Pityriazepin and other potent AhR ligands isolated from Malassezia furfur yeast

Nikitia Mexia, Georgios Gaitanis, Aristea Velegraki, Anatoly Soshilov, Michael S. Denison, Prokopios Magiatis

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Malassezia furfur yeast strains isolated from diseased human skin preferentially biosynthesize indole alkaloids which can be detected in the human skin and are highly potent activators of the aryl hydrocarbon receptor (AhR) and AhR-dependent gene expression. Chemical analysis of an EtOAc extract of a M. furfur strain obtained from diseased human skin and grown on l-tryptophan agar revealed several known AhR active tryptophan metabolites along with a previously unidentified compound, pityriazepin. While its structure resembled that of the known alkaloid pityriacitrin, the comprised pyridine ring had been transformed into an azepinone. The indoloazepinone scaffold of pityriazepin is extremely rare in nature and has only been reported once previously. Pityriazepin, like the other isolated compounds, was found to be a potent activator of the AhR-dependent reporter gene assay in recombinant cell lines derived from four different species, although significant species differences in relative potency were observed. The ability of pityriazepin to competitively bind to the AhR and directly stimulate AhR DNA binding classified it as a new naturally-occurring potent AhR agonist. M. furfur produces an expanded collection of extremely potent naturally occurring AhR agonists, which produce their biological effects in a species-specific manner.

Original languageEnglish (US)
Article number6923
Pages (from-to)16-20
Number of pages5
JournalArchives of Biochemistry and Biophysics
Volume571
DOIs
StatePublished - Apr 1 2015

Keywords

  • Aryl-hydrocarbon receptor
  • Indole metabolites
  • Malassezia furfur
  • Pityriacitrin
  • Pityriazepin

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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    Mexia, N., Gaitanis, G., Velegraki, A., Soshilov, A., Denison, M. S., & Magiatis, P. (2015). Pityriazepin and other potent AhR ligands isolated from Malassezia furfur yeast. Archives of Biochemistry and Biophysics, 571, 16-20. [6923]. https://doi.org/10.1016/j.abb.2015.02.023