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Biotechnol Bioeng ; 78(4): 395-402, 2002 May 20.
Article in English | MEDLINE | ID: mdl-11948446

ABSTRACT

In the present downstream processing of penicillin G, penicillin G is extracted from the fermentation broth with an organic solvent and purified as a potassium salt via a number of back-extraction and crystallization steps. After purification, penicillin G is hydrolyzed to 6-aminopenicillanic acid, a precursor for many semisynthetic beta-lactam antibiotics. We are studying a reduction in the number of pH shifts involved and hence a large reduction in the waste salt production. To this end, the organic penicillin G extract is directly to be added to an aqueous immobilized enzyme suspension reactor and hydrolyzed by extractive catalysis. We found that this conversion can exceed 90% because crystallization of 6-aminopenicillanic acid shifts the equilibrium to the product side. A model was developed for predicting the equilibrium conversion in batch systems containing both a water and a butyl acetate phase, with either potassium or D-p-hydroxyphenylglycine methyl ester as counter-ion of penicillin G. The model incorporates the partitioning equilibrium of the reactants, the enzymatic reaction equilibrium, and the crystallization equilibrium of 6-aminopenicillanic acid. The model predicted the equilibrium conversion of Pen G quite reasonably for different values of pH, initial penicillin G concentration and phase volume ratio. The model can be used as a tool for optimizing the enzymatic hydrolysis.


Subject(s)
Acetates/metabolism , Glycine/analogs & derivatives , Models, Chemical , Penicillanic Acid/isolation & purification , Penicillanic Acid/metabolism , Penicillin G/metabolism , Catalysis , Chromatography, High Pressure Liquid/methods , Computer Simulation , Crystallization , Escherichia coli/enzymology , Fermentation , Glycine/chemistry , Hydrogen-Ion Concentration , Hydrolysis , Penicillanic Acid/analogs & derivatives , Penicillanic Acid/chemistry , Penicillin Amidase/metabolism , Penicillin G/isolation & purification , Potassium/chemistry , Reproducibility of Results , Sensitivity and Specificity , Water/chemistry
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