Genome‐wide gene expression changes in an industrial clavulanic acid overproduction strain of Streptomyces clavuligerus
Open accessAbstract
Summary: To increase production of the important pharmaceutical compound clavulanic acid, a β‐lactamase inhibitor, both random mutagenesis approaches and rational engineering of Streptomyces clavuligerus strains have been extensively applied. Here, for the first time, we compared genome‐wide gene expression of an industrial S. clavuligerus strain, obtained through iterative mutagenesis, with that of the wild‐type strain. Intriguingly, we found that the majority of the changes contributed not to a complex rewiring of primary metabolism but consisted of a simple upregulation of various antibiotic biosynthesis gene clusters. A few additional transcriptional changes in primary metabolism at key points seem to divert metabolic fluxes to the biosynthetic precursors for clavulanic acid. In general, the observed changes largely coincide with genes that have been targeted by rational engineering in recent years, yet the presence of a number of previously unexplored genes clearly demonstrates that functional genomic analysis can provide new leads for strain improvement in biotechnology.
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Researchers have identified numerous genes involved in clavulanic acid biosynthesis in S. clavuligerus, including the clavaminate synthases genes.
“With the advancement of next generation sequencing technologies, researchers have identified numerous genes involved in clavulanic acid biosynthesis in S. clavuligerus including the clavaminate synthases genes (Medema et al., 2011).”
From Fermentation Conditions that Affect Clavulanic Acid Production in Streptomyces clavuligerus: A Systematic Review (2016) · cites this paper as Medema et al., 2011
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Research works printed but not linked: 20
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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
“With the advancement of next generation sequencing technologies, researchers have identified numerous genes involved in clavulanic acid biosynthesis in S. clavuligerus including the clavaminate synthases genes (Medema et al., 2011).”
Background
- Authors
- Medema, M. H., Alam, M. T., Heijne, W. H. M., van den Berg, M. A., Müller, U., Trefzer, A., Bovenberg, R. A. L., Breitling, R., & Takano, E.
- Affiliations
- University of Groningen (NL)
- DSM (Netherlands) (NL)
- Venue
- Microbial Biotechnology
- Publisher
- Wiley
- Published
- 2010-11-02
- Volume
- 4
- Issue
- 2
- Pages
- 300-305
- ISSN
- 1751-7915 (ISSN-L)
- PMC
- PMC3818869
- OpenAlex
- W1968483410
- Cited by
- 57
- References
- 0
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 6 · 2020: 2 · 2019: 4 · 2018: 5 · 2017: 1 · 2016: 5 · 2015: 6 · 2014: 6 · 2013: 5 · 2012: 8
- FWCI
- 3.77
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Microbial Biotechnology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
- Radboud Repository (Radboud University) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion, other-oa)
- University of Warwick (cc-by)
- Funders
- Rijksuniversiteit Groningen
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek
- Stichting voor de Technische Wetenschappen (STW 10463, 10463)
- 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 › Genetics › Bacterial Genetics and Biotechnology
- Keywords
- clavulanic acid, Streptomyces clavuligerus, gene expression, transcriptome, beta-lactamase inhibitors, secondary metabolite production, random mutagenesis, synthetic biology, natural products
- MeSH terms
- Bacterial Proteins, Industrial Microbiology, Streptomyces, Gene Expression Regulation, Bacterial, Genome, Bacterial, Clavulanic Acid
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