Details zur Publikation

Kategorie Textpublikation
Referenztyp Zeitschriften
DOI 10.3390/microorganisms10071267
Lizenz creative commons licence
Titel (primär) Novel unspecific peroxygenase from Truncatella angustata catalyzes the synthesis of bioactive lipid mediators
Autor König, R.; Kiebist, J.; Kalmbach, J.; Herzog, R.; Schmidtke, K.-U.; Kellner, H.; Ullrich, R.; Jehmlich, N. ORCID logo ; Hofrichter, M.; Scheibner, K.
Quelle Microorganisms
Erscheinungsjahr 2022
Department MOLSYB
Band/Volume 10
Heft 7
Seite von art. 1267
Sprache englisch
Topic T9 Healthy Planet
Keywords eicosanoids; lipid mediators; EETs; HETEs; unspecific peroxygenases; human drug metabolites; biocatalysis; TanUPO
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.
dauerhafte UFZ-Verlinkung
König, R., Kiebist, J., Kalmbach, J., Herzog, R., Schmidtke, K.-U., Kellner, H., Ullrich, R., Jehmlich, N., Hofrichter, M., Scheibner, K. (2022):
Novel unspecific peroxygenase from Truncatella angustata catalyzes the synthesis of bioactive lipid mediators
Microorganisms 10 (7), art. 1267 10.3390/microorganisms10071267