A Peroxygenase fromChaetomium globosumCatalyzes the Selective Oxygenation of Testosterone

Autor: Katrin Scheibner, Daniel Zänder, Jan Kiebist, René Ullrich, Kai-Uwe Schmidtke, Jörg Zimmermann, Nico Jehmlich, Martin Hofrichter, Harald Kellner
Rok vydání: 2017
Předmět:
0301 basic medicine
Stereochemistry
Chemistry
Pharmaceutical
medicine.medical_treatment
peroxidase
Chaetomium
01 natural sciences
Biochemistry
Catalysis
Mixed Function Oxygenases
hydroxylation
Steroid
oxyfunctionalization
Hydroxylation
03 medical and health sciences
chemistry.chemical_compound
Unspecific peroxygenase
epoxidation
peroxidase
hydroxylation
epoxidation
steroid
oxyfunctionalization
TU Dresden
Publishing Fund
medicine
Organic chemistry
Testosterone
Amino Acid Sequence
Molecular Biology
Chromatography
High Pressure Liquid
Full Paper
biology
Chaetomium globosum
010405 organic chemistry
Chemistry
Agrocybe
steroid
Organic Chemistry
Substrate (chemistry)
Fast protein liquid chromatography
Full Papers
biology.organism_classification
0104 chemical sciences
Turnover number
Oxygen
030104 developmental biology
ddc:540
Peroxidase
Hydroxylierung
Epoxidierung
Steriod
Oxyfunktionalisierung
TU Dresden
Publikationsfonds
Molecular Medicine
Zdroj: Chembiochem
ChemBioChem
ISSN: 1439-4227
Popis: 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.
Databáze: OpenAIRE
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