title: Regioselective C-H hydroxylation of omeprazole sulfide by Bacillus megaterium CYP102A1 to produce a human metabolite.
abstract: OBJECTIVE
  To find a simple enzymatic strategy for the efficient synthesis of the expensive 5'-hydroxyomeprazole sulfide, a recently identified minor human metabolite, from omeprazole sulfide, which is an inexpensive substrate.
  
  
  RESULTS
  The practical synthetic strategy for the 5'-OH omeprazole sulfide was accomplished with a set of highly active CYP102A1 mutants, which were obtained by blue colony screening from CYP102A1 libraries with a high conversion yield. The mutant and even the wild-type enzyme of CYP102A1 catalyzed the high regioselective (98 %) C-H hydroxylation of omeprazole sulfide to 5'-OH omeprazole sulfide with a high conversion yield (85-90 %).
  
  
  CONCLUSIONS
  A highly efficient synthesis of 5'-OH omeprazole sulfide was developed using CYP102A1 from Bacillus megaterium as a biocatalyst.
authors.affiliation: School of Biological Sciences and Technology, Chonnam National University, 77 Yongbongro, Gwangju, 61186, Republic of Korea.
authors.forename: Hyun-Hee
authors.initials: HH
authors.lastname: Jang
authors.affiliation: School of Biological Sciences and Technology, Chonnam National University, 77 Yongbongro, Gwangju, 61186, Republic of Korea.
authors.forename: Sang-Hoon
authors.initials: SH
authors.lastname: Ryu
authors.affiliation: School of Biological Sciences and Technology, Chonnam National University, 77 Yongbongro, Gwangju, 61186, Republic of Korea.
authors.forename: Thien-Kim
authors.initials: TK
authors.lastname: Le
authors.affiliation: School of Biological Sciences and Technology, Chonnam National University, 77 Yongbongro, Gwangju, 61186, Republic of Korea.
authors.forename: Tiep Thi My
authors.initials: TT
authors.lastname: Doan
authors.affiliation: School of Biological Sciences and Technology, Chonnam National University, 77 Yongbongro, Gwangju, 61186, Republic of Korea.
authors.forename: Thi Huong Ha
authors.initials: TH
authors.lastname: Nguyen
authors.affiliation: Gwangju Center, Korea Basic Science Institute, Gwangju, 61186, Republic of Korea.
authors.forename: Ki Deok
authors.initials: KD
authors.lastname: Park
authors.affiliation: Department of Pharmacology and Pharmacogenomics Center, Inje University College of Medicine, Busan, 47392, Republic of Korea.
authors.forename: Da-Eun
authors.initials: DE
authors.lastname: Yim
authors.affiliation: Department of Pharmacology and Pharmacogenomics Center, Inje University College of Medicine, Busan, 47392, Republic of Korea.
authors.forename: Dong-Hyun
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Hoseo University, Asan-si, Chungcheongnam-do, 31499, Republic of Korea.
authors.forename: Choong-Kyung
authors.initials: CK
authors.lastname: Kang
authors.affiliation: College of Veterinary Medicine, Chonnam National University, Gwangju, 61186, Republic of Korea.
authors.forename: Taeho
authors.initials: T
authors.lastname: Ahn
authors.affiliation: School of Biological Sciences and Technology, Chonnam National University, 77 Yongbongro, Gwangju, 61186, Republic of Korea.
authors.forename: Hyung-Sik
authors.initials: HS
authors.lastname: Kang
authors.affiliation: School of Biological Sciences and Technology, Chonnam National University, 77 Yongbongro, Gwangju, 61186, Republic of Korea. chyun@jnu.ac.kr.
authors.forename: Chul-Ho
authors.initials: CH
authors.lastname: Yun
mesh_terms: D001410:Bacillus megaterium / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism; D002384:Catalysis; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006801:Humans; D006900:Hydroxylation; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D009853:Omeprazole / Q000031:analogs & derivatives* / Q000378:metabolism; D013237:Stereoisomerism
chemical_list: D001426:Bacterial Proteins; C040449:omeprazole sulfide; D003577:Cytochrome P-450 Enzyme System; D009251:NADPH-Ferrihemoprotein Reductase; C052423:flavocytochrome P450 BM3 monoxygenases; D009853:Omeprazole
keywords: 5-Hydroxyomeprazole sulphide; CYP102A1 mutant; Human metabolite; Hydroxylation; Omeprazole sulfide; Regioselectivity