Journal article
Enzymatic reactive crystallization for improving ampicillin synthesis
Chemical engineering science, v 165, pp 81-88
29 Jun 2017
Abstract
The enzyme penicillin G acylase (PGA) catalyzes the condensation of phenylglycine methyl ester (PGME) with 6-aminopenicillanic acid (6-APA) to form ampicillin. We improved the selectivity of ampicillin synthesis with PGA by running simultaneous reaction and crystallization. However, the enzyme also catalyzes two undesirable side reactions: the hydrolysis of PGME to phenylglycine and the hydrolysis of ampicillin to phenylglycine and 6-APA. We demonstrate that a fifty percent improvement in selectivity for ampicillin over phenylglycine is achieved by combining reaction and crystallization in batch at pH value of 6 with saturated 6-APA and equimolar PGME. The enhancement in selectivity is mainly attributed to the decreased rates of enzymatic ampicillin hydrolysis; however, the course of the pH value during the reaction also has an effect on enzyme activity that improved selectivity. In addition to showing experimental results, we developed a new kinetic process model that predicts the observed improvement. The new model accounts for the solubility limits of different species as functions of pH value as well as the large change in pH value at high conversion. Previous work does not account for changes in activity with conversion. The pH-dependent activity for the specific enzyme used in this system, Assemblase (R) from DSM-Sinochem, is well-realized by the model and generalization to other PGAs is possible within the model framework; the selectivity parameters alpha, beta(0), and gamma for Assemblase (R) are compared to PGA from E. coli as evidence. (C) 2017 Elsevier Ltd. All rights reserved.
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Details
- Title
- Enzymatic reactive crystallization for improving ampicillin synthesis
- Creators
- Matthew A. McDonald - Georgia Institute of TechnologyAndreas S. Bommarius - Georgia Institute of TechnologyRonald W. Rousseau - Georgia Institute of Technology
- Publication Details
- Chemical engineering science, v 165, pp 81-88
- Publisher
- Elsevier
- Number of pages
- 8
- Grant note
- Georgia Research Alliance (Atlanta, GA, USA)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Chemical and Biological Engineering
- Web of Science ID
- WOS:000399489200009
- Scopus ID
- 2-s2.0-85014150166
- Other Identifier
- 991021958008704721
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Engineering, Chemical