Degradation Kinetics of Clavulanic Acid in Fermentation Broths at Low Temperatures
Clavulanic acid (CA) is a β-lactam antibiotic inhibitor of β-lactamase enzymes, which confers resistance to bacteria against several antibiotics. CA is produced in submerged cultures by the filamentous Gram-positive bacterium Streptomyces clavuligerus; yield and downstream process...
Main Authors: | , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2019-01-01
|
Series: | Antibiotics |
Subjects: | |
Online Access: | http://www.mdpi.com/2079-6382/8/1/6 |
id |
doaj-d81a1c45e8604cd88a6500c66859d20a |
---|---|
record_format |
Article |
spelling |
doaj-d81a1c45e8604cd88a6500c66859d20a2020-11-24T22:18:47ZengMDPI AGAntibiotics2079-63822019-01-0181610.3390/antibiotics8010006antibiotics8010006Degradation Kinetics of Clavulanic Acid in Fermentation Broths at Low TemperaturesDavid Gómez-Ríos0Howard Ramírez-Malule1Peter Neubauer2Stefan Junne3Rigoberto Ríos-Estepa4Grupo de Bioprocesos, Departamento de Ingeniería Química, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellín 050010, ColombiaEscuela de Ingeniería Química, Universidad del Valle, A.A. 25360, Cali 76001, ColombiaChair of Bioprocess Engineering, Institute of Biotechnology, Technische Universität Berlin, Ackerstr. 76, ACK 24, 13355 Berlin, GermanyChair of Bioprocess Engineering, Institute of Biotechnology, Technische Universität Berlin, Ackerstr. 76, ACK 24, 13355 Berlin, GermanyGrupo de Bioprocesos, Departamento de Ingeniería Química, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellín 050010, ColombiaClavulanic acid (CA) is a β-lactam antibiotic inhibitor of β-lactamase enzymes, which confers resistance to bacteria against several antibiotics. CA is produced in submerged cultures by the filamentous Gram-positive bacterium Streptomyces clavuligerus; yield and downstream process are compromised by a degradation phenomenon, which is not yet completely elucidated. In this contribution, a study of degradation kinetics of CA at low temperatures (−80, −20, 4, and 25 °C) and pH 6.8 in chemically-defined fermentation broths is presented. Samples of CA in the fermentation broths showed a fast decline of concentration during the first 5 h followed by a slower, but stable, reaction rate in the subsequent hours. A reversible-irreversible kinetic model was applied to explain the degradation rate of CA, its dependence on temperature and concentration. Kinetic parameters for the equilibrium and irreversible reactions were calculated and the proposed kinetic model was validated with experimental data of CA degradation ranging 16.3 mg/L to 127.0 mg/L. Degradation of the chromophore CA-imidazole, which is commonly used for quantifications by High Performance Liquid Chromatography, was also studied at 4 °C and 25 °C, showing a rapid rate of degradation according to irreversible first-order kinetics. A hydrolysis reaction mechanism is proposed as the cause of CA-imidazole loss in aqueous solutions.http://www.mdpi.com/2079-6382/8/1/6clavulanic aciddegradationkineticsequilibriumirreversibleimidazolereaction mechanismfermentation brothlow temperature |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
David Gómez-Ríos Howard Ramírez-Malule Peter Neubauer Stefan Junne Rigoberto Ríos-Estepa |
spellingShingle |
David Gómez-Ríos Howard Ramírez-Malule Peter Neubauer Stefan Junne Rigoberto Ríos-Estepa Degradation Kinetics of Clavulanic Acid in Fermentation Broths at Low Temperatures Antibiotics clavulanic acid degradation kinetics equilibrium irreversible imidazole reaction mechanism fermentation broth low temperature |
author_facet |
David Gómez-Ríos Howard Ramírez-Malule Peter Neubauer Stefan Junne Rigoberto Ríos-Estepa |
author_sort |
David Gómez-Ríos |
title |
Degradation Kinetics of Clavulanic Acid in Fermentation Broths at Low Temperatures |
title_short |
Degradation Kinetics of Clavulanic Acid in Fermentation Broths at Low Temperatures |
title_full |
Degradation Kinetics of Clavulanic Acid in Fermentation Broths at Low Temperatures |
title_fullStr |
Degradation Kinetics of Clavulanic Acid in Fermentation Broths at Low Temperatures |
title_full_unstemmed |
Degradation Kinetics of Clavulanic Acid in Fermentation Broths at Low Temperatures |
title_sort |
degradation kinetics of clavulanic acid in fermentation broths at low temperatures |
publisher |
MDPI AG |
series |
Antibiotics |
issn |
2079-6382 |
publishDate |
2019-01-01 |
description |
Clavulanic acid (CA) is a β-lactam antibiotic inhibitor of β-lactamase enzymes, which confers resistance to bacteria against several antibiotics. CA is produced in submerged cultures by the filamentous Gram-positive bacterium Streptomyces clavuligerus; yield and downstream process are compromised by a degradation phenomenon, which is not yet completely elucidated. In this contribution, a study of degradation kinetics of CA at low temperatures (−80, −20, 4, and 25 °C) and pH 6.8 in chemically-defined fermentation broths is presented. Samples of CA in the fermentation broths showed a fast decline of concentration during the first 5 h followed by a slower, but stable, reaction rate in the subsequent hours. A reversible-irreversible kinetic model was applied to explain the degradation rate of CA, its dependence on temperature and concentration. Kinetic parameters for the equilibrium and irreversible reactions were calculated and the proposed kinetic model was validated with experimental data of CA degradation ranging 16.3 mg/L to 127.0 mg/L. Degradation of the chromophore CA-imidazole, which is commonly used for quantifications by High Performance Liquid Chromatography, was also studied at 4 °C and 25 °C, showing a rapid rate of degradation according to irreversible first-order kinetics. A hydrolysis reaction mechanism is proposed as the cause of CA-imidazole loss in aqueous solutions. |
topic |
clavulanic acid degradation kinetics equilibrium irreversible imidazole reaction mechanism fermentation broth low temperature |
url |
http://www.mdpi.com/2079-6382/8/1/6 |
work_keys_str_mv |
AT davidgomezrios degradationkineticsofclavulanicacidinfermentationbrothsatlowtemperatures AT howardramirezmalule degradationkineticsofclavulanicacidinfermentationbrothsatlowtemperatures AT peterneubauer degradationkineticsofclavulanicacidinfermentationbrothsatlowtemperatures AT stefanjunne degradationkineticsofclavulanicacidinfermentationbrothsatlowtemperatures AT rigobertoriosestepa degradationkineticsofclavulanicacidinfermentationbrothsatlowtemperatures |
_version_ |
1725781660324069376 |