論文 - 詳細
| RRC ID | 80987 |
|---|---|
| 著者 | Marcin Wolański, Michał Krawiec, Kay Nieselt, Tobias Schwarz, Dilek Dere, Bernhard Krismer, Carolina Cano-Prieto, Harald Gross, Jolanta Zakrzewska-Czerwińska |
| タイトル | Multiple regulators control the biosynthesis of brasilicardin inNocardia terpenica |
| Abstract |
Brasilicardin A, BraA, is a secondary metabolite produced by the bacteriumNocardia terpenica, and a promising drug due to its potent immunosuppressive activity and low cytotoxicity. Currently, a semisynthetic approach confers production of a complete compound but suffers from insufficient heterologous biosynthesis of BraA intermediates used in the chemical semi-synthesis steps leading to only lab scale quantities of the compound. A better understanding of the involved gene expression regulatory pathways within the brasilicardin biosynthetic gene cluster, Bra-BGC, is a prerequisite to further improve production titers. However, the transcriptional regulation of the Bra-BGC has only been superficially analyzed, till now.In this study, we comprehensively analyze the functions of several unstudied transcriptional regulators, KstR, SdpR and OmpR, encoded within the close vicinity of the Bra-BGC, and delve into the role of the previously described cluster-situated activator Bra12. We present, that Bra12 and the novel regulator SdpR, bind several DNA sequences located in the promoter regions of the genes essential for BraA biosynthesis. Subsequently, we demonstrate the complex regulatory network through which both regulators are capable of controlling activity of those gene promoters and thus gene expression in Bra-BGC. Furthermore, using the heterologous producer strainAmycolatopsis japonicum, we present, that Bra12 and SdpR regulators play opposite roles in brasilicardin congener biosynthesis. Finally, we propose a comprehensive model of multilevel gene expression regulation in Bra-BGC and propose the roles of locally encoded transcriptional regulators. |
| 公開日 | 2024-1-1 |
| DOI | 10.1101/2024.06.11.594307 |
| 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 | 8 |
| 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 | Nocardia terpenica IFM 0406 |