A Peroxygenase from Chaetomium globosum Catalyzes the Selective Oxygenation of Testosterone

Article abstract of DOI:10.1002/cbic.201600677

Unspecific peroxygenases (UPO, EC 1.11.2.1) secreted by fungi open an efficient way to selectively oxyfunctionalize diverse organic substrates, including less-activated hydrocarbons, by transferring peroxide-borne oxygen. We investigated a cell-free approach to incorporate epoxy and hydroxyl functionalities directly into the bulky molecule testosterone by a novel unspecific peroxygenase (UPO) that is produced by the ascomycetous fungus Chaetomium globosum in a complex medium rich in carbon and nitrogen. Purification by fast protein liquid chromatography revealed two enzyme fractions with the same molecular mass (36 kDa) and with specific activity of 4.4 to 12 U mg^?1. Although the well-known UPOs of Agrocybe aegerita (AaeUPO) and Marasmius rotula (MroUPO) failed to convert testosterone in a comparative study, the UPO of C. globosum (CglUPO) accepted testosterone as substrate and converted it with total turnover number (TTN) of up to 7000 into two oxygenated products: the 4,5-epoxide of testosterone in β-configuration and 16α-hydroxytestosterone. The reaction performed on a 100 mg scale resulted in the formation of about 90 % of the epoxide and 10 % of the hydroxylation product, both of which could be isolated with purities above 96 %. Thus, CglUPO is a promising biocatalyst for the oxyfunctionalization of bulky steroids and it will be a useful tool for the synthesis of pharmaceutically relevant steroidal molecules.

Full text of DOI:10.1002/cbic.201600677

Accepted Article
Title: A peroxygenase from Chaetomium globosum catalyzes the
selective oxygenation of testosterone
Authors: Jan Kiebist, Kai-Uwe Schmidtke, Jörg Zimmermann, Harald
Kellner, Nico Jehmlich, René Ullrich, Daniel Zänder, Martin
Hofrichter, and Katrin Scheibner
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: ChemBioChem 10.1002/cbic.201600677
Link to VoR: http://dx.doi.org/10.1002/cbic.201600677
A Journal of
www.chembiochem.org

ChemBioChem
10.1002/cbic.201600677
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10.1002/cbic.201600677
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ChemBioChem
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ChemBioChem
10.1002/cbic.201600677
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ChemBioChem
10.1002/cbic.201600677
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ChemBioChem
10.1002/cbic.201600677
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ChemBioChem
10.1002/cbic.201600677
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ChemBioChem
10.1002/cbic.201600677
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ChemBioChem
10.1002/cbic.201600677
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10.1002/cbic.201600677
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10.1002/cbic.201600677
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ChemBioChem
10.1002/cbic.201600677
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ChemBioChem
10.1002/cbic.201600677
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This article is protected by copyright. All rights reserved.

ChemBioChem
10.1002/cbic.201600677
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This article is protected by copyright. All rights reserved.

ChemBioChem
10.1002/cbic.201600677
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ChemBioChem
10.1002/cbic.201600677
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