Identification of Novel α-Pyrones from Conexibacter woesei Serving as Sulfate Shuttles

ACS Chem Biol. 2019 Sep 20;14(9):1972-1980. doi: 10.1021/acschembio.9b00455. Epub 2019 Aug 27.

Abstract

Pyrones comprise a structurally diverse class of compounds. Although they are widespread in nature, their specific physiological functions remain unknown in most cases. We recently described that triketide pyrones mediate the sulfotransfer in caprazamycin biosynthesis. Herein, we report the identification of conexipyrones A-C, three previously unrecognized tetra-substituted α-pyrones, from the soil actinobacterium Conexibacter woesei. Insights into their biosynthesis via a type III polyketide synthase were obtained by feeding studies using isotope-enriched precursors. In vitro assays employing the genetically associated 3'-phosphoadenosine-5'-phosphosulfate (PAPS)-dependent sulfotransferase CwoeST revealed conexipyrones as the enzymes' genuine sulfate acceptor substrates. Furthermore, conexipyrones were determined to function as sulfate shuttles in a two-enzyme assay, because their sulfated derivatives were accepted as donor molecules by the PAPS-independent arylsulfate sulfotransferase (ASST) Cpz4 to yield sulfated caprazamycin intermediates.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actinobacteria / chemistry*
  • Arylsulfotransferase / metabolism
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Phosphoadenosine Phosphosulfate / metabolism
  • Polyketide Synthases / genetics
  • Pyrones / isolation & purification
  • Pyrones / metabolism*
  • Streptomyces coelicolor / genetics
  • Sulfuric Acid Esters / metabolism*

Substances

  • Bacterial Proteins
  • Pyrones
  • Sulfuric Acid Esters
  • Phosphoadenosine Phosphosulfate
  • Polyketide Synthases
  • Arylsulfotransferase
  • arylsulfate sulfotransferase

Supplementary concepts

  • Conexibacter woesei