論文 - 詳細
| RRC ID | 74394 |
|---|---|
| 著者 | Ueoka R, Sondermann P, Leopold-Messer S, Liu Y, Suo R, Bhushan A, Vadakumchery L, Greczmiel U, Yashiroda Y, Kimura H, Nishimura S, Hoshikawa Y, Yoshida M, Oxenius A, Matsunaga S, Williamson RT, Carreira EM, Piel J. |
| タイトル | Genome-based discovery and total synthesis of janustatins, potent cytotoxins from a plant-associated bacterium. |
| ジャーナル | Nat Chem |
| Abstract |
Host-associated bacteria are increasingly being recognized as underexplored sources of bioactive natural products with unprecedented chemical scaffolds. A recently identified example is the plant-root-associated marine bacterium Gynuella sunshinyii of the chemically underexplored order Oceanospirillales. Its genome contains at least 22 biosynthetic gene clusters, suggesting a rich and mostly uncharacterized specialized metabolism. Here, in silico chemical prediction of a non-canonical polyketide synthase cluster has led to the discovery of janustatins, structurally unprecedented polyketide alkaloids with potent cytotoxicity that are produced in minute quantities. A combination of MS and two-dimensional NMR experiments, density functional theory calculations of 13C chemical shifts and semiquantitative interpretation of transverse rotating-frame Overhauser effect spectroscopy data were conducted to determine the relative configuration, which enabled the total synthesis of both enantiomers and assignment of the absolute configuration. Janustatins feature a previously unknown pyridodihydropyranone heterocycle and an unusual biological activity consisting of delayed, synchronized cell death at subnanomolar concentrations. |
| 巻・号 | 14(10) |
| ページ | 1193-1201 |
| 公開日 | 2022-10-1 |
| DOI | 10.1038/s41557-022-01020-0 |
| PII | 10.1038/s41557-022-01020-0 |
| PMID | 36064972 |
| PMC | PMC7613652 |
| MeSH | Bacteria / metabolism Biological Products* / chemistry Cytotoxins / metabolism Cytotoxins / pharmacology Polyketide Synthases / metabolism Polyketides* / metabolism |
| 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 | 58 |
| 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 | |
| ヒト・動物細胞 | 3Y1 HeLa P388(RCB2776) |