Microbial asymmetric hydrolysis of 3-substituted glutaric acid diamides
Article first published online: 13 AUG 2013
© 2013 The Society for Applied Microbiology
Journal of Applied Microbiology
Volume 115, Issue 5, pages 1127–1133, November 2013
How to Cite
Nojiri, M., Uekita, K., Ohnuki, M., Taoka, N. and Yasohara, Y. (2013), Microbial asymmetric hydrolysis of 3-substituted glutaric acid diamides. Journal of Applied Microbiology, 115: 1127–1133. doi: 10.1111/jam.12309
- Issue published online: 15 OCT 2013
- Article first published online: 13 AUG 2013
- Accepted manuscript online: 23 JUL 2013 05:35AM EST
- Manuscript Accepted: 17 JUL 2013
- Manuscript Revised: 3 JUL 2013
- Manuscript Received: 22 MAY 2013
- Comamonas sp;
- glutaric acid diamide derivatives;
Micro-organisms were screened for their ability to produce (R)-3-(4-chlorophenyl) glutaric acid monoamide (CGM) from 3-(4-chlorophenyl) glutaric acid diamide (CGD) through stereoselective hydrolysis. (R)-CGM is a useful synthetic intermediate for arbaclofen.
Methods and Results
Four CGD-assimilating micro-organisms were found to be potential catalysts for (R)-CGM production. Among these micro-organisms, Comamonas sp. KNK3-7 (NITE BP-963) produced (R)-CGM with the highest optical purity [98·7% enantiomeric excess (e.e.)] and was selected as the most promising strain. In addition, Comamonas sp. KNK3-7 could asymmetrically hydrolyse 3-isobutyl glutaric acid diamide (IBD) to produce (R)-3-isobutyl glutaric acid monoamide [(R)-IBM] with high optical purity (>99·0% e.e.).
The synthesis of a (R)-3-substituted glutaric acid monoamide by desymmetrization of 3-substituted glutaric acid diamide with a micro-organism and an enzyme has not been previously reported. This finding indicates the possibility of the preparation of a variety of optically active 3-substituted glutaric acid monoamides using the amidase from Comamonas sp. KNK3-7.
Significance and Impact of the Study
The amidase from Comamonas sp. KNK3-7 may be useful for the chemoenzymatic synthesis of various kinds of chiral gamma-aminobutyric acids and may be used in a ‘green’ process to produce gamma-aminobutyric acids.