Please use this identifier to cite or link to this item: doi:10.22028/D291-29473
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Title: Novel approach to improve progesterone hydroxylation selectivity by CYP106A2 via rational design of adrenodoxin binding
Author(s): Sagadin, Tanja
Riehm, Jan
Putkaradze, Natalia
Hutter, Michael C.
Bernhardt, Rita
Language: English
Title: FEBS Journal, The
Volume: 286
Issue: 6
Startpage: 1240
Endpage: 1249
Publisher/Platform: Wiley-Blackwell - STM
Year of Publication: 2019
Publikation type: Journal Article
Abstract: Bacterial P450s have considerable potential for biotechnological applications. The P450 CYP106A2 from Bacillus megaterium ATCC 13368 converts progesterone to several hydroxylated products that are important precursors for pharmaceutical substances. As high yields of monohydroxylated products are required for biotechnological processes, improving this conversion is of considerable interest. It has previously been shown that the binding mode of the redox partner can affect the selectivity of the progesterone hydroxylation, being more stringent in case of the Etp1 compared with Adx(4-108). Therefore, in this study we aimed to improve hydroxylation selectivity by optimizing the binding of Adx(4-108) with CYP106A2 allowing for a shorter distance between both redox centers. To change the putative binding interface of Adx(4-108) with CYP106A2, molecular docking was used to choose mutation sites for alteration. Mutants at positions Y82 and P108 of Adx were produced and investigated, and confirmed our hypothesis. Protein-protein docking, as well as conversion studies, using the mutants demonstrated that the iron-sulfur(FeS) cluster/heme distance diminished significantly, which subsequently led to an approximately 2.5-fold increase in 15β-hydroxyprogesterone, the main product of progesterone conversion by CYP106A2.
DOI of the first publication: 10.1111/febs.14722
URL of the first publication: https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.14722
Link to this record: hdl:20.500.11880/28024
http://dx.doi.org/10.22028/D291-29473
ISSN: 1432-1033
0014-2956
1742-4658
1742-464X
Date of registration: 8-Oct-2019
Faculty: NT - Naturwissenschaftlich- Technische Fakultät
Department: NT - Biowissenschaften
Collections:UniBib – Die Universitätsbibliographie

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