Induced production, synthesis and immunomodulatory action of clostrisulfone, a diarylsulfone from Clostridium acetobutylicum.

Neuwirth T, Letzel AC, Tank C, Ishida K, Cyrulies M, Schmölz L, Lorkowski S, Hertweck C (2020) Induced production, synthesis and immunomodulatory action of clostrisulfone, a diarylsulfone from Clostridium acetobutylicum. Chemistry [In press] PubMed Open Access PDF

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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doi: 10.1002/chem.202003500 PMID: 32996646