博士（薬科学）, 京都大学大学院, Mar. 2017

microED

細菌間相互作用

genome mining

membrane vesicle

cryptic biosynthetic gene cluster

Chemical Biology

Natural Product Chemistry

Life Science, Environmental and natural pharmaceutical resources

Life Science, Applied microbiology, NaturalProductChemistry

Bachelor's degree program, School of Pharmaceutical Sciences and Pharmacy

Master's degree program, Graduate School of Life Science

Doctoral (PhD) degree program, Graduate School of Life Science

Jul. 2024, 天然物化学談話会, 天然物化学談話会奨励賞
休眠遺伝子由来天然物の探索基盤の構築とその応用

Nov. 2023, Japan Symposium of Microbial Ecology & Asian Symposium of Microbial Ecology, Excellent Poster Award

Jun. 2022, 日本薬学会 生薬天然物部会, 生薬天然物部会奨励研究賞
休眠遺伝子活性化による新規天然物探索系の構築とそのメカニズム解析

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, 89, 4, 1362, 1369, American Chemical Society (ACS), 15 Apr. 2026, [Peer-reviewed], [Corresponding author]
Scientific journal

Teleocidin Analogs Isolated from Streptomyces eurocidicus as Membrane-Vesicle-Regulated Natural Products
Aya Yoshimura; Ryusuke Nakada; Toshiyuki Wakimoto
Chemical and Pharmaceutical Bulletin, 73, 478, 483, 22 May 2025, [Peer-reviewed], [Lead author, Corresponding author]
Scientific journal

Harnessing membrane vesicles to activate silent bacterial metabolite production
Aya Yoshimura; Toshiyuki Wakimoto
Methods in Enzymology, 2025, [Peer-reviewed], [Lead author, Corresponding author]

New variochelins from soil-isolated Variovorax sp. H002
Jabal Rahmat Haedar; Aya Yoshimura; Toshiyuki Wakimoto
Beilstein Journal of Organic Chemistry, 02 Apr. 2024, [Peer-reviewed]
Scientific journal

Five New Analogs of Streptogramin Antibiotic Viridogrisein Isolated from Streptomyces niveoruber
Aya Yoshimura; Takumi Honda; Toshiyuki Wakimoto
Chemical and Pharmaceutical Bulletin, 72, 1, 80, 85, Pharmaceutical Society of Japan, 18 Jan. 2024, [Peer-reviewed], [Lead author, Corresponding author]
Scientific journal

Membrane‐Vesicle‐Mediated Interbacterial Communication Activates Silent Secondary Metabolite Production
Aya Yoshimura; Rio Saeki; Ryusuke Nakada; Shota Tomimoto; Takahiro Jomori; Keisuke Suganuma; Toshiyuki Wakimoto
Angewandte Chemie International Edition, Wiley, 14 Jul. 2023, [Peer-reviewed], [Lead author]
Scientific journal

Amphiol, an Antifungal Fungal Pigment from Pseudogymnoascus sp. PF1464
Kohei Fujita; Misa Ikuta; Shinichi Nishimura; Ryosuke Sugiyama; Aya Yoshimura; Hideaki Kakeya
Journal of Natural Products, 84, 4, 986, 992, American Chemical Society (ACS), 23 Apr. 2021, [Peer-reviewed], [International Magazine]
English, Scientific journal, An antifungal metabolite, designated amphiol (1), was isolated from the culture broth of the fungus Pseudogymnoascus sp. PF1464. It exists as a mixture of inseparable tautomers, an acetal form and a keto form. The chemical structure was determined by spectroscopic analyses and chemical derivatization. Amphiol (1) showed antifungal but not antibacterial activities, while yeast mutant cells lacking ergosterol biosynthetic genes were less sensitive, implying a fungal specific, membrane-related mechanism of action.

