Hydrogen‐Bonding‐Driven Enantioselective Resolution against the Kazlauskas Rule To Afford γ‐Amino Alcohols by Candida rugosa Lipase. Issue 1 (4th December 2014)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Chembiochem. Volume 16:Issue 1(2015)
• Page Start: 77
• Page End: 82
• Publication Date: 2014-12-04
• Subjects: Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.201402563
• Languages: English
• ISSNs: 1439-4227

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>Most lipases resolve secondary alcohols in accordance with the "Kazlauskas rule" to give the <italic>R</italic> enantiomers. In a similar manner to other lipases, <italic>Candida rugosa</italic> lipase (CRL) exhibits <italic>R</italic> enantioselectivity towards heptan‐2‐ol, although the enantiomeric ratio (<italic>E</italic>) is low (<italic>E</italic>=1.6). However, unexpected enantioselectivity (i.e., <italic>S</italic> enantioselectivity, <italic>E</italic>=58) of CRL towards 4‐(<italic>tert</italic>‐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 <italic>S</italic> enantiomer.</p> </abstract>