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A study on clavulanic acid production by Streptomyces clavuligerus in batch, fed-batch and continuous processes
Open accessAbstract
Clavulanic acid (CA) is a potent inhibitor of beta-lactamases, enzymes that are responsible for the hydrolysis of beta-lactam antibiotics. It is a secondary metabolite produced by the filamentous aerobic bacterium Streptomyces clavuligerus in submerged cultivations. In the present work clavulanic acid production in batch, fed-batch and continuous bioreactors was studied with the objective of increasing productivity. The operating conditions: temperature, aeration and agitation, were the same in all cases, 28º C, 0.5 vvm and 800 rpm, respectively. The CA concentration obtained in the fed-batch culture, 404 mg L-1, was ca twice the value obtained in the batch culture, 194 mg L-1, while 293 mg L-1 was obtained in the continuous culture. The highest productivity was obtained in the continuous cultivation, 10.6 mg L-1 h-1, as compared with 8.8 mg L-1 h-1 in the fed-batch process and 3.5 mg L-1 h-1 in the batch process, suggesting that continuous culture of Streptomyces clavuligerus is a promising strategy for clavulanic acid production.
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“Previous studies have shown that CA stability increases at slightly acidic pH values [10,11]; several authors found a pH of 6.8 as favorable for obtaining high titers of CA in submerged cultures [5,7,9,12,13,14,15,16].”
From Degradation Kinetics of Clavulanic Acid in Fermentation Broths at Low Temperatures (2019) · cites this paper as [9]
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“Comparing batch and fed-batch fermentation, fed-batch fermentation systems seemed to generate a higher yield of clavulanic acid (Chen et al., 2002; Neto et al., 2005; Bellão et al., 2013).”
From Fermentation Conditions that Affect Clavulanic Acid Production in Streptomyces clavuligerus: A Systematic Review (2016) · cites this paper as Neto et al., 2005
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Cites
Naturally-occurring beta-lactamase inhibitors with antibacterial activity
BROWN, A. G., BUTTERWORTH, D., COLE, M., HANSCOMB, G., HOOD, J. D., READING, C., & ROLINSON, G. N. (1976) · The Journal of Antibiotics · doi:10.7164/antibiotics.29.668 · Cited by 399
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Research works printed but not linked: 10
- Baggaley, K.H., Brown, A.G. and Schofield, C.J., Chemistry and Biosynthesis of Clavulanic Acid and Another Clavans. Natural Product Report, vol. 57, pp. 309-333, 1997.
- Baptista-Neto, A., Gouveia, E.R., Badino-Jr, A.C. and Hokka, C.O., Phenomenological Model of the Clavulanic Acid Production Process Utilizing Streptomyces clavuligerus, Brazilian Journal of Chemical Engineering, vol. 17, n. 04-07, pp.809- 818, 2000.
- Battaglia-Hirata, D., Produção de Ácido Clavulânico por Streptomyces clavuligerus e Extração em Sistema de Duas Fases Aquosas, São Carlos-SP, University Federal of São Carlos, (Master's thesis), 2003.
- Butterworth, D., Clavulanic acid: Properties Biosynthesis, and Fermentation. In: Vandamme, E.J. Biotechnology of Industrial Antibiotics, New York, Marcel Dekker, vol.22, pp.225-235, 1984.
- Demain, A.L, Overproduction of Microbial Metabolites and Enzymes due to Alteration of Regulation, Advances in Biotechnological Engineering, vol. 1, 113 p., (1971)
- Foulstone, M. and Reading, C., Assay of Amoxillin and Clavulanic Acid, the Components of Augmentin, in Biological Fluids With HPLC, Ant. Ag. Chem., vol.22, pp.753-762, 1982.
- Kirk S, Avignone-Rossa C.A. and Bushell M.E., Growth Limiting Substrate Affects Antibiotic Production and Associated Metabolic Fluxes in Streptomyces clavuligerus, Biotechnology Letters; vol. 22; n. 22, pp. 1803-1809; 2000.
- Mayer, A.F. and Deckwer, W.-D. Simultaneous Production and Decomposition of Clavulanic Acid During Streptomyces clavuligerus Cultivations. Appl. Microbiol. Biotechnol., vol.45, pp. 41-46, 1996.
- Rosa, J.C., Influência das Condições de Transferência de O2 na Produção de Ácido Clavulânico por Streptomyces clavuligerus, São Carlos-SP, University Federal of São Carlos, (Master's thesis), 2002.
- Yegneswaran, P.K., Gray, M.R. and Thompson, B.G., Experimental Simulation of Dissolved Oxigen Flutuations in Large Fermentors: Effect on Streptomyces clavuligerus, Biotech. Bio., vol.38, pp. 1203-1209, 1991.
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Ser, H.-L., Law, J. W.-F., Chaiyakunapruk, N., Jacob, S. A., Palanisamy, U. D., Chan, K.-G., Goh, B.-H., & Lee, L.-H. (2016) · Frontiers in Microbiology · doi:10.3389/fmicb.2016.00522 · Cited by 90
“Comparing batch and fed-batch fermentation, fedbatch fermentation systems seemed to generate a higher yield of clavulanic acid (Chen et al., 2002; Neto et al., 2005; Bellão et al., 2013).”
BackgroundDegradation Kinetics of Clavulanic Acid in Fermentation Broths at Low Temperatures
Gómez-Ríos, D., Ramírez-Malule, H., Neubauer, P., Junne, S., & Ríos-Estepa, R. (2019) · Antibiotics · doi:10.3390/antibiotics8010006 · Cited by 17
Metadata
- Authors
- Neto, A. B., Hirata, D. B., Cassiano Filho, L. C. M., Bellão, C., Badino Júnior, A. C., & Hokka, C. O.
- Affiliations
- Universidade Federal de São Carlos (BR)
- Federal University of São Carlos, Brazil
- Venue
- Brazilian Journal of Chemical Engineering
- Publisher
- FapUNIFESP (SciELO)
- Published
- 2005-12
- Volume
- 22
- Issue
- 4
- Pages
- 557-563
- ISSN
- 0104-6632 (ISSN-L)
- OpenAlex
- W2136136263
- Cited by
- 23
- References
- 1
- Citations by year
- 2024: 1 · 2022: 1 · 2021: 3 · 2020: 2 · 2019: 1 · 2018: 1 · 2017: 2 · 2016: 1 · 2014: 1 · 2013: 2 · 2012: 3
- FWCI
- 0.21
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Brazilian Journal of Chemical Engineering (publishedVersion, cc-by-nc)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (publishedVersion, other-oa)
- Americanae (AECID Library) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Fundação de Amparo à Pesquisa do Estado de São Paulo (99/03279-7)
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Topics
- Life Sciences › Immunology and Microbiology › Applied Microbiology and Biotechnology › Microbial Natural Products and Biosynthesis
- Physical Sciences › Chemical Engineering › Fluid Flow and Transfer Processes › Fluid Dynamics and Mixing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Enzyme Production and Characterization
- Keywords
- clavulanic acid, Streptomyces clavuligerus, secondary metabolite production, continuous fermentation, fed-batch fermentation, batch fermentation, bioprocess productivity, submerged culture, beta-lactamase inhibitors
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