Fungal Unspecific Peroxygenases: Heme-Thiolate Proteins That Combine Peroxidase and Cytochrome P450 Properties

  • Martin HofrichterEmail author
  • Harald Kellner
  • Marek J. Pecyna
  • René Ullrich
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 851)


Eleven years ago, a secreted heme-thiolate peroxidase with promiscuity for oxygen transfer reactions was discovered in the basidiomycetous fungus, Agrocybe aegerita. The enzyme turned out to be a functional mono-peroxygenase that transferred an oxygen atom from hydrogen peroxide to diverse organic substrates (aromatics, heterocycles, linear and cyclic alkanes/alkenes, fatty acids, etc.). Later similar enzymes were found in other mushroom genera such as Coprinellus and Marasmius. Approximately one thousand putative peroxygenase sequences that form two large clusters can be found in genetic databases and fungal genomes, indicating the widespread occurrence of such enzymes in the whole fungal kingdom including all phyla of true fungi (Eumycota) and certain fungus-like heterokonts (Oomycota). This new enzyme type was classified as unspecific peroxygenase (UPO, EC and placed in a separate peroxidase subclass. Furthermore, UPOs and related heme-thiolate peroxidases such as well-studied chloroperoxidase (CPO) represent a separate superfamily of heme proteins on the phylogenetic level. The reactions catalyzed by UPOs include hydroxylation, epoxidation, O- and N-dealkylation, aromatization, sulfoxidation, N-oxygenation, dechlorination and halide oxidation. In many cases, the product patterns of UPOs resemble those of human cytochrome P450 (P450) monooxygenases and, in fact, combine the catalytic cycle of heme peroxidases with the “peroxide shunt” of P450s. Here, an overview on UPOs is provided with focus on their molecular and catalytic properties.


Peroxidase P450 monooxygenase Heme-thiolate Compound I Hydroxylation Epoxidation Dealkylation 



We would like to thank K. Barkova, M. G. Kluge, S. Peter, C. Dolge and M. Poraj-Kobielska (TU Dresden-IHI Zittau, Germany) for still unpublished results on the catalytic properties of unspecific peroxygenases and our project partners L. Kalum and H. Lund (Novozymes A/S, Denmark) for enzyme samples as well as useful discussions. We acknowledge fruitful cooperations with the following colleagues: K. Piontek and D. Plattner (University of Freiburg, Germany) in the field of protein crystallography, X. Wang and J. T. Groves (Princeton University, USA) regarding stopped-flow techniques, and J. Atzrodt and W. Holla (Sanofi Frankfurt, Germany) in the field of drug metabolites. UPO work has been financially supported by the European Union (integrated projects Biorenew, Peroxicats and Indox), the Deutsche Bundestiftung Umwelt (DBU; projects AZ 1327 and AZ 13225) and the Bundesministerium für Forschung (BMBF, projects 0313433 and 0315877).


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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Martin Hofrichter
    • 1
    Email author
  • Harald Kellner
    • 1
  • Marek J. Pecyna
    • 1
  • René Ullrich
    • 1
  1. 1.Department of Bio- and Environmental SciencesInternational Institute Zittau, Technische Universität DresdenZittauGermany

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