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Kinetic resolution of chiral amines with ω‐transaminase using an enzyme‐membrane reactor
Author(s) -
Shin JongShik,
Kim ByungGee,
Liese Andreas,
Wandrey Christian
Publication year - 2001
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.1050
Subject(s) - hollow fiber membrane , chemistry , membrane reactor , chromatography , enantiomeric excess , substrate (aquarium) , acetophenone , kinetic resolution , membrane , nuclear chemistry , organic chemistry , biochemistry , enantioselective synthesis , catalysis , oceanography , geology
A kinetic resolution process for the production of chiral amines was developed using an enzyme‐membrane reactor (EMR) and a hollow‐fiber membrane contactor with (S)‐specific ω‐transaminases (ω‐TA) from Vibrio fluvialis JS17 and Bacillus thuringiensis JS64. The substrate solution containing racemic amine and pyruvate was recirculated through the EMR and inhibitory ketone product was selectively extracted by the membrane contactor until enantiomeric excess of (R)‐amine exceeded 95%. Using the reactor set‐up with flat membrane reactor (10‐mL working volume), kinetic resolutions of α‐methylbenzylamine (α‐MBA) and 1‐aminotetralin (200 m M, 50 mL) were carried out. During the operation, concentration of ketone product, i.e., acetophenone or α‐tetralone, in a substrate reservoir was maintained below 0.1 m M, suggesting efficient removal of the inhibitory ketone by the membrane contactor. After 47 and 32.5 h of operation using 5 U/mL of enzyme, 98.0 and 95.5% ee of (R)‐α‐MBA and (R)‐1‐aminotetralin were obtained at 49.5 and 48.8% of conversion, respectively. A hollow‐fiber membrane reactor (39‐mL working volume) was used for a preparative‐scale kinetic resolution of 1‐aminotetralin (200 m M, 1 L). After 133 h of operation, enantiomeric excess reached 95.6% and 14.3 g of (R)‐1‐aminotetralin was recovered (97.4% of yield). Mathematical modeling of the EMR process including the membrane contactor was performed to evaluate the effect of residence time. The simulation results suggest that residence time should be short to maintain the concentration of the ketone product in EMR sufficiently low so as to decrease conversion per cycle and, in turn, reduce the inhibition of the ω‐TA activity. © 2001 John Wiley & Sons, Inc. Biotechnol Bioeng 73: 179–187, 2001.