Induced Production,Synthesis, and Immunomodulatory Action of Clostrisulfone,a Diarylsulfone from Clostridium acetobutylicum |
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Authors: | Toni Neuwirth Dr Anne-Catrin Letzel Cedric Tank Dr Keishi Ishida Michael Cyrulies Dr Lisa Schmölz Prof?Dr Stefan Lorkowski Prof?Dr Christian Hertweck |
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Institution: | 1. Department of Biomolecular Chemistry, Leibniz Institute for Natural Product Chemistry and Infection Biology (HKI), Beutenbergstr. 11a, 07745 Jena, Germany;2. BioPilotPlant, Leibniz Institute for Natural Product Chemistry and Infection Biology (HKI), Beutenbergstr. 11a, 07745 Jena, Germany;3. Institute of Nutritional Sciences, Friedrich Schiller University Jena, Dornburger Straße 25, 07743 Jena, Germany |
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Abstract: | The anaerobe Clostridium acetobutylicum belongs to the most important industrially used bacteria. Whereas genome mining points to a high potential for secondary metabolism in C. acetobutylicum, the functions of most biosynthetic gene clusters are cryptic. We report that the addition of supra-physiological concentrations of cysteine triggered the formation of a novel natural product, clostrisulfone ( 1 ). Its structure was fully elucidated by NMR, MS and the chemical synthesis of a reference compound. Clostrisulfone is the first reported natural product with a diphenylsulfone scaffold. A biomimetic synthesis suggests that pentamethylchromanol-derived radicals capture sulfur dioxide to form 1 . In a cell-based assay using murine macrophages a biphasic and dose-dependent regulation of the LPS-induced release of nitric oxide was observed in the presence of 1 . |
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Keywords: | clostridia diphenylsulfone Griess assay macrophages tocopherol |
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