A statistical approach using L25 orthogonal array method to study fermentative production of clavulanic acid by Streptomyces clavuligerus MTCC 1142
Abstract
Clavulanic acid is a naturally occurring antibiotic produced by Streptomyces clavuligerus. The present work reports on clavulanic acid production by Streptomyces clavuligerus MTCC 1142 using one-factor-at-a-time and L(25) orthogonal array. The one-factor-at-a-time method was adopted to investigate the effect of media components (i.e., carbon source, nitrogen source and inoculum concentration) and environmental factors such as pH for clavulanic acid production. Production of clavulanic acid by Streptomyces clavuligerus was investigated using seven different carbon sources (viz. glucose, sucrose, modified starch, rice-bran oil, soybean oil, palm oil, and glycerol) and six different nitrogen sources (viz. peptone, yeast extract, ammonium chloride, ammonium carbonate, sodium nitrate and potassium nitrate). A maximum yield of 140 microg/mL clavulanic acid was obtained in the medium containing soybean oil as a carbon source and yeast extract as nitrogen source. Subsequently, the concentration of soybean flour, soybean oil, dextrin, yeast extract and K2HPO4 were optimized using L25 orthogonal array method. The final optimized medium produced 500 microg/mL clavulanic acid at the end of 96 h as compared to 140 microg/mL before optimization. Synthesis of precursor molecules as a metabolic driving force is of considerable importance in antibiotic synthesis. Attempts to increase the clavulanic acid synthesis by manipulating the anaplerotic flux on C(3) and C(5) precursors by supplementin…
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The pH of fermentation media has a profound effect on clavulanic acid yield.
“Furthermore, the pH of fermentation media was described as having a profound effect on clavulanic acid yield (Saudagar and Singhal, 2007a; Salem-Berkhit et al., 2010).”
From Fermentation Conditions that Affect Clavulanic Acid Production in Streptomyces clavuligerus: A Systematic Review (2016) · cites this paper as Saudagar and Singhal, 2007a
Basal media containing glycerol exhibited higher maximum amounts of clavulanic acid compared to starch.
“On the contrary, two studies reported a totally different observation—basal media containing glycerol exhibited higher maximum amounts of clavulanic acid as compared to starch (Saudagar and Singhal, 2007a; Bellão et al., 2013).”
From Fermentation Conditions that Affect Clavulanic Acid Production in Streptomyces clavuligerus: A Systematic Review (2016) · cites this paper as Saudagar and Singhal, 2007a
Recent studies supported Romero et al. (1986), finding higher clavulanic acid amounts in media supplemented with different concentrations of arginine compared to ornithine.
“Nevertheless, recent studies supported the results of Romero et al. (1986); where higher amounts of clavulanic acid were seen in media supplemented with different concentrations of arginine compared to ornithine (Saudagar and Singhal, 2007a,b).”
From Fermentation Conditions that Affect Clavulanic Acid Production in Streptomyces clavuligerus: A Systematic Review (2016) · cites this paper as Saudagar and Singhal, 2007a,b
Glycerol shows a biphasic dose response, with clavulanic acid production inhibited at concentrations that are either too high or too low.
“Additionally, two other studies by Chen et al. (2002) and Saudagar and Singhal (2007a) revealed a biphasic dose response of glycerol; whereby clavulanic acid production was inhibited at concentrations which were either too high or too low.”
From Fermentation Conditions that Affect Clavulanic Acid Production in Streptomyces clavuligerus: A Systematic Review (2016) · cites this paper as Saudagar and Singhal (2007a)
Saudagar and Singhal (2007a) observed similar concentrations of clavulanic acid in media containing palm oil and soybean oil.
“These results were consistent with a study by Saudagar and Singhal (2007a), as similar concentrations of clavulanic acid was observed in media containing palm oil and soybean oil.”
From Fermentation Conditions that Affect Clavulanic Acid Production in Streptomyces clavuligerus: A Systematic Review (2016) · cites this paper as Saudagar and Singhal (2007a)
Saudagar and Singhal (2007a) suggested optimum concentrations of soybean flour (8.8%), soybean oil (1.2%), dextrin (1.0%), yeast extract (1.5%), and KH2PO4 (0.2%), with an optimal pH of 7.0 ± 0.2.
“By using the L25 orthogonal array method, the study suggested optimum concentrations of soybean flour (8.8%), soybean oil (1.2%), dextrin (1.0%), yeast extract (1.5%), and KH2PO4 (0.2%); with an optimal pH of 7.0 ± 0.2.”
From Fermentation Conditions that Affect Clavulanic Acid Production in Streptomyces clavuligerus: A Systematic Review (2016) · cites this paper as Saudagar and Singhal (2007a)
Saudagar and Singhal (2007a) designed a fermentation media using the L25 orthogonal array method to optimize clavulanic acid production.
“Meanwhile, Saudagar and Singhal (2007a) designed a slightly different fermentation media by undertaking another statistical approach to optimize fermentation media for clavulanic acid production.”
From Fermentation Conditions that Affect Clavulanic Acid Production in Streptomyces clavuligerus: A Systematic Review (2016) · cites this paper as Saudagar and Singhal (2007a)
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- Authors
- Saudagar, P. S., & Singhal, R. S.
- Affiliations
- Institute of Chemical Technology (IN)
- Corresponding author
- Singhal, Rekha S.
- Venue
- Applied Biochemistry and Biotechnology
- Published
- 2007-03
- Volume
- 136
- Issue
- 3
- Pages
- 345-359
- ISSN
- 0273-2289 (ISSN-L)
- 1559-0291
- OpenAlex
- W2041528665
- Cited by
- 26
- References
- 23
- Citations by year
- 2026: 2 · 2024: 1 · 2022: 2 · 2019: 1 · 2018: 1 · 2016: 1 · 2015: 3 · 2014: 3 · 2013: 2 · 2012: 3
- FWCI
- 1.11
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Applied Biochemistry and Biotechnology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University Grants Commission
- Topics
- Health Sciences › Medicine › Pharmacology › Microbial Natural Products and Biosynthesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial Metabolic Engineering and Bioproduction
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Enzyme Production and Characterization
- Keywords
- clavulanic acid, Streptomyces clavuligerus, fermentation production, culture medium optimization, carbon source, nitrogen source, inoculum size, pH optimization, arginine supplementation, leucine supplementation, antibiotic production
- MeSH terms
- Amino Acids, Anti-Bacterial Agents, Biotechnology, Carbon, Culture Media, Fermentation, Hydrogen-Ion Concentration, Nitrogen, Soybean Oil, Streptomyces, Clavulanic Acid
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