Sequestration of Guest Intermediates by Dalesconol Bioassembly Lines in Daldinia eschscholzii

Org Lett. 2017 Apr 21;19(8):2142-2145. doi: 10.1021/acs.orglett.7b00786. Epub 2017 Apr 10.

Abstract

Microbial constructions of secondary metabolites are generally biosynthetic gene cluster (BGC)-based, and the forging of different BGC-sourced intermediates tends to be overlooked. Here, we show that the dalesconol bioassembly lines in Daldinia eschscholzii can sequester guest intermediates (i.e., building blocks produced outside the dalesconol biosynthetic gene cluster) to form arrays of skeletally undescribed molecules such as (+)-dalescone A, a potent inhibitor against the NLRP3 inflammasome activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Products / chemistry*
  • Biological Products / metabolism
  • Biosynthetic Pathways
  • Cell Line
  • Humans
  • Inflammasomes / metabolism
  • Interleukin-1beta / metabolism
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Molecular Structure
  • Multigene Family
  • Polycyclic Aromatic Hydrocarbons / chemistry*
  • Polycyclic Aromatic Hydrocarbons / metabolism
  • Secondary Metabolism
  • Stereoisomerism
  • Xylariales / chemistry*
  • Xylariales / genetics
  • Xylariales / metabolism

Substances

  • Biological Products
  • Inflammasomes
  • Interleukin-1beta
  • Polycyclic Aromatic Hydrocarbons
  • dalesconol A