Overproduction of clavulanic acid by extractive fermentation

Background: Clavulanic acid is an important beta-lactamase inhibitor produced as a secondary metabolite by the actinomycete Streptomyces clavuligerus. Clavulanic acid is chemically unstable; therefore, it is degraded during bacterial cultivation. In this work, the adsorbents clinoptilolite, activate...

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Main Authors: Cecília Ladeira Lopes Costa, Alberto Colli Badino
Format: Article
Language:English
Published: Elsevier 2015-05-01
Series:Electronic Journal of Biotechnology
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0717345815000378
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author Cecília Ladeira Lopes Costa
Alberto Colli Badino
author_facet Cecília Ladeira Lopes Costa
Alberto Colli Badino
author_sort Cecília Ladeira Lopes Costa
collection DOAJ
description Background: Clavulanic acid is an important beta-lactamase inhibitor produced as a secondary metabolite by the actinomycete Streptomyces clavuligerus. Clavulanic acid is chemically unstable; therefore, it is degraded during bacterial cultivation. In this work, the adsorbents clinoptilolite, activated carbon, calcined hydrotalcite, and Amberlite IRA 400 anionic exchange resin were studied in terms of their ability to adsorb clavulanic acid during extractive fermentation, in order to prevent product degradation and avoid product concentrations reaching inhibitory levels. Adsorption assays were used to investigate the effect of pH, and the decrease in the clavulanic acid concentration in the culture broth was measured for each adsorbent. Results: IRA 400 was found to be most effective, with 78% adsorption of clavulanic acid. The maximum production of clavulanic acid in Erlenmeyer flask cultures increased 86% in terms of mass of CA, and 248% in cumulative CA concentration, with the use of Amberlite IRA 400 as adsorbent in extractive fermentation, compared to control fermentation performed without product removal. Conclusions: The results indicated that extractive fermentation using a solid phase could be an important way of enhancing clavulanic acid titers. It was also possible to show that clavulanic acid acts as an inhibitor of its own synthesis.
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spelling doaj.art-da58330b6204424fbc229994559c19862022-12-21T18:55:03ZengElsevierElectronic Journal of Biotechnology0717-34582015-05-0118315416010.1016/j.ejbt.2015.03.001Overproduction of clavulanic acid by extractive fermentationCecília Ladeira Lopes CostaAlberto Colli BadinoBackground: Clavulanic acid is an important beta-lactamase inhibitor produced as a secondary metabolite by the actinomycete Streptomyces clavuligerus. Clavulanic acid is chemically unstable; therefore, it is degraded during bacterial cultivation. In this work, the adsorbents clinoptilolite, activated carbon, calcined hydrotalcite, and Amberlite IRA 400 anionic exchange resin were studied in terms of their ability to adsorb clavulanic acid during extractive fermentation, in order to prevent product degradation and avoid product concentrations reaching inhibitory levels. Adsorption assays were used to investigate the effect of pH, and the decrease in the clavulanic acid concentration in the culture broth was measured for each adsorbent. Results: IRA 400 was found to be most effective, with 78% adsorption of clavulanic acid. The maximum production of clavulanic acid in Erlenmeyer flask cultures increased 86% in terms of mass of CA, and 248% in cumulative CA concentration, with the use of Amberlite IRA 400 as adsorbent in extractive fermentation, compared to control fermentation performed without product removal. Conclusions: The results indicated that extractive fermentation using a solid phase could be an important way of enhancing clavulanic acid titers. It was also possible to show that clavulanic acid acts as an inhibitor of its own synthesis.http://www.sciencedirect.com/science/article/pii/S0717345815000378AdsorptionClavulanic acidExtractive fermentationIntegrated processingProduct inhibition
spellingShingle Cecília Ladeira Lopes Costa
Alberto Colli Badino
Overproduction of clavulanic acid by extractive fermentation
Electronic Journal of Biotechnology
Adsorption
Clavulanic acid
Extractive fermentation
Integrated processing
Product inhibition
title Overproduction of clavulanic acid by extractive fermentation
title_full Overproduction of clavulanic acid by extractive fermentation
title_fullStr Overproduction of clavulanic acid by extractive fermentation
title_full_unstemmed Overproduction of clavulanic acid by extractive fermentation
title_short Overproduction of clavulanic acid by extractive fermentation
title_sort overproduction of clavulanic acid by extractive fermentation
topic Adsorption
Clavulanic acid
Extractive fermentation
Integrated processing
Product inhibition
url http://www.sciencedirect.com/science/article/pii/S0717345815000378
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