Discovery of thiazostatin D/E using UPLC-HR-MS2-based metabolomics and σ-factor engineering of Actinoplanes sp. SE50/110.
| Autor: | Schlüter L; Microbial Genomics and Biotechnology, Center for Biotechnology, Bielefeld University, Bielefeld, Germany., Hansen KØ; Department of Pharmacy, Faculty of Medicine and Health Sciences, UiT-The Arctic University of Norway, Tromsø, Norway., Isaksson J; Department of Pharmacy, Faculty of Medicine and Health Sciences, UiT-The Arctic University of Norway, Tromsø, Norway., Andersen JH; Marbio, Faculty for Fisheries, Biosciences and Economy, UiT-The Arctic University of Norway, Tromsø, Norway., Hansen EH; Marbio, Faculty for Fisheries, Biosciences and Economy, UiT-The Arctic University of Norway, Tromsø, Norway., Kalinowski J; Microbial Genomics and Biotechnology, Center for Biotechnology, Bielefeld University, Bielefeld, Germany.; Technology Platform Genomics, Center for Biotechnology, Bielefeld University, Bielefeld, Germany., Schneider YK; Marbio, Faculty for Fisheries, Biosciences and Economy, UiT-The Arctic University of Norway, Tromsø, Norway. |
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| Jazyk: | angličtina |
| Zdroj: | Frontiers in bioengineering and biotechnology [Front Bioeng Biotechnol] 2024 Nov 25; Vol. 12, pp. 1497138. Date of Electronic Publication: 2024 Nov 25 (Print Publication: 2024). |
| DOI: | 10.3389/fbioe.2024.1497138 |
| Abstrakt: | As the natural producer of acarbose, Actinoplanes sp. SE50/110 has high industrial relevance. Like most Actinobacteria, the strain carries several more putative biosynthetic gene clusters (BGCs) to produce further natural products, which are to be discovered. Applying a metabolomics-guided approach, we tentatively identified five further compounds that are produced by the strain: watasemycin, thiazostatin, isopyochelin, pulicatin, and aerugine. A comparison of the genomic context allowed the identification of the putative BGC, which is highly similar to the watasemycin biosynthetic gene cluster of Streptomyces venezuelae . In addition to the identified molecules, a thiazostatin-like compound was found. Isolation and structure elucidation with 1D and 2D NMR and HRMS were applied. The fraction containing m/z 369.0929 [M + H] + comprised two highly similar compounds identified as thiazostatin D and thiazostatin E. The compounds possessed the same phenol-thiazole-thiazole molecular scaffold as the previously reported thiazostatin and watasemycin and have anti-proliferative activity against the breast adenocarcinoma cell line MCF7 and human melanoma cell line A2058, while no activity again the non-malignant immortalized fibroblast cell line MRC-5 was observed. We further showed that the manipulation of global transcriptional regulators, with sigH ( ACSP50_0507 ) and anti-anti-σ factor coding ACSP50_0284 as an example, enabled the production manipulation of the 2-hydroxyphenylthiazoline family molecules. While the manipulation of sigH enabled the shift in the peak intensities between the five products of this pathway, ACSP50_0284 manipulation prevented their production. The production of a highly polar compound with m/z 462.1643 [M + H] + and calculated elemental composition C Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Schlüter, Hansen, Isaksson, Andersen, Hansen, Kalinowski and Schneider.) |
| Databáze: | MEDLINE |
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