Biosynthesis of a -Acetylated Tricyclic Carbazole with Antithrombotic Activity.
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| Format: | Artículo científico |
| Sprache: | en |
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Journal of natural products
2025
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| _version_ | 1868266214114983937 |
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| author | Luo, Jiaming Shen, Yaoyao Liu, Ke Hong, Li Li Yang, Ming Li, Ning Deng, Hai Lin, Hou-Wen Zhou, Yongjun |
| author_facet | Luo, Jiaming Shen, Yaoyao Liu, Ke Hong, Li Li Yang, Ming Li, Ning Deng, Hai Lin, Hou-Wen Zhou, Yongjun Luo, Jiaming Shen, Yaoyao Liu, Ke Hong, Li Li Yang, Ming Li, Ning Deng, Hai Lin, Hou-Wen Zhou, Yongjun |
| collection | PubMed - marine biology |
| contents | Biosynthesis of a -Acetylated Tricyclic Carbazole with Antithrombotic Activity. Luo, Jiaming Shen, Yaoyao Liu, Ke Hong, Li Li Yang, Ming Li, Ning Deng, Hai Lin, Hou-Wen Zhou, Yongjun Animals Acetylation Carbazoles Crystallography, X-Ray Fibrinolytic Agents Molecular Structure Streptomyces Zebrafish Acetaldehyde Tricyclic carbazoles are significant pharmacophores. Herein, heterologous expression of the carbazole-3,4-quinone () biosynthetic pathway in the chassis host J1074 yielded a previously chemosynthesized orthoquinone carbazole () and three new -acetylated carbazoles (-). Their structures were established by a combination of HR-ESI-MS, NMR, and X-ray crystallographic analysis. Compound , the deaminated precursor of and , was enzymatically synthesized, indicating the substrate tolerance of the key enzymes in the bacterial tricyclic-carbazole biosynthetic pathway. Mutagenetic analysis revealed an arylamine -acetyltransferase homologous gene required for the production of compounds -. Bioactivity analysis using the zebrafish model demonstrated that compound has significant antithrombotic activity, potentially by downregulating the genes involved in the platelet activation and coagulation cascade. These findings expand the natural strategies for structural diversification of the tricyclic carbazole alkaloids. |
| format | Artículo científico |
| id | pubmed_40262092 |
| institution | PubMed |
| language | en |
| publishDate | 2025 |
| publisher | Journal of natural products |
| record_format | pubmed |
| spellingShingle | Biosynthesis of a -Acetylated Tricyclic Carbazole with Antithrombotic Activity. Luo, Jiaming Shen, Yaoyao Liu, Ke Hong, Li Li Yang, Ming Li, Ning Deng, Hai Lin, Hou-Wen Zhou, Yongjun Animals Acetylation Carbazoles Crystallography, X-Ray Fibrinolytic Agents Molecular Structure Streptomyces Zebrafish Acetaldehyde Biosynthesis of a -Acetylated Tricyclic Carbazole with Antithrombotic Activity. Luo, Jiaming Shen, Yaoyao Liu, Ke Hong, Li Li Yang, Ming Li, Ning Deng, Hai Lin, Hou-Wen Zhou, Yongjun Animals Acetylation Carbazoles Crystallography, X-Ray Fibrinolytic Agents Molecular Structure Streptomyces Zebrafish Acetaldehyde Tricyclic carbazoles are significant pharmacophores. Herein, heterologous expression of the carbazole-3,4-quinone () biosynthetic pathway in the chassis host J1074 yielded a previously chemosynthesized orthoquinone carbazole () and three new -acetylated carbazoles (-). Their structures were established by a combination of HR-ESI-MS, NMR, and X-ray crystallographic analysis. Compound , the deaminated precursor of and , was enzymatically synthesized, indicating the substrate tolerance of the key enzymes in the bacterial tricyclic-carbazole biosynthetic pathway. Mutagenetic analysis revealed an arylamine -acetyltransferase homologous gene required for the production of compounds -. Bioactivity analysis using the zebrafish model demonstrated that compound has significant antithrombotic activity, potentially by downregulating the genes involved in the platelet activation and coagulation cascade. These findings expand the natural strategies for structural diversification of the tricyclic carbazole alkaloids. |
| title | Biosynthesis of a -Acetylated Tricyclic Carbazole with Antithrombotic Activity. |
| topic | Animals Acetylation Carbazoles Crystallography, X-Ray Fibrinolytic Agents Molecular Structure Streptomyces Zebrafish Acetaldehyde |
| url | https://pubmed.ncbi.nlm.nih.gov/40262092/ |