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
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.