RS07910/07915 TCS multipath regulates clavