Regio‐ and Stereoselective Steroid Hydroxylation at C7 by Cytochrome P450 Monooxygenase Mutants
Abstract: Steroidal C7β alcohols and their respective esters have shown significant promise as neuroprotective and anti‐inflammatory agents to treat chronic neuronal damage like stroke, brain trauma, and cerebral ischemia. Since C7 is spatially far away from any functional groups that could direct C−H activation, these transformations are not readily accessible using modern synthetic organic techniques. Reported here are P450‐BM3 mutants that catalyze the oxidative hydroxylation of six different steroids with pronounced C7 regioselectivities and β stereoselectivities, as well as high activities. These challenging transformations were achieved by a focused mutagenesis strategy and application of a novel technology for protein library construction based on DNA assembly and USER (Uracil‐Specific Excision Reagent) cloning. Upscaling reactions enabled the purification of the respective steroidal alcohols in moderate to excellent yields. The high‐resolution X‐ray structure and molecular dynamics simulations of the best mutant unveil the origin of regio‐ and stereoselectivity.
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Erschienen in
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Regio‐ and Stereoselective Steroid Hydroxylation at C7 by Cytochrome P450 Monooxygenase Mutants ; volume:132 ; number:30 ; year:2020 ; pages:12599-12605 ; extent:7
Angewandte Chemie ; 132, Heft 30 (2020), 12599-12605 (gesamt 7)
- Urheber
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Li, Aitao
Acevedo‐Rocha, Carlos G.
D'Amore, Lorenzo
Chen, Jinfeng
Peng, Yaqin
Garcia‐Borràs, Marc
Gao, Chenghua
Zhu, Jinmei
Rickerby, Harry
Osuna, Sílvia
Zhou, Jiahai
Reetz, Manfred T.
- DOI
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10.1002/ange.202003139
- URN
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urn:nbn:de:101:1-2022053007010470970588
- Rechteinformation
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
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15.08.2025, 07:30 MESZ
Datenpartner
Deutsche Nationalbibliothek. Bei Fragen zum Objekt wenden Sie sich bitte an den Datenpartner.
Beteiligte
- Li, Aitao
- Acevedo‐Rocha, Carlos G.
- D'Amore, Lorenzo
- Chen, Jinfeng
- Peng, Yaqin
- Garcia‐Borràs, Marc
- Gao, Chenghua
- Zhu, Jinmei
- Rickerby, Harry
- Osuna, Sílvia
- Zhou, Jiahai
- Reetz, Manfred T.
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