Application of Acid and Cold Stresses to Enhance the Production of Clavulanic Acid by Streptomyces clavuligerus
Clavulanic acid (CA) is frequently prescribed for treatment of bacterial infections. Despite the large number of studies concerning CA production, there is still a need to search for more effective and productive processes because it is mainly produced by biochemical route and is chemically unstable...
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| Published in: | Applied biochemistry and biotechnology Vol. 188; no. 3; pp. 706 - 719 |
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| Main Authors: | , , , , , |
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| Language: | English |
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01-07-2019
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| Abstract | Clavulanic acid (CA) is frequently prescribed for treatment of bacterial infections. Despite the large number of studies concerning CA production, there is still a need to search for more effective and productive processes because it is mainly produced by biochemical route and is chemically unstable. This paper evaluates the influence of acid and cold stresses on CA production by
Streptomyces clavuligerus
in bench scale stirred tank bioreactor. Four batch cultures were conducted at constant pH (6.8 or 6.3) and temperature (30, 25, or 20 °C) and five batch cultures were performed with application of acid stress (pH reduction from 6.8 to 6.3), cold stress (reduction from 30 to 20 °C), or both. The highest maximum CA concentration (684.4 mg L
−1
) was obtained in the culture conducted at constant temperature of 20 °C. However, the culture under acid stress, in which the pH was reduced from 6.8 to 6.3 at a rate of 0.1 pH unit every 6 h, provided the most promising result, exhibiting a global yield coefficient of CA relative to cell formation (
Y
CA/X
) of 851.1 mg
CA
g
X
−1
. High
Y
CA/X
values indicate that a small number of cells are able to produce a large amount of antibiotic with formation of smaller amounts of side byproducts. This could be especially attractive for decreasing the complexity and cost of the downstream processing, enhancing CA production. |
|---|---|
| AbstractList | Clavulanic acid (CA) is frequently prescribed for treatment of bacterial infections. Despite the large number of studies concerning CA production, there is still a need to search for more effective and productive processes because it is mainly produced by biochemical route and is chemically unstable. This paper evaluates the influence of acid and cold stresses on CA production by Streptomyces clavuligerus in bench scale stirred tank bioreactor. Four batch cultures were conducted at constant pH (6.8 or 6.3) and temperature (30, 25, or 20 °C) and five batch cultures were performed with application of acid stress (pH reduction from 6.8 to 6.3), cold stress (reduction from 30 to 20 °C), or both. The highest maximum CA concentration (684.4 mg L−1) was obtained in the culture conducted at constant temperature of 20 °C. However, the culture under acid stress, in which the pH was reduced from 6.8 to 6.3 at a rate of 0.1 pH unit every 6 h, provided the most promising result, exhibiting a global yield coefficient of CA relative to cell formation (YCA/X) of 851.1 mgCA gX−1. High YCA/X values indicate that a small number of cells are able to produce a large amount of antibiotic with formation of smaller amounts of side byproducts. This could be especially attractive for decreasing the complexity and cost of the downstream processing, enhancing CA production. Clavulanic acid (CA) is frequently prescribed for treatment of bacterial infections. Despite the large number of studies concerning CA production, there is still a need to search for more effective and productive processes because it is mainly produced by biochemical route and is chemically unstable. This paper evaluates the influence of acid and cold stresses on CA production by Streptomyces clavuligerus in bench scale stirred tank bioreactor. Four batch cultures were conducted at constant pH (6.8 or 6.3) and temperature (30, 25, or 20 °C) and five batch cultures were performed with application of acid stress (pH reduction from 6.8 to 6.3), cold stress (reduction from 30 to 20 °C), or both. The highest maximum CA concentration (684.4 mg L −1 ) was obtained in the culture conducted at constant temperature of 20 °C. However, the culture under acid stress, in which the pH was reduced from 6.8 to 6.3 at a rate of 0.1 pH unit every 6 h, provided the most promising result, exhibiting a global yield coefficient of CA relative to cell formation ( Y CA/X ) of 851.1 mg CA g X −1 . High Y CA/X values indicate that a small number of cells are able to produce a large amount of antibiotic with formation of smaller amounts of side byproducts. This could be especially attractive for decreasing the complexity and cost of the downstream processing, enhancing CA production. Clavulanic acid (CA) is frequently prescribed for treatment of bacterial infections. Despite the large number of studies concerning CA production, there is still a need to search for more effective and productive processes because it is mainly produced by biochemical route and is chemically unstable. This paper evaluates the influence of acid and cold stresses on CA production by Streptomyces clavuligerus in bench scale stirred tank bioreactor. Four batch cultures were conducted at constant pH (6.8 or 6.3) and temperature (30, 25, or 20 °C) and five batch cultures were performed with application of acid stress (pH reduction from 6.8 to 6.3), cold stress (reduction from 30 to 20 °C), or both. The highest maximum CA concentration (684.4 mg L ) was obtained in the culture conducted at constant temperature of 20 °C. However, the culture under acid stress, in which the pH was reduced from 6.8 to 6.3 at a rate of 0.1 pH unit every 6 h, provided the most promising result, exhibiting a global yield coefficient of CA relative to cell formation (Y ) of 851.1 mg g . High Y values indicate that a small number of cells are able to produce a large amount of antibiotic with formation of smaller amounts of side byproducts. This could be especially attractive for decreasing the complexity and cost of the downstream processing, enhancing CA production. |
| Author | Costa, C. L. L. Badino, A. C. Cerri, M. O. Pereira, J. F. B. Pedrolli, D. B. Rodrigues, K. C. S. |
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| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/30680701$$D View this record in MEDLINE/PubMed |
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| CitedBy_id | crossref_primary_10_1007_s42770_024_01306_0 crossref_primary_10_1016_j_biortech_2023_129268 crossref_primary_10_1080_10826068_2021_2009860 crossref_primary_10_1007_s00248_019_01443_2 crossref_primary_10_1007_s00449_021_02555_1 crossref_primary_10_3390_antibiotics10010084 crossref_primary_10_1002_bbb_2294 |
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| Keywords | Stress induction Cold stress Acid stress Clavulanic acid Process enhancing Batch fermentation Streptomyces clavuligerus |
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| Snippet | Clavulanic acid (CA) is frequently prescribed for treatment of bacterial infections. Despite the large number of studies concerning CA production, there is... |
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| SubjectTerms | Acids Antibiotics Bacterial diseases Biochemistry Bioreactors Biotechnology Cell culture Chemistry Chemistry and Materials Science Clavulanic acid Organic chemistry pH effects Reduction Streptomyces clavuligerus Stresses |
| Title | Application of Acid and Cold Stresses to Enhance the Production of Clavulanic Acid by Streptomyces clavuligerus |
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