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

  • Chapter
Monooxygenase, Peroxidase and Peroxygenase Properties and Mechanisms of Cytochrome P450

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 851))

Abstract

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 1.11.2.1) 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.

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Notes

  1. 1.

    EC 1.11.2 With H2O2 as acceptor, one oxygen atom is incorporated into the product.

  2. 2.

    www.chem.qmul.ac.uk/iubmb/enzyme/EC1/11/2/4.html

  3. 3.

    www.chem.qmul.ac.uk/iubmb/enzyme/EC1/11/2/2.html

  4. 4.

    Because of the discovery of many more unspecific peroxygenases, they should be systematically abbreviated by the capital letter of the genus plus the first and second letter of the epitheton and the acronym UPO: for example, AaeUPO = unspecific peroxygenase of Agrocybe aegerita.

  5. 5.

    veratryl alcohol units (compare Sect. 13.4.3)

  6. 6.

    http://www.chem.qmul.ac.uk/iubmb/enzyme/EC1/14/14/1.html

  7. 7.

    Note that in many, especially older publications on heme peroxidases, compound II is described as a (deprotonated) oxo-ferryl complex with a double bond between iron and oxygen (FeIV=O) corresponding to (v) in Fig. 13.10. In reality, both ferryl species (FeIV=O and FeIV-OH) of UPO compound II may be present as shown for CPO.

  8. 8.

    Usually, oxygen in aldehyde functionalities rapidly exchanges in water via the corresponding aldehyde hydrates, which prevents the verification of oxygen insertion, but aromatic nitro groups as in p-nitrobenzaldehyde slow down the exchange.

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Acknowledgments

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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  1. Department of Bio- and Environmental Sciences, International Institute Zittau, Technische Universität Dresden, Markt 23, Zittau, 02763, Germany

    Martin Hofrichter, Harald Kellner, Marek J. Pecyna & René Ullrich

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  1. Martin Hofrichter
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Correspondence to Martin Hofrichter .

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  1. Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, British Columbia, Canada

    Eugene G. Hrycay

  2. Fac. of Pharmaceutical Sciences, The University of British Columbia , Vancouver, British Columbia, Canada

    Stelvio M. Bandiera

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Hofrichter, M., Kellner, H., Pecyna, M.J., Ullrich, R. (2015). Fungal Unspecific Peroxygenases: Heme-Thiolate Proteins That Combine Peroxidase and Cytochrome P450 Properties. In: Hrycay, E., Bandiera, S. (eds) Monooxygenase, Peroxidase and Peroxygenase Properties and Mechanisms of Cytochrome P450. Advances in Experimental Medicine and Biology, vol 851. Springer, Cham. https://doi.org/10.1007/978-3-319-16009-2_13

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