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Indian Journal of Biotechnology (IJBT) >
IJBT Vol.11 [2012] >
IJBT Vol.11(1) [January 2012] >
| Title: | Enzymatic synthesis of ß-lactams: Constraints and control |
| Authors: | Samanta, Timir B |
| Keywords: | Immobilized Penicillin Acylase
ß-lactams
Solvents
Synthesis
Water Activity |
| Issue Date: | Jan-2012 |
| Publisher: | NISCAIR-CSIR, India |
| Abstract: | The constraint in synthesis of ß-lactams by
penicillin acylase is the hydrolysis of the activated acyl donor and the
synthetic product. The thermodynamically controlled synthesis of ß-lactams
deals with direct acylation of a nucleophile (6-APA, 7-ACA or 7-ADCA) by free
acids in acidic pH and high
concentration of solvent to achieve good yield. On the other hand, the
kinetically controlled synthesis with esters is much faster. However, success
and yield of kinetically controlled synthesis depend on combined application of
an insolubilized catalyst, optimum pH
of the reaction, addition of suitable solvent and high concentration of
actvated acyl donor and ß-lactam nucleus. Water miscible solvents play an
important role in the synthesis. The choice of solvent is guided by its
inhibitory effect on enzyme activity and deleterious effect on enzyme
stability. Synthetic yield of cefazolin in presence of water-miscible solvent
is reduced, while the reaction carried in water-immiscible solvent markedly
improves the yield of cefazolin, possibly due to reduction in hydrolysis of
acyl donor and the product. Ethylene glycol inhibits more the hydrolysis of
ampicillin than the hydrolysis of PGME and the synthetase/amidase ratio varies
depending on the concentration of the solvent used. Hydrolytic vs synthetic activity of penicillin
acylase is also influenced by water activity of the insolubilized catalyst.
Shuffling of PA-encoding genes has been shown to improve the ß-lactam
synthesis. Delineation of enzyme-solvent interaction needs close scrutiny to
ensure further success in biocatalysis and synthesis of ß-lactams in
particular. |
| Page(s): | 7-15 |
| CC License: |  CC Attribution-Noncommercial-No Derivative Works 2.5 India |
| ISSN: | 0975-0967 (Online); 0972-5849 (Print) |
| Source: | IJBT Vol.11(1) [January 2012]
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