Induced Production, Synthesis, and Immunomodulatory Action of Clostrisulfone, a Diarylsulfone from Clostridium acetobutylicum

Chemistry. 2020 Dec 4;26(68):15855-15858. doi: 10.1002/chem.202003500. Epub 2020 Nov 3.

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.

Keywords: Griess assay; clostridia; diphenylsulfone; macrophages; tocopherol.

MeSH terms

  • Animals
  • Clostridium acetobutylicum* / chemistry
  • Clostridium acetobutylicum* / drug effects
  • Clostridium acetobutylicum* / genetics
  • Clostridium acetobutylicum* / metabolism
  • Cysteine / pharmacology
  • Immunologic Factors* / metabolism
  • Immunologic Factors* / pharmacology
  • Macrophages / drug effects
  • Mice
  • Multigene Family
  • Sulfones* / metabolism
  • Sulfones* / pharmacology

Substances

  • Immunologic Factors
  • Sulfones
  • Cysteine