の構造を基盤としたアルカロイド型化合物ライブラリーの構築

Research Areas 【 Display / hide 】

Research Areas 【 Display / hide 】

• Life Science / Pharmaceutical chemistry and drug development sciences (Natural Product Chemistry, Medicinal Chemistry, Organic Chemistry)

Papers 【 Display / hide 】

Papers 【 Display / hide 】

• Compound–compound interaction analysis of baicalin and berberine derivatives in aqueous solution

  Uekusa Y., Tanioka C., Nakamoto K., Tsutsumi R., Iida C., Enshu N., Nishimura T., Kiuchi F., Kikuchi H.

  Journal of Natural Medicines 78 ( 3 ) 590 - 598 2024.06

  ISSN  13403443

  　View Summary

  Baicalin and berberine are biologically active constituents of the crude drugs Scutellaria root and Coptis rhizome/Phellodendron bark, respectively. Baicalin and berberine are reported to combine together as a 1:1 complex that forms yellow precipitates by electrostatic interaction in decoctions of Kampo formulae containing these crude drugs. However, the structural basis and mechanism for the precipitate formation of this compound–compound interaction in aqueous solution remains unclarified. Herein, we searched for berberine derivatives in the Coptis rhizome that interact with baicalin and identified the chemical structures involved in the precipitation formation. Precipitation assays showed that baicalin formed precipitates with berberine and coptisine but not with palmatine and epiberberine. Thus, the 2,3-methylenedioxy structure may be crucial to the formation of the precipitates, and electrostatic interaction is necessary but is not sufficient. In this multicomponent system experiment, palmatine formed a dissociable complex with baicalin and may competitively inhibit the formation of berberine and coptisine precipitation with baicalin. Therefore, the precipitation formed by berberine and baicalin was considered to be caused by the aggregation of the berberine–baicalin complex, and the 2,3-methylenedioxy structure is likely crucial to the aggregation of the complex. Graphic abstract: (Figure presented.)

  • Access to Document (DOI)

• Isolation and Structure Determination of New Pyrones from Dictyostelium spp. Cellular Slime Molds Coincubated with Pseudomonas spp.

  Nishimura T., Murotani T., Sasaki H., Uekusa Y., Eguchi H., Ishigaki H., Takahashi K., Kubohara Y., Kikuchi H.

  Molecules 29 ( 9 )  2024.05

  　View Summary

  Cellular slime molds are excellent model organisms in the field of cell and developmental biology because of their simple developmental patterns. During our studies on the identification of bioactive molecules from secondary metabolites of cellular slime molds toward the development of novel pharmaceuticals, we revealed the structural diversity of secondary metabolites. Cellular slime molds grow by feeding on bacteria, such as Klebsiella aerogenes and Escherichia coli, without using medium components. Although changing the feeding bacteria is expected to affect dramatically the secondary metabolite production, the effect of the feeding bacteria on the production of secondary metabolites is not known. Herein, we report the isolation and structure elucidation of clavapyrone (1) from Dictyostelium clavatum, intermedipyrone (2) from D. magnum, and magnumiol (3) from D. intermedium. These compounds are not obtained from usual cultural conditions with Klebsiella aerogenes but obtained from coincubated conditions with Pseudomonas spp. The results demonstrate the diversity of the secondary metabolites of cellular slime molds and suggest that widening the range of feeding bacteria for cellular slime molds would increase their application potential in drug discovery.

  • Access to Document (DOI)

• Anti-trypanosomal Lignans Isolated from Salvadoran Peperomia pseudopereskiifolia

  Castillo U.G., Uekusa Y., Nishimura T., Kiuchi F., Martínez M.L., Menjívar J., Nakajima-Shimada J., Núñez M.J., Kikuchi H.

  Journal of Natural Products 87 ( 4 ) 1067 - 1074 2024.04

  ISSN  01633864

  　View Summary

  A search for anti-trypanosomal natural compounds from plants collected in El Salvador, a country particularly endemic for Chagas disease, resulted in the isolation of five lignan-type compounds (1-5) from Peperomia pseudopereskiifolia. The lignan derivatives 1, 2, and 4 are new. Their absolute configuration was determined by chemical derivatization. Compounds 1, 5, 6, and 8 exhibited anti-trypanosomal activity against the amastigote form of T. cruzi comparable to that of the existing drug benznidazole.

  • Access to Document (DOI)

• Capability of a large bacterial artificial chromosome clone harboring multiple biosynthetic gene clusters for the production of diverse compounds

  Kudo K., Nishimura T., Izumikawa M., Kozone I., Hashimoto J., Fujie M., Suenaga H., Ikeda H., Satoh N., Shin-ya K.

  Journal of Antibiotics (Journal of Antibiotics)  77 ( 5 ) 288 - 298 2024

  ISSN  00218820

  　View Summary

  The biosynthetic gene clusters (BGCs) for the macrocyclic lactone-based polyketide compounds are extremely large-sized because the polyketide synthases that generate the polyketide chains of the basic backbone are of very high molecular weight. In developing a heterologous expression system for the large BGCs amenable to the production of such natural products, we selected concanamycin as an appropriate target. We obtained a bacterial artificial chromosome (BAC) clone with a 211-kb insert harboring the entire BGC responsible for the biosynthesis of concanamycin. Heterologous expression of this clone in a host strain, Streptomyces avermitilis SUKA32, permitted the production of concanamycin, as well as that of two additional aromatic polyketides. Structural elucidation identified these additional products as ent-gephyromycin and a novel compound that was designated JBIR-157. We describe herein sequencing and expression studies performed on these BGCs, demonstrating the utility of large BAC clones for the heterologous expression of cryptic or near-silent loci.

