Please use this identifier to cite or link to this item: https://hdl.handle.net/11147/12507
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dc.contributor.authorKestevur Doğru, Ekinen_US
dc.contributor.authorGüralp, Gülceen_US
dc.contributor.authorUyar, Arzuen_US
dc.contributor.authorSürmeli, Nur Başaken_US
dc.date.accessioned2022-10-03T11:38:58Z-
dc.date.available2022-10-03T11:38:58Z-
dc.date.issued2023-01-
dc.identifier.urihttps://doi.org/10.1016/j.jmgm.2022.108323-
dc.identifier.urihttps://hdl.handle.net/11147/12507-
dc.description.abstractSteroid-based chemicals can affect the metabolism, immune functions, and development of sexual characteristics. Because of these effects, steroid derivatives are widely used in the pharmaceutical industry. Progesterone is a steroid-based hormone that mainly controls the ovulation period of women but is also a precursor molecule for the synthesis of important hormones like testosterone and cortisone. Cytochrome P450 (CYP) enzymes are important for the production of hydroxyprogesterones in the industry since they can catalyze regio- and enantioselective hydroxylation reactions. Although human CYP enzymes can catalyze hydroxyprogesterone synthesis with high selectivity, these enzymes are membrane bound, which limits their application for industrial production. CYP119 is a soluble and thermophilic enzyme from the archaea Sulfolobus acidocaldarius. Even though the native substrate of the enzyme is not known, CYP119 can catalyze styrene epoxidation, lauric acid hydroxylation, and Amplex®Red peroxidation. In this work, an in silico mutagenesis approach was used to design CYP119 mutants with high progesterone affinity. Energy scores of progesterone docking simulations were used for the design and elimination of single, double, and triple mutants of CYP119. Among designed 674 mutants, five of them match the criteria for progesterone hydroxylation. The most common mutation of these five mutants, L69G mutant was analyzed using independent molecular dynamics (MD) simulations in comparison with the wild-type (WT) enzyme. L69G CYP119, was expressed and isolated from Escherichia coli; it showed 800-fold higher affinity for progesterone compared to WT CYP119. L69G CYP119 also catalyzed progesterone hydroxylation. The novel designed enzyme L69G CYP119 is a potential versatile biocatalyst for progesterone hydroxylation that is expected to be stable under industrial production conditions.en_US
dc.language.isoenen_US
dc.publisherElsevieren_US
dc.relationBir Sitokrom P450 Enziminin Progesteron Hidroksilasyonu İçin Rasyonel Tasarımıen_US
dc.relation.ispartofJournal of Molecular Graphics and Modellingen_US
dc.rightsinfo:eu-repo/semantics/embargoedAccessen_US
dc.subjectCYP119en_US
dc.subjectMolecular dynamicsen_US
dc.subjectProgesteroneen_US
dc.subjectProtein designen_US
dc.titleRational design of thermophilic CYP119 for progesterone hydroxylation by in silico mutagenesis and docking screeningen_US
dc.typeArticleen_US
dc.authorid0000-0001-6153-4012en_US
dc.authorid0000-0002-1841-4004en_US
dc.institutionauthorKestevur Doğru, Ekinen_US
dc.institutionauthorGüralp, Gülceen_US
dc.institutionauthorUyar, Arzuen_US
dc.institutionauthorSürmeli, Nur Başaken_US
dc.departmentİzmir Institute of Technology. Bioengineeringen_US
dc.identifier.wosWOS:000882849100001en_US
dc.identifier.scopus2-s2.0-85138165612en_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.identifier.doi10.1016/j.jmgm.2022.108323-
dc.relation.issn1093-3263en_US
dc.description.volume118en_US
dc.relation.grantno2020IYTE0107en_US
dc.identifier.scopusqualityQ2-
item.languageiso639-1en-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.grantfulltextembargo_20250101-
item.cerifentitytypePublications-
item.fulltextWith Fulltext-
item.openairetypeArticle-
crisitem.author.dept01. Izmir Institute of Technology-
crisitem.author.dept03.01. Department of Bioengineering-
crisitem.author.dept03.01. Department of Bioengineering-
Appears in Collections:Bioengineering / Biyomühendislik
Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection
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