論文 - 詳細
| RRC ID | 87405 |
|---|---|
| 著者 | Ujie Y, Saito S, Iwata C, Kuwahara R, Kishimoto S, Watanabe K, Goto Y, Ogawa K, Hara Y, Kusuya Y, Takahashi H, Yaguchi T, Ishibashi M, Arai MA. |
| タイトル | Host-Pathogen Interaction Activated Biosynthesis of Natural Products. |
| ジャーナル | J Nat Prod |
| Abstract |
The way immune cells attack pathogenic microorganisms might trigger pathogens to produce compounds that promote their survival. Based on this idea, we constructed a coculture system of pathogenic fungi and immune cells and isolated fumigatinolactone (1) as a new natural product by coculture of Aspergillus fumigatus IFM 60237 with RAW264 mouse macrophage-like cells. Fumigatinolactone (1) was produced via a nonenzymatic coupling reaction between fumigatin (4) and a new type of intermediate fumarylazlactone (5). An investigation of the interaction mechanism between the fungi and cells revealed that the survival interaction between pathogen and immune cells played key roles. Surprisingly, fungi showed a response to nitric oxide (NO), which was produced by macrophages, resulting in the production of 4. In addition, an iron starvation condition triggered the production of 5. Finally, 1 was obtained by these two mechanisms. Furthermore, compounds 1-4, particularly 4, showed inhibition of NO production from RAW264, which might be a defense action for macrophage by fungi. This is the first example of elucidation of interaction mechanisms between pathogen and immune cells for activation of silent genes to produce a new compound. These findings suggest that host-pathogen survival interaction may increase the production of secondary metabolites from fungi. |
| 巻・号 | 88(9) |
| ページ | 2204-2215 |
| 公開日 | 2025-9-26 |
| DOI | 10.1021/acs.jnatprod.5c00776 |
| PMID | 40874357 |
| MeSH | Animals Aspergillus fumigatus* / chemistry Aspergillus fumigatus* / metabolism Biological Products* / chemistry Biological Products* / metabolism Biological Products* / pharmacology Host-Pathogen Interactions* Macrophages / metabolism Mice Molecular Structure Nitric Oxide / biosynthesis RAW 264.7 Cells |
| IF | 3.782 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 4 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 病原真核微生物 | Asprtgillus fumigatus IFM 60237 |
| ヒト・動物細胞 | RAW 264(RCB0535) J774.1(RCB0434) 293(RCB1637) |