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Inhibitory effects in the side reactions occurring during the enzymic synthesis of amoxicillin: p ‐hydroxyphenylglycine methyl ester and amoxicillin hydrolysis
Author(s) -
Gonçalves Luciana R. B.,
FernandezLafuente Roberto,
Guisan Jose M.,
Giordano Raquel L. C.,
Giordano Roberto C.
Publication year - 2003
Publication title -
biotechnology and applied biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 70
eISSN - 1470-8744
pISSN - 0885-4513
DOI - 10.1042/ba20030016
Subject(s) - amoxicillin , chemistry , hydrolysis , methanol , kinetics , enzyme , antibiotics , chromatography , organic chemistry , biochemistry , physics , quantum mechanics
Penicillin G acylase immobilized on glyoxyl‐agarose is used to catalyse the reaction between p ‐hydroxyphenylglycine methyl ester (POHPGME) and 6‐aminopenicillanic acid (6‐APA). Inhibitory effects affecting the side reactions that occur during the synthesis of amoxicillin have been reported and need to be considered when proposing a kinetic model for the enzymic synthesis. In this work, we present a semi‐empirical kinetic model that successively includes different inhibitory effects in the rate equations. The model performance was always compared with experimental data on amoxicillin synthesis. Enzyme load and stirring rate were chosen to prevent diffusional effects. Our results indicate that POHPGME and amoxicillin were competitive inhibitors of the hydrolysis of amoxicillin and POHPGME, respectively. 6‐APA was a competitive inhibitor of the hydrolysis of amoxicillin. POHPG was a competitive inhibitor and methanol a non‐competitive inhibitor of the hydrolysis of both ester and antibiotic, but the action of methanol was only noticeable at very high concentrations. Adding inhibitory effects to the kinetic model led to a significant increase in the accuracy of the simulations of the overall process of synthesis.