Please use this identifier to cite or link to this item: doi:10.22028/D291-28649
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Title: CYP109E1 is a novel versatile statin and terpene oxidase from Bacillus megaterium
Author(s): Putkaradze, Natalia
Litzenburger, Martin
Abdulmughni, Ammar
Milhim, Mohammed
Brill, Elisa
Hannemann, Frank
Bernhardt, Rita
Language: English
Title: Applied microbiology and biotechnology
Volume: 101
Issue: 23-24
Startpage: 8379
Endpage: 8393
Publisher/Platform: Springer
Year of Publication: 2019
Publikation type: Journal Article
Abstract: CYP109E1 is a cytochrome P450 monooxygenase from Bacillus megaterium with a hydroxylation activity for testosterone and vitamin D3. This study reports the screening of a focused library of statins, terpene-derived and steroidal compounds to explore the substrate spectrum of this enzyme. Catalytic activity of CYP109E1 towards the statin drug-precursor compactin and the prodrugs lovastatin and simvastatin as well as biotechnologically relevant terpene compounds including ionones, nootkatone, isolongifolen-9-one, damascones, and β-damascenone was found in vitro. The novel substrates induced a type I spin-shift upon binding to P450 and thus permitted to determine dissociation constants. For the identification of conversion products by NMR spectroscopy, a B. megaterium whole-cell system was applied. NMR analysis revealed for the first time the ability of CYP109E1 to catalyze an industrially highly important reaction, the production of pravastatin from compactin, as well as regioselective oxidations generating drug metabolites (6'β-hydroxy-lovastatin, 3'α-hydroxy-simvastatin, and 4″-hydroxy-simvastatin) and valuable terpene derivatives (3-hydroxy-α-ionone, 4-hydroxy-β-ionone, 11,12-epoxy-nootkatone, 4(R)-hydroxy-isolongifolen-9-one, 3-hydroxy-α-damascone, 4-hydroxy-β-damascone, and 3,4-epoxy-β-damascone). Besides that, a novel compound, 2-hydroxy-β-damascenone, produced by CYP109E1 was identified. Docking calculations using the crystal structure of CYP109E1 rationalized the experimentally observed regioselective hydroxylation and identified important amino acid residues for statin and terpene binding.
DOI of the first publication: 10.1007/s00253-017-8552-6
URL of the first publication: https://doi.org/10.1007/s00253-017-8552-6
Link to this record: hdl:20.500.11880/27679
http://dx.doi.org/10.22028/D291-28649
ISSN: 0175-7598
1432-0614
Date of registration: 6-Sep-2019
Faculty: NT - Naturwissenschaftlich- Technische Fakultät
Department: NT - Biowissenschaften
Collections:UniBib – Die Universitätsbibliographie

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