Utilization of ornithine and arginine as specific precursors of clavulanic acid
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Ornithine and arginine (5 to 20 mM), but not glutamic acid or proline, exerted a concentration-dependent stimulatory effect on the biosynthesis of clavulanic acid in both resting-cell cultures and long-term fermentations of Streptomyces clavuligerus. Ornithine strongly inhibited cephamycin biosynthesis in the same strain. [1-14C]-, [5-14C]-, or [U-14 C] ornithine was efficiently incorporated into clavulanic acid, whereas the incorporation of uniformly labeled glutamic acid was very poor. [U-14C] citrulline were not incorporated at all. Mutant nca-1, a strain that is blocked in clavulanic acid biosynthesis, did not incorporate arginine into clavulanic acid. S. clavuligerus showed arginase activity, converting arginine into ornithine, but not amidinotransferase activity. Both arginase activity and clavulanic acid formation were enhanced simultaneously by supplementing the production medium with 10 mM arginine.
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Two important precursors for clavulanic acid are arginine (C5 precursor) and glutaraldehyde-3-phosphate (C3 precursor).
“These efforts then resulted in the identification of two important precursors for clavulanic acid—arginine (C5 precursor) and glutaraldehyde-3-phosphate (C3 precursor) (Romero et al., 1986; Kanehisa and Goto, 2000; Kanehisa et al., 2016).”
From Fermentation Conditions that Affect Clavulanic Acid Production in Streptomyces clavuligerus: A Systematic Review (2016) · cites this paper as Romero et al., 1986
Romero et al. (1986) reported maximum clavulanic acid concentrations of 16 μg/dry weight biomass with arginine and 9 μg/dry weight biomass with ornithine.
“Romero et al. (1986) reported maximum concentrations of clavulanic acid in a slightly different manner, where 16 μg/dry weight of biomass was observed with arginine; while 9 μg/dry weight of biomass was observed with ornithine.”
From Fermentation Conditions that Affect Clavulanic Acid Production in Streptomyces clavuligerus: A Systematic Review (2016) · cites this paper as Romero et al. (1986)
Addition of arginine or ornithine in fermentation media would increase the flow of C5 precursors into the biosynthesis pathway, which would subsequently increase clavulanic acid production.
“Thus, the addition of arginine or ornithine in fermentation media would increase the flow of C5 precursors into the biosynthesis pathway, which then subsequently increase the production of clavulanic acid (Romero et al., 1986; Lynch and Yang, 2004).”
From Fermentation Conditions that Affect Clavulanic Acid Production in Streptomyces clavuligerus: A Systematic Review (2016) · cites this paper as Romero et al., 1986
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Primary metabolism and its control in streptomycetes: A most unusual group of bacteria
Hodgson, D. A. (2000) · Advances in Microbial Physiology · doi:10.1016/s0065-2911(00)42003-5 · Cited by 267 · see citing works
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
“Thus, the addition of arginine or ornithine in fermentation media would increase the flow of C5 precursors into the biosynthesis pathway, which then subsequently increase the production of clavulanic acid (Romero et al., 1986; Lynch and Yang, 2004).”
BackgroundMethodResultInfluentialSaudagar, P. S., & Singhal, R. S. (2007) · Applied Biochemistry and Biotechnology · doi:10.1007/s12010-007-9030-x · Cited by 26 · see citing works
- Authors
- Romero, J., Liras, P., & Martín, J. F.
- ORCID
- Liras, P
- Venue
- Applied and Environmental Microbiology
- Publisher
- American Society for Microbiology
- Published
- 1986-10
- Volume
- 52
- Issue
- 4
- Pages
- 892-897
- ISSN
- 0099-2240 (ISSN-L)
- 1098-5336
- PMC
- PMC239133
- OpenAlex
- W2148393598
- Cited by
- 74
- References
- 0
- Citations by year
- 2023: 1 · 2022: 1 · 2021: 3 · 2020: 1 · 2019: 1 · 2018: 3 · 2016: 3 · 2015: 2 · 2014: 2 · 2013: 2 · 2012: 5
- FWCI
- 1.59
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Applied and Environmental Microbiology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Microbial Natural Products and Biosynthesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Microbial Metabolism and Applications
- Keywords
- clavulanic acid biosynthesis, ornithine, L-arginine, Streptomyces clavuligerus, arginase activity, amino acid precursors, carbon-14 incorporation, antibiotic production
- MeSH terms
- Arginine, Cephamycins, Clavulanic Acids, Glutamates, Ornithine, Proline, Streptomyces, Glutamic Acid
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