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Induced Production, Synthesis, and Immunomodulatory Action of Clostrisulfone, a Diarylsulfone from Clostridium acetobutylicum
Author(s) -
Neuwirth Toni,
Letzel AnneCatrin,
Tank Cedric,
Ishida Keishi,
Cyrulies Michael,
Schmölz Lisa,
Lorkowski Stefan,
Hertweck Christian
Publication year - 2020
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202003500
Subject(s) - clostridium acetobutylicum , chemistry , natural product , nitric oxide , bacteria , biosynthesis , biochemistry , cysteine , clostridium , lipopolysaccharide , metabolism , gene , biology , enzyme , organic chemistry , genetics , butanol , ethanol , endocrinology
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 .