title: Hydrogen-bonding-driven enantioselective resolution against the Kazlauskas rule to afford γ-amino alcohols by Candida rugosa lipase.
abstract: Most lipases resolve secondary alcohols in accordance with the "Kazlauskas rule" to give the R enantiomers. In a similar manner to other lipases, Candida rugosa lipase (CRL) exhibits R enantioselectivity towards heptan-2-ol, although the enantiomeric ratio (E) is low (E=1.6). However, unexpected enantioselectivity (i.e., S enantioselectivity, E=58) of CRL towards 4-(tert-butoxycarbonylamino)butan-2-ol, which has a similar chain length to heptan-2-ol, has been observed. To develop a deeper understanding of the molecular basis for this unusual enantioselectivity, we have conducted a series of molecular modeling and substrate engineering experiments. The results of these computational and experimental analyses indicated that a hydrogen bond between the Ser450 residue and the nitrogen atom of the carbamate group is critical to stabilize the transition state of the S enantiomer.
authors.affiliation: Medicinal Chemistry Research Center, Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong-gu, Daejeon 305-600 (South Korea); Department of Chemistry and Institute of Basic Science, Sungkyunkwan University, 2066 Seobu-Ro, Jangan-Gu, Suwon 440-746 (South Korea).
authors.forename: Bora
authors.initials: B
authors.lastname: Min
authors.forename: Jeemin
authors.initials: J
authors.lastname: Park
authors.forename: Yong-Kyun
authors.initials: YK
authors.lastname: Sim
authors.forename: Suhyun
authors.initials: S
authors.lastname: Jung
authors.forename: Seong-Ho
authors.initials: SH
authors.lastname: Kim
authors.forename: Jae Kwang
authors.initials: JK
authors.lastname: Song
authors.forename: Bum Tae
authors.initials: BT
authors.lastname: Kim
authors.forename: Sang Youn
authors.initials: SY
authors.lastname: Park
authors.forename: Jaesook
authors.initials: J
authors.lastname: Yun
authors.forename: Seongsoon
authors.initials: S
authors.lastname: Park
authors.forename: Hyuk
authors.initials: H
authors.lastname: Lee
mesh_terms: D000605:Amino Alcohols / Q000737:chemistry*; D002175:Candida / Q000737:chemistry* / Q000201:enzymology; D005656:Fungal Proteins / Q000737:chemistry*; D019850:Heptanol / Q000737:chemistry*; D006860:Hydrogen Bonding; D007700:Kinetics; D008049:Lipase / Q000737:chemistry*; D008958:Models, Molecular; D011994:Recombinant Proteins / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D000605:Amino Alcohols; D005656:Fungal Proteins; D011994:Recombinant Proteins; D019850:Heptanol; D008049:Lipase
keywords: Kazlauskas rule; amino alcohols; kinetic resolution; lipases; molecular modeling