  • Access to Document (DOI)

• Synthesis of a Library of Terpenoid Alkaloid–Like Compounds Containing Medium-Sized Rings via Reconstruction of the Humulene Skeleton

  Nishimura T., Shiga K., Sekiya M., Sugawara A., Yonezawa T., Kikuchi H.

  Chemistry - A European Journal 30 ( 48 )  2024

  ISSN  09476539

  　View Summary

  The construction of a chemical library based on natural products is a promising method for the synthesis of natural product-like compounds. In this study, we synthesized a terpenoid alkaloid-like compound library based on the humulene skeleton. Our strategy, which enables access to diverse ring systems such as 11-membered monocyclic, oxabicyclic, and medium-sized aza ring-containing scaffolds, involves the introduction of a nitrogen atom, an intermolecular C−O bond formation via Lewis acid-mediated epoxide-opening transannulation, and a ring-reconstruction strategy based on olefin metathesis. A cheminformatics analysis based on their structural and physicochemical properties revealed that the synthesized compounds have high three-dimensionality and high natural product likeness scores but with structural novelty. The usefulness of the terpenoid alkaloid-like compound library for drug discovery and the accessibility to structure-activity relationship studies were validated by performing an assay for osteoclast-specific tartrate-resistant acid phosphatase activity, resulting in the identification of a seed compound for bone-resorptive diseases such as osteoporosis.

  • Access to Document (DOI)

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Reviews, Commentaries, etc. 【 Display / hide 】

Reviews, Commentaries, etc. 【 Display / hide 】

• 設計図を書き換えて難培養微生物由来化合物の生産が可能に!

  西村 壮央

  ファルマシア (公益社団法人日本薬学会)  60 ( 10 ) 966 - 966 2024.10

  Article, review, commentary, editorial, etc. (scientific journal), Single Work, Lead author,  ISSN  0014-8601

  　View Summary

  植物から得られた生物活性分子のなかには，植物に共生する微生物が真の生産者である場合がある．このような微生物の多くは，特定の共生環境でのみ生育が可能で，一般的な実験室環境下では培養が困難であり，工業生産などへの応用が難しい．Kudoらは，in vitro Cas9反応とバクテリア人工染色体(bacterial artificial chromosome: BAC)上でのギブソンアセンブリーを応用し，相同性が高い配列が繰り返されるI型モジュール型ポリケチド合成酵素遺伝子の標的領域を制約なく編集できる革新的な技術「in vitroモジュール編集」を報告している．本技術を用いて天然物の設計図とも言える生合成遺伝子を編集し，異種発現ホストに発酵生産させることができれば，自由にデザインされた化合物の生産が可能になると期待できる．本稿では，培養困難な微生物由来化合物生産における課題の解決策の1つとして，in vitroモジュール編集を活用したFR900359の生産に関する文献を紹介する．

  • Access to Document (DOI)

Presentations 【 Display / hide 】

Presentations 【 Display / hide 】

• Brefeldin Aの構造を基盤とした環状天然物の構造多様化戦略

  西村壮央, 志賀皓介, 佐藤由希, 安高賢, 植草義徳, 菊地晴久

  第65回天然有機化合物討論会 (東京大学) , 

  2023.09

  , 

  Poster presentation, 日本化学会、日本薬学会、日本農芸化学会

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

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

• 2023年度　武田科学振興財団　薬学系研究助成

  2023.08

  -

  2028.03

  武田科学振興財団, 薬学系研究助成, Research grant, Principal investigator

• 伸長型テルペノイド-ポリケチドハイブリッド型中分子化合物の創出

  2023.04

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  2026.03

  若手研究, Principal investigator

• Construction of Mid-Size Molecule Library based on the Natural Product Re-Construction Strategy

  2022.08

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  2024.03

  MEXT,JSPS, Grant-in-Aid for Scientific Research, 研究活動スタート支援, Principal investigator

• ホクト生物科学振興財団　研究助成

  2022.04

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  2023.03

  ホクト生物科学振興財団, 研究助成, Research grant, Principal investigator

Courses Taught 【 Display / hide 】

Courses Taught 【 Display / hide 】

• STUDY OF MAJOR FIELD: (NATURAL MEDICINES)

  2024

• SEMINAR: (NATURAL MEDICINES)

  2024

• RESEARCH FOR BACHELOR'S THESIS 1

  2024

• PHARMACOGNOSY LABORATORY COURSE

  2024

• PHARMACOGNOSY 2

  2024

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Memberships in Academic Societies 【 Display / hide 】

Memberships in Academic Societies 【 Display / hide 】

• 日本生薬学会, 

  2023.08

  -

  Present

• 日本細胞性粘菌学会, 

  2022.09

  -

  Present

• 日本薬学会, 

  2016.04

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  Present