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 】

• 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)   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)

• A novel oxazole-containing tetraene compound, JBIR-159, produced by heterologous expression of the cryptic trans-AT type polyketide synthase biosynthetic gene cluster

  Hashimoto T., Hashimoto J., Kagaya N., Nishimura T., Suenaga H., Nishiyama M., Kuzuyama T., Shin-ya K.

  The Journal of Antibiotics （Journal of Antibiotics)  74 （ 5 ） 354 - 358 2021

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

  　View Summary

  Using genome mining approach, we identified a novel biosynthetic gene cluster containing trans-AT type PKS genes from Streptomyces versipellis 4083-SVS6. A bacterial artificial chromosome (BAC) clone, pKU503JL68_PN1_P10-C12, accommodating the entire biosynthetic gene cluster was obtained from a BAC library. Heterologous expression of the biosynthetic gene cluster in Streptomyces lividans TK23 led to the production of a novel polyene compound, JBIR-159. We report herein the biosynthetic gene cluster for JBIR-159, and the heterologous expression, isolation, structure determination and a brief biological activity.

  • Access to Document (DOI)

• JBIR-155, a Specific Class D β-Lactamase Inhibitor of Microbial Origin

  Nishimura T., Kawahara T., Kagaya N., Ogura Y., Takikawa H., Suenaga H., Adachi M., Hirokawa T., Doi T., Shin-Ya K.

  Organic Letters （Organic Letters)  23 （ 11 ） 4415 - 4419 2021

  Research paper (scientific journal), Joint Work, Lead author, Accepted,  ISSN  15237060

  　View Summary

  We discovered JBIR-155 as a novel specific class D β-lactamase inhibitor from Streptomyces polymachus SoB100815Hv02. JBIR-155 consists of a 6-oxabicyclo[3.2.0]heptan-7-one skeleton and a long unsaturated alkyl chain moiety of which absolute configuration was determined by spectroscopic data, modified Mosher's method, and analyses of the relative configuration of chemically modified derivative. JBIR-155 specifically exhibited inhibitory activity against the class D β-lactamase, with an IC50 value of 0.36 μM.

  • Access to Document (DOI)

• Hemiacetal-less rapamycin derivatives designed and produced by genetic engineering of a type I polyketide synthase

  Kudo K., Nishimura T., Kozone I., Hashimoto J., Kagaya N., Suenaga H., Ikeda H., Shin-ya K.

  Scientific Reports （Scientific Reports)  11 （ 1 ） 9944 2021

  Research paper (scientific journal), Joint Work, Accepted

  　View Summary

  Engineering polyketide synthases is one of the most promising ways of producing a variety of polyketide derivatives. Exploring the undiscovered chemical space of this medicinally important class of middle molecular weight natural products will aid in the development of improved drugs in the future. In previous work, we established methodology designated ‘module editing’ to precisely manipulate polyketide synthase genes cloned in a bacterial artificial chromosome. Here, in the course of investigating the engineering capacity of the rapamycin PKS, novel rapamycin derivatives 1–4, which lack the hemiacetal moiety, were produced through the heterologous expression of engineered variants of the rapamycin PKS. Three kinds of module deletions in the polyketide synthase RapC were designed, and the genetically engineered vectors were prepared by the in vitro module editing technique. Streptomyces avermitilis SUKA34 transformed with these edited PKSs produced new rapamycin derivatives. The planar structures of 1–4 established based on 1D and 2D NMR, ESI–TOF–MS and UV spectra revealed that 2 and 3 had skeletons well-matched to the designs, but 1 and 4 did not. The observations provide important insights into the mechanisms of the later steps of rapamycin skeletal formation as well as the ketone-forming oxygenase RapJ.

  • Access to Document (DOI)

• In vitro Cas9-assisted editing of modular polyketide synthase genes to produce desired natural product derivatives

  Nature Communications 11 （ 1 ） 4022 2020

  Research paper (scientific journal), Joint Work, Accepted

  • Access to Document (DOI)

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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

  -

  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

  -

  Present