Novel Unspecific Peroxygenase from Truncatella angustata Catalyzes the Synthesis of Bioactive Lipid Mediators

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Rosalie König - , Brandenburg University of Technology (Autor:in)
  • Jan Kiebist - , Brandenburg University of Technology, Fraunhofer Institute for Cell Therapy and Immunology (Autor:in)
  • Johannes Kalmbach - , Brandenburg University of Technology (Autor:in)
  • Robert Herzog - , Professur für Umweltbiotechnologie (Autor:in)
  • Kai-Uwe Schmidtke - , Brandenburg University of Technology (Autor:in)
  • Harald Kellner - , Professur für Umweltbiotechnologie (Autor:in)
  • René Ullrich - , Professur für Umweltbiotechnologie (Autor:in)
  • Nico Jehmlich - , Helmholtz-Zentrum für Umweltforschung (UFZ) (Autor:in)
  • Martin Hofrichter - , Professur für Umweltbiotechnologie (Autor:in)
  • Katrin Scheibner - , Brandenburg University of Technology (Autor:in)

Abstract

Lipid mediators, such as epoxidized or hydroxylated eicosanoids (EETs, HETEs) of arachidonic acid (AA), are important signaling molecules and play diverse roles at different physiological and pathophysiological levels. The EETs and HETEs formed by the cytochrome P450 enzymes are still not fully explored, but show interesting anti-inflammatory properties, which make them attractive as potential therapeutic target or even as therapeutic agents. Conventional methods of chemical synthesis require several steps and complex separation techniques and lead only to low yields. Using the newly discovered unspecific peroxygenase TanUPO from the ascomycetous fungus Truncatella angustata, 90% regioselective conversion of AA to 14,15-EET could be achieved. Selective conversion of AA to 18-HETE, 19-HETE as well as to 11,12-EET and 14,15-EET was also demonstrated with known peroxygenases, i.e., AaeUPO, CraUPO, MroUPO, MweUPO and CglUPO. The metabolites were confirmed by HPLC-ELSD, MS1 and MS2 spectrometry as well as by comparing their analytical data with authentic standards. Protein structure simulations of TanUPO provided insights into its substrate access channel and give an explanation for the selective oxyfunctionalization of AA. The present study expands the scope of UPOs as they can now be used for selective syntheses of AA metabolites that serve as reference material for diagnostics, for structure-function elucidation as well as for therapeutic and pharmacological purposes.

Details

OriginalspracheEnglisch
Aufsatznummer1267
Seiten (von - bis)1-18
Seitenumfang18
FachzeitschriftMicroorganisms
Jahrgang10
Ausgabenummer7
PublikationsstatusVeröffentlicht - Juli 2022
Peer-Review-StatusJa

Externe IDs

ORCID /0000-0002-0026-2145/work/149204720

Schlagworte

Schlagwörter

  • biocatalysis, EETs, eicosanoids, HETEs, human drug metabolites, lipid mediators, TanUPO, unspecific peroxygenases

Bibliotheksschlagworte