Wen Zhang, Y. Ni, Zhi-hao Sun
Nov 1, 2009
Citations
1
Influential Citations
41
Citations
Journal
Process Biochemistry
Abstract
Abstract 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 °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.