Min Bora, Park Jeemin, Sim Yong-Kyun, Jung Suhyun, Kim Seong-Ho, Song Jae Kwang, Kim Bum Tae, Park Sang Youn, Yun Jaesook, Park Seongsoon, Lee Hyuk
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).
Chembiochem. 2015 Jan 2;16(1):77-82. doi: 10.1002/cbic.201402563. Epub 2014 Dec 4.
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.
