Journal
PROCESS BIOCHEMISTRY
Volume 44, Issue 11, Pages 1270-1275Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.procbio.2009.07.011
Keywords
Asymmetric reduction; Biosynthesis; Candida krusei; Ethyl 2-oxo-4-phenylbutyrate (OPBE); Ethyl (R)-2-hydroxy-4-phenylbutyrate ((R)-HPBE)
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Funding
- National Natural Science Foundation of China [20476039]
- State Key Basic Research and Development Plan of China [2003CB716008]
- National High Technology Research and Development Program of China [2007AA02Z226]
- Program for Changjiang Scholars and Innovative Research Team in University [IRT0532]
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Ethyl (R)-2-hydroxy-4-phenylbutyrate ((R)-HPBE), a key intermediate in the production of angiotensin-converting enzyme (ACE) inhibitors, was prepared by the microbial reduction of ethyl 2-oxo-4-phenylbutyrate (OPBE). Among 63 microorganisms tested, Candida krusei SW2026, for the first time, was proven to be a highly effective biocatalyst in this reduction process, leading to the (R)-enantiomer in 99.7% ee and 95.1% yield at 2.5 g/L of OPBE (under optimal conditions of 30 degrees C, pH 6.6, and in the presence of 5% glucose as co-substrate). In order to achieve higher product concentration with desired enantiopurity and yield for application in large-scale production, strategies such as substrate fed-batch and aqueous/organic biphasic system were successfully conducted in the biotransformation reaction. At 20 g/L of OPBE, the enantiomeric excess (ee), yield, and product concentration were enhanced to 97.4%, 82.0%, and 16.6 g/L, respectively, in water/dibutyl phthalate biphasic system, compared with 87.5%, 45.8%, and 9.2 g/L in aqueous medium. This study provides an attractive process of (R)-HPBE production for potential green chemistry applications. (C) 2009 Elsevier Ltd. All rights reserved.
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