Asymmetric synthesis of (S)-ethyl-4-chloro-3-hydroxy butanoate using a Saccharomyces cerevisiae reductase: enantioselectivity and enzyme-substrate docking studies.
Biochim Biophys Acta
; 1804(9): 1841-9, 2010 Sep.
Article
in En
| MEDLINE
| ID: mdl-20601218
ABSTRACT
Ethyl (S)-4-chloro-3-hydroxy butanoate (ECHB) is a building block for the synthesis of hypercholesterolemia drugs. In this study, various microbial reductases have been cloned and expressed in Escherichia coli. Their reductase activities toward ethyl-4-chloro oxobutanoate (ECOB) have been assayed. Amidst them, Baker's yeast YDL124W, YOR120W, and YOL151W reductases showed high activities. YDL124W produced (S)-ECHB exclusively, whereas YOR120W and YOL151W made (R)-form alcohol. The homology models and docking models with ECOB and NADPH elucidated their substrate specificities and enantioselectivities. A glucose dehydrogenase-coupling reaction was used as NADPH recycling system to perform continuously the reduction reaction. Recombinant E. coli cell co-expressing YDL124W and Bacillus subtilis glucose dehydrogenase produced (S)-ECHB exclusively.
Full text:
1
Database:
MEDLINE
Main subject:
Oxidoreductases
/
Saccharomyces cerevisiae
/
Butyrates
/
Saccharomyces cerevisiae Proteins
Language:
En
Journal:
Biochim Biophys Acta
Year:
2010
Type:
Article