ArticleApplied and environmental microbiology2015
The Pathway-Specific Regulator ClaR of Streptomyces clavuligerus Has a Global Effect on the Expression of Genes for Secondary Metabolism and Differentiation.
Article in Applied and environmental microbiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- An integrative-omics analysis of an industrial clavulanic acid-overproducing Streptomyces clavuligerus.Applied microbiology and biotechnology · 2022Article
- A TetR family transcriptional regulator, SP_2854 can affect the butenyl-spinosyn biosynthesis by regulating glucose metabolism in Saccharopolyspora pogona.Microbial cell factories · 2022Article
- Streptomyces clavuligerus: The Omics Era.Journal of industrial microbiology & biotechnology · 2021Article
- Clavulanic Acid Production byAntibiotics (Basel, Switzerland) · 2021Review
- Cloning and Overexpression of theFrontiers in microbiology · 2020Article
- Comparative Transcriptome Analysis ofAntibiotics (Basel, Switzerland) · 2019Article
- Regulation of Geldanamycin Biosynthesis by Cluster-Situated Transcription Factors and the Master Regulator PhoP.Antibiotics (Basel, Switzerland) · 2019Review
- Dissolution of the Disparate: Co-ordinate Regulation in Antibiotic Biosynthesis.Antibiotics (Basel, Switzerland) · 2019Review
- Comparative Genomics and Metabolomics Analyses of Clavulanic Acid-ProducingFrontiers in microbiology · 2019Article
- Activation of Secondary Metabolite Gene Clusters inFrontiers in microbiology · 2019Article
- The CagRS Two-Component System Regulates Clavulanic Acid Metabolism via Multiple Pathways inFrontiers in microbiology · 2019Article
- Transcriptional Studies on aApplied and environmental microbiology · 2018Article
- Unraveling Nutritional Regulation of Tacrolimus Biosynthesis inAntibiotics (Basel, Switzerland) · 2018Review
- Discovering the potential of S. clavuligerus for bioactive compound production: cross-talk between the chromosome and the pSCL4 megaplasmid.BMC genomics · 2017Article
- Key role of LaeA and velvet complex proteins on expression of β-lactam and PR-toxin genes in Penicillium chrysogenum: cross-talk regulation of secondary metabolite pathways.Journal of industrial microbiology & biotechnology · 2017Review
- Proteome-wide alterations in an industrial clavulanic acid producing strain ofSynthetic and systems biotechnology · 2017Article
- Proteomics analysis of global regulatory cascades involved in clavulanic acid production and morphological development in Streptomyces clavuligerus.Journal of industrial microbiology & biotechnology · 2016Article
- Multiple and Variable NHEJ-Like Genes Are Involved in Resistance to DNA Damage inFrontiers in microbiology · 2016Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Streptomyces clavuligerus claR::aph is a claR-defective mutant, but in addition to its claR defect it also carries fewer copies of the resident linear plasmids pSCL2 and pSCL4 (on the order of 4 × 10(5)-fold lower than the wild-type strain), as shown by qPCR. To determine the function of ClaR without potential interference due to plasmid copy number, a new strain, S. clavuligerus ΔclaR::aac, with claR deleted and carrying the wild-type level of plasmids, was constructed. Transcriptomic analyses were performed in S. clavuligerus ΔclaR::aac and S. clavuligerus ATCC 27064 as the control strain. The new ΔclaR mutant did not produce clavulanic acid (CA) and showed a partial expression of genes for the early steps of the CA biosynthesis pathway and a very poor expression (1 to 8%) of the genes for the late steps of the CA pathway. Genes for cephamycin C biosynthesis were weakly upregulated (1.7-fold at 22.5 h of culture) in the ΔclaR mutant, but genes for holomycin biosynthesis were expressed at levels from 3- to 572-fold higher than in the wild-type strain, supporting the observed overproduction of holomycin by S. clavuligerus ΔclaR::aac. Interestingly, three secondary metabolites produced by gene clusters SMCp20, SMCp22, and SMCp24, encoding still-cryptic compounds, had partially or totally downregulated their genes in the mutant, suggesting a regulatory role for ClaR wider than previously reported. In addition, the amfR gene was downregulated, and consequently, the mutant did not produce aerial mycelium. Expression levels of about 100 genes in the genome were partially up- or downregulated in the ΔclaR mutant, many of them related to the upregulation of the sigma factor-encoding rpoE gene.
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