Unlocking Cryptic Metabolites with Mass Spectrometry-Guided Transposon Mutant Selection
Aya Yoshimura; Brett C. Covington; Étienne Gallant; Chen Zhang; Anran Li; Mohammad Seyedsayamdost
ACS Chemical Biology, 15, 10, 2766, 2774, American Chemical Society ({ACS}), 16 Oct. 2020, [Peer-reviewed], [Lead author]
English, Scientific journal

Reporter‐Guided Transposon Mutant Selection for Activation of Silent Gene Clusters in Burkholderia thailandensis
Dainan Mao*; Aya Yoshimura*; Rurun Wang; Mohammad Seyedsayamdost
ChemBioChem, 21, 13, 1826, 1831, Wiley, Jul. 2020, [Peer-reviewed], [Lead author]
English, Scientific journal

Multi-Omic Analyses Provide Links between Low-Dose Antibiotic Treatment and Induction of Secondary Metabolism in Burkholderia thailandensis
Anran Li*; Dainan Mao*; Aya Yoshimura*; Paul C. Rosen; W. Lance Martin; Étienne Gallant; Martin Wühr; Mohammad R. Seyedsayamdost
mBio, 11, 1, American Society for Microbiology, 25 Feb. 2020, [Peer-reviewed], [Lead author]
English, Scientific journal,
Low doses of antibiotics can trigger secondary metabolite biosynthesis in bacteria, but the underlying mechanisms are generally unknown. We sought to better understand this phenomenon by studying how the antibiotic trimethoprim activates the synthesis of the virulence factor malleilactone in Burkholderia thailandensis. Using transcriptomics, quantitative multiplexed proteomics, and primary metabolomics, we systematically mapped the changes induced by trimethoprim. Surprisingly, even subinhibitory doses of the antibiotic resulted in broad transcriptional and translational alterations, with ∼8.5% of the transcriptome and ∼5% of the proteome up- or downregulated >4-fold. Follow-up studies with genetic-biochemical experiments showed that the induction of malleilactone synthesis can be sufficiently explained by the accumulation of methionine biosynthetic precursors, notably homoserine, as a result of inhibition of the folate pathway. Homoserine activated the malleilactone gene cluster via the transcriptional regulator MalR and gave rise to a secondary metabolome which was very similar to that generated by trimethoprim. Our work highlights the expansive changes that low-dose trimethoprim induces on bacterial physiology and provides insights into its stimulatory effect on secondary metabolism.


IMPORTANCE The discovery of antibiotics ranks among the most significant accomplishments of the last century. Although the targets of nearly all clinical antibiotics are known, our understanding regarding their natural functions and the effects of subinhibitory concentrations is in its infancy. Stimulatory rather than inhibitory functions have been attributed to low-dose antibiotics. Among these, we previously found that antibiotics activate silent biosynthetic genes and thereby enhance the metabolic output of bacteria. The regulatory circuits underlying this phenomenon are unknown. We take a first step toward elucidating these circuits and show that low doses of trimethoprim (Tmp) have cell-wide effects on the saprophyte Burkholderia thailandensis. Most importantly, inhibition of one-carbon metabolic processes by Tmp leads to an accumulation of homoserine, which induces the production of an otherwise silent cytotoxin via a LuxR-type transcriptional regulator. These results provide a starting point for uncovering the molecular basis of the hormetic effects of antibiotics.

Isolation, Structure Elucidation, and Conformational Regulation of Myropeptins, Lipopeptides from the Fungus Myrothecium roridum
Aya Yoshimura; Shinichi Nishimura; Takehiro Suzuki; Akira Hattori; Naoshi Dohmae; Taira Kato; Hideaki Kakeya
Organic Letters, 21, 18, 7524, 7528, American Chemical Society ({ACS}), 20 Sep. 2019, [Peer-reviewed], [Lead author]
English, Scientific journal

ChemInform Abstract: Structure Elucidation of Verucopeptin, a HIF-1 Inhibitory Polyketide-Hexapeptide Hybrid Metabolite from an Actinomycete.
Aya Yoshimura; Shinichi Nishimura; Saori Otsuka; Akira Hattori; Hideaki Kakeya
ChemInform, 47, 12, no, no, Wiley, 03 Mar. 2016, [Lead author]
Scientific journal

