Chiral-substrate-assisted stereoselective epoxidation catalyzed by H 2O 2-dependent cytochrome P450 SPα

Takashi Fujishiro, Osami Shoji, Norifumi Kawakami, Takahiro Watanabe, Hiroshi Sugimoto, Yoshitsugu Shiro, Yoshihito Watanabe

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

The stereoselective epoxidation of styrene was catalyzed by H 2O 2-dependent cytochrome P450 SPα in the presence of carboxylic acids as decoy molecules. The stereoselectivity of styrene oxide could be altered by the nature of the decoy molecules. In particular, the chirality at the α-positions of the decoy molecules induced a clear difference in the chirality of the product: (R)-ibuprofen enhanced the formation of (S)-styrene oxide, whereas (S)-ibuprofen preferentially afforded (R)-styrene oxide. The crystal structure of an (R)-ibuprofen-bound cytochrome P450 SPα (resolution 1.9 Å) revealed that the carboxylate group of (R)-ibuprofen served as an acid-base catalyst to initiate the epoxidation. A docking simulation of the binding of styrene in the active site of the (R)-ibuprofen-bound form suggested that the orientation of the vinyl group of styrene in the active site agreed with the formation of (S)-styrene oxide. The stereoselective epoxidation of styrene was catalyzed by H 2O 2-dependent cytochrome P450 SPα in the presence of carboxylic acids as decoy molecules. The stereoselectivity of the reaction could be altered by the nature of the decoy molecules, such as ibuprofen.

Original languageEnglish
Pages (from-to)2286-2293
Number of pages8
JournalChemistry - An Asian Journal
Volume7
Issue number10
DOIs
Publication statusPublished - 2012 Oct
Externally publishedYes

Fingerprint

styrene oxide
Epoxidation
Ibuprofen
Cytochrome P-450 Enzyme System
Styrene
Substrates
Molecules
Stereoselectivity
Chirality
Carboxylic Acids
Catalytic Domain
Crystal structure
Catalysts
Acids

Keywords

  • carboxylic acids
  • chirality
  • decoy molecules
  • epoxidation
  • hydrogen peroxide

ASJC Scopus subject areas

  • Chemistry(all)
  • Medicine(all)

Cite this

Chiral-substrate-assisted stereoselective epoxidation catalyzed by H 2O 2-dependent cytochrome P450 SPα . / Fujishiro, Takashi; Shoji, Osami; Kawakami, Norifumi; Watanabe, Takahiro; Sugimoto, Hiroshi; Shiro, Yoshitsugu; Watanabe, Yoshihito.

In: Chemistry - An Asian Journal, Vol. 7, No. 10, 10.2012, p. 2286-2293.

Research output: Contribution to journalArticle

Fujishiro, Takashi ; Shoji, Osami ; Kawakami, Norifumi ; Watanabe, Takahiro ; Sugimoto, Hiroshi ; Shiro, Yoshitsugu ; Watanabe, Yoshihito. / Chiral-substrate-assisted stereoselective epoxidation catalyzed by H 2O 2-dependent cytochrome P450 SPα In: Chemistry - An Asian Journal. 2012 ; Vol. 7, No. 10. pp. 2286-2293.
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