Asymmetric synthesis of (S)-ethyl-4-chloro-3-hydroxy butanoate using a Saccharomyces cerevisiae reductase: Enantioselectivity and enzyme-substrate docking studies

Jihye Jung; Hyun Joo Park; Ki Nam Uhm; Dooil Kim; Hyung Kwoun Kim

doi:10.1016/j.bbapap.2010.06.011

Asymmetric synthesis of (S)-ethyl-4-chloro-3-hydroxy butanoate using a Saccharomyces cerevisiae reductase: Enantioselectivity and enzyme-substrate docking studies

Jihye Jung, Hyun Joo Park, Ki Nam Uhm, Dooil Kim, Hyung Kwoun Kim

Biotechnology

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

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.

Original language	English
Pages (from-to)	1841-1849
Number of pages	9
Journal	Biochimica et Biophysica Acta - Proteins and Proteomics
Volume	1804
Issue number	9
DOIs	https://doi.org/10.1016/j.bbapap.2010.06.011
State	Published - Sep 2010

Bibliographical note

Funding Information:
This work was supported by the 21C Frontier Microbial Genomics and Applications Center Program, Ministry of Education, Science & Technology, Republic of Korea , and Gyeonggi Regional Research Center (GRRC) at the Catholic University of Korea .

Keywords

Chiral intermediate
Docking model
Enantioselectivity
Hyperlipidemia drug
Reductase

Access to Document

10.1016/j.bbapap.2010.06.011

Cite this

@article{e6c7008a06f44abd81e556e48fcf067c,

title = "Asymmetric synthesis of (S)-ethyl-4-chloro-3-hydroxy butanoate using a Saccharomyces cerevisiae reductase: Enantioselectivity and enzyme-substrate docking studies",

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.",

keywords = "Chiral intermediate, Docking model, Enantioselectivity, Hyperlipidemia drug, Reductase",

author = "Jihye Jung and Park, {Hyun Joo} and Uhm, {Ki Nam} and Dooil Kim and Kim, {Hyung Kwoun}",

note = "Funding Information: This work was supported by the 21C Frontier Microbial Genomics and Applications Center Program, Ministry of Education, Science & Technology, Republic of Korea , and Gyeonggi Regional Research Center (GRRC) at the Catholic University of Korea . ",

year = "2010",

month = sep,

doi = "10.1016/j.bbapap.2010.06.011",

language = "English",

volume = "1804",

pages = "1841--1849",

journal = "Biochimica et Biophysica Acta - Proteins and Proteomics",

issn = "1570-9639",

publisher = "Elsevier B.V.",

number = "9",

}

Asymmetric synthesis of (S)-ethyl-4-chloro-3-hydroxy butanoate using a Saccharomyces cerevisiae reductase: Enantioselectivity and enzyme-substrate docking studies. / Jung, Jihye; Park, Hyun Joo; Uhm, Ki Nam et al.
In: Biochimica et Biophysica Acta - Proteins and Proteomics, Vol. 1804, No. 9, 09.2010, p. 1841-1849.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Asymmetric synthesis of (S)-ethyl-4-chloro-3-hydroxy butanoate using a Saccharomyces cerevisiae reductase

T2 - Enantioselectivity and enzyme-substrate docking studies

AU - Jung, Jihye

AU - Park, Hyun Joo

AU - Uhm, Ki Nam

AU - Kim, Dooil

AU - Kim, Hyung Kwoun

N1 - Funding Information: This work was supported by the 21C Frontier Microbial Genomics and Applications Center Program, Ministry of Education, Science & Technology, Republic of Korea , and Gyeonggi Regional Research Center (GRRC) at the Catholic University of Korea .

PY - 2010/9

Y1 - 2010/9

N2 - 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.

AB - 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.

KW - Chiral intermediate

KW - Docking model

KW - Enantioselectivity

KW - Hyperlipidemia drug

KW - Reductase

UR - http://www.scopus.com/inward/record.url?scp=77955093031&partnerID=8YFLogxK

U2 - 10.1016/j.bbapap.2010.06.011

DO - 10.1016/j.bbapap.2010.06.011

M3 - Article

C2 - 20601218

AN - SCOPUS:77955093031

SN - 1570-9639

VL - 1804

SP - 1841

EP - 1849

JO - Biochimica et Biophysica Acta - Proteins and Proteomics

JF - Biochimica et Biophysica Acta - Proteins and Proteomics

IS - 9

ER -

Asymmetric synthesis of (S)-ethyl-4-chloro-3-hydroxy butanoate using a Saccharomyces cerevisiae reductase: Enantioselectivity and enzyme-substrate docking studies

Abstract

Bibliographical note

Keywords

Access to Document

Other files and links

Fingerprint

Cite this