SYNTHESIS OF ANTIBIOTICS (CEPHALOGLYCIN) CATALYZED BY PENICILLIN-G ACYLASE - EVALUATION AND OPTIMIZATION OF DIFFERENT SYNTHETIC APPROACHES

Citation
R. Fernandezlafuente et al., SYNTHESIS OF ANTIBIOTICS (CEPHALOGLYCIN) CATALYZED BY PENICILLIN-G ACYLASE - EVALUATION AND OPTIMIZATION OF DIFFERENT SYNTHETIC APPROACHES, Enzyme and microbial technology, 19(1), 1996, pp. 9-14
Citations number
16
Categorie Soggetti
Biothechnology & Applied Migrobiology
ISSN journal
01410229
Volume
19
Issue
1
Year of publication
1996
Pages
9 - 14
Database
ISI
SICI code
0141-0229(1996)19:1<9:SOA(CB>2.0.ZU;2-V
Abstract
Two different approaches have been utilized to synthesize cephaloglyci n using immobilized-stabilized penicillin G acylase derivatives. These are thermodynamically and kinetically controlled strategies. The ther modynamically controlled strategy could be employed to synthesize ceph alotin or penicillin G, but this approach in the synthesis of cephalog lycin presented serious difficulties because of the absence of conditi ons where the thermodynamics of the process and the enzyme activity/st ability properties were good enough. The kinetically controlled strate gy has given much better results. The systematic study of the differen t parameters that defined the maximum yields for this strategy has per mitted the identification of its main problem as the hydrolysis of the antibiotic. Because of the rapid enzymatic hydrolysis of cephaloglyci n that has been previously synthetized, the yields were poor and they decreased very rapidly after reaching the maximum yield. Three differe nt strategies have been used to decrease this amidase activity (an exc ess of acyl donor, selection of acidic pH, and distortion of the enzym e molecule by methanol). Simultaneous utilization of these strategies has significantly improved this synthetic process with very high yield s (around 95%), reaction rates, and enzyme stability.