Manipulation of the physiology of clavulanic acid production in Streptomyces clavuligerus
Abstract
This paper reports a novel use of cluster analysis for the identification of intermediary metabolites that are produced at rates closely correlated with those of antibiotic biosynthesis. This information was used to devise culture feeds resulting in enhanced production of clavulanic acid, an antibiotic of current worldwide commercial interest. The feeding strategies apparently alleviated a rate-limiting supply of the C3 precursor of clavulanic acid. C3 limitation may be a consequence of unusual nitrogen and carbon metabolism in Streptomyces clavuligerus. This approach has potential as a generic method for influencing biosynthetic pathway fluxes using feeds without knowledge of the biosynthetic pathway.
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In Ives and Bushell (1997), no clavulanic acid production was observed in glycerol-containing C-limited media.
“Similar findings were also reported by Ives and Bushell (1997) where no production of clavulanic acid was observed in glycerol-containing C-limited media.”
From Fermentation Conditions that Affect Clavulanic Acid Production in Streptomyces clavuligerus: A Systematic Review (2016) · cites this paper as Ives and Bushell (1997)
Supplementation of L-threonine prevents anaplerotic flux on pyruvate to synthesize amino acids such as isoleucine, which increases availability of C3 precursors and eventually enhances clavulanic acid production.
“Indeed the supplementation of L-threonine was found to prevent the anaplerotic flux on pyruvate to synthesize amino acids such as isoleucine, which in turn increased the availability of C3 precursors and eventually enhanced clavulanic acid production (Ives and Bushell, 1997; Bushell et al., 2006; Saudagar and Singhal, 2007b).”
From Fermentation Conditions that Affect Clavulanic Acid Production in Streptomyces clavuligerus: A Systematic Review (2016) · cites this paper as Ives and Bushell, 1997
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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 · see citing works
“…L-threonine was found to prevent the anaplerotic flux on pyruvate to synthesize amino acids such as isoleucine, which in turn increased the availability of C3 precursors and eventually enhanced clavulanic acid production (Ives and Bushell, 1997; Bushell et al., 2006; Saudagar and Singhal, 2007b).”
BackgroundResultSaudagar, P. S., & Singhal, R. S. (2007) · Applied Biochemistry and Biotechnology · doi:10.1007/s12010-007-9030-x · Cited by 26 · see citing works
- Authors
- Ives, P. R., & Bushell, M. E.
- Affiliations
- University of Surrey (GB)
- ORCID
- Bushell, Michael E.
- Venue
- Microbiology
- Publisher
- Microbiology Society
- Published
- 1997-11-01
- Volume
- 143
- Issue
- 11
- Pages
- 3573-3579
- ISSN
- 1350-0872 (ISSN-L)
- 1465-2080
- OpenAlex
- W2151420444
- Cited by
- 50
- References
- 0
- Citations by year
- 2024: 1 · 2022: 1 · 2019: 2 · 2018: 3 · 2016: 2 · 2015: 1 · 2014: 1 · 2013: 3 · 2012: 2
- FWCI
- 1.13
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Microbiology (publishedVersion)
- PubMed (publishedVersion)
- Open Research (University of Surrey) (submittedVersion)
- Surrey Research Insight Open Access (The University of Surrey) (submittedVersion)
- 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 › Microbial Metabolism and Applications
- Keywords
- clavulanic acid, Streptomyces clavuligerus, antibiotic biosynthesis, intermediary metabolites, clustering, nitrogen metabolism, carbon metabolism, secondary metabolite production
- MeSH terms
- Amino Acids, Ammonium Chloride, Anti-Bacterial Agents, Culture Media, Models, Chemical, Streptomyces, Cluster Analysis, Bioreactors, Clavulanic Acid
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