Structure Elucidation of Verucopeptin, a HIF-1 Inhibitory Polyketide–Hexapeptide Hybrid Metabolite from an Actinomycete
Aya Yoshimura; Shinichi Nishimura; Saori Otsuka; Akira Hattori; Hideaki Kakeya
Organic Letters, 17, 21, 5364, 5367, 06 Nov. 2015, [Peer-reviewed], [Lead author]
English, Scientific journal

Prediction and Determination of the Stereochemistry of the 1,3,5-Trimethyl-Substituted Alkyl Chain in Verucopeptin, a Microbial Metabolite
Aya Yoshimura; Shinji Kishimoto; Shinichi Nishimura; Saori Otsuka; Yuki Sakai; Akira Hattori; Hideaki Kakeya
The Journal of Organic Chemistry, 79, 15, 6858, 6867, 01 Aug. 2014, [Peer-reviewed], [Lead author]
English, Scientific journal

細菌のメンブレンベシクルを利用した休眠遺伝子活性化とその応用
ファルマシア, 2025

小胞に乗った天然物を介した微生物間コミュニケーション
化学と生物, Oct. 2024

細胞外膜小胞を介した異種菌間相互作用が生産誘導する天然有機化合物
バイオサイエンスとインダストリー, Feb. 2024

細胞外膜小胞を介した異種菌間相互作用は二次代謝産物の生産を誘導する
微生物生態学会誌, Jan. 2024

Unlocking silent natural products through membrane vesicles-mediated bacterial communication
PacifiChem 2025, Dec. 2025
[Invited]

細胞外膜小胞と二次代謝産物を介した細菌間コミュニケーション
第77回日本生物工学会, Sep. 2025
[Invited]

生物活性に着目したゲノムマイニングによる二次代謝産物探索
第77回日本生物工学会, Sep. 2025
[Invited]

Unlocking silent natural products: Strategies and Applications
IMB seminar in University of Queensland, Aug. 2025
[Invited]

Unlocking silent natural products: Strategies and Applications
IBG seminar in Griffith University, Aug. 2025
[Invited]

Natural Product Discovery Using Bacterial Membrane Vesicles in the Post Genomic Era
Singapore Symposium on Natural Products and Biosynthetic Enzymes, Jul. 2025
[Invited]

細菌間相互作用のメディエーターとして働く二次代謝産物の探索
環境バイオテクノロジー学会2025年度大会, Jul. 2025
[Invited]

Membrane vesicles carrying natural products mediate interbacterial communication
VAAM Symposium Biology of Bacterial Natural Producers, Oct. 2024, English, Invited oral presentation
[Invited]

休眠遺伝子の活性化による天然物探索とその応用
横浜市立大学教室セミナー, Oct. 2024, Public discourse
[Invited]

細胞外小胞と二次代謝産物が仲介する細菌間相互作用
バイオインダストリー協会 発酵と代謝研究会, Jul. 2024, Invited oral presentation
[Invited]

細菌が放出する細胞外膜小胞が生産誘導する天然物に関する研究
日本農芸化学会2024年度大会, Mar. 2024, Invited oral presentation
[Invited]

Unlocking Silent Secondary Metabolites with Membrane Vesicle Mediated Interbacterial Communication
Marine Natural Products Gordon Research Conference, Mar. 2024, English, Invited oral presentation
[Invited]

細胞外膜小胞と二次代謝産物を介する異種細菌間コミュニケーション様式
第15回化学生態学研究会, Jun. 2023, Invited oral presentation
[Invited]

休眠遺伝子活性化による新規天然物探索基盤の構築とそのメカニズム解析
日本薬学会第143年会, Mar. 2023, Invited oral presentation
[Invited]

Discovery of cryptic metabolites by a bacterial elicitor
The 53rd Annual Meeting Society for Pharmacognosy, Nov. 2022, English, Invited oral presentation
[Invited]

微生物由来メンブレンベシクルが生産誘導する天然物の探索
第23回 天然薬物の開発と応用シンポジウム, Oct. 2021, Invited oral presentation
[Invited]

モノトリから始める天然物化学研究
天然物化学談話会2021オンライン特別企画, Sep. 2021, Invited oral presentation
[Invited]

天然物化学特論, 2024年, 修士課程, 生命科学院

有機化学実習Ⅲ, 2024年, 学士課程, 薬学部

有機化学実習Ⅳ, 2024年, 学士課程, 薬学部

ドラッグデザイン演習, 2024年, 学士課程, 薬学部

有機化学Ⅵ, 2024年, 学士課程, 薬学部

物質生産最大化を指向した複合微生物系デザイン戦略
創発的研究支援事業
2025 - 2032
JST, 科学技術振興機構

休眠遺伝子の選択的覚醒に基づく天然物探索戦略
科学研究費助成事業
Apr. 2026 - Mar. 2030
吉村 彩
日本学術振興会, 基盤研究(B), 北海道大学, Principal investigator, 26K02176

小分子メディエーターを活用した複合微生物系制御技術の創出
ALCA-Next グリーンバイオテクノロジー
2025 - 2028
JST, 科学技術振興機構

モジュラー型酵素の見落とされてきた立体化学制御機構の解明
学術変革領域研究A 公募研究
Apr. 2025 - Mar. 2027
JSPS, Principal investigator

多様な細胞外膜小胞の天然物生産誘導メカニズム解明による天然物探索基盤の構築
科学研究費助成事業
01 Apr. 2023 - 31 Mar. 2026
吉村 彩
近年の飛躍的なシーケンス・バイオインフォマティクス解析技術の発展により、細菌ゲノム中には通常の培養条件では発現しない天然物の生合成遺伝子クラスター（休眠遺伝子）が多く存在することが明らかになってきた。それら休眠遺伝子の活性化により天然物の構造多様性の拡張が期待できる。ところが現在、その活性化機構はほとんどの遺伝子について不明である。本研究では休眠遺伝子の活性化機構・方法を解明し、天然物探索基盤の確立を目指す。これまでに申請者はBurkholderia multivorans由来の細胞外膜小胞（MVs）が異種細菌の天然物生産を促進させる現象を見出している。本研究では当該現象の普遍性を検証し、MVsによる天然物生産誘導法を深化・発展させる。
これまでに天然物生産誘導能を示すMVsを放出する細菌種を所属研究室保有のグラム陰性菌ライブラリーから探索した。その結果、天然物生産を促進するMVsを多量に生産する細菌種を7株見出した。それらのうち3株由来のMVsを約50細菌種に添加し、MVs添加時にのみ生産される天然物をLC-MSにて探索した。それぞれのMVsごとに生産誘導する代謝物プロファイルは異なっており、様々なMVsを添加して細菌を培養することが様々な天然物の獲得に重要であることが示唆された。実際に、ヒットした代謝物のいくつかは単離・構造決定し、新規天然物を含む4つの天然物を3菌株から見出した。
日本学術振興会, 若手研究, 北海道大学, 23K14368

細菌由来小分子メディエーターを活用した細菌叢制御技術の創出
ALCA-Next グリーンバイオテクノロジー
Sep. 2024 - Mar. 2026
JST, Principal investigator

多様な細胞外膜小胞の天然物生産誘導メカニズム解明による天然物探索基盤の構築
若手研究
Apr. 2023 - Mar. 2026
JSPS, 北海道大学, Principal investigator, 23K1436803

Studies on bacterial cell-to-cell communication through membrane vesicles and secondary metabolites
ACT-X Environments and Biotechnology
Oct. 2022 - Mar. 2025
JST, Japan Science and Technology Agency, Principal investigator

休眠遺伝子覚醒機構の解明と新規天然物探索基盤の確立
若手研究
Apr. 2020 - Mar. 2023
JSPS, 若手研究, 北海道大学, Principal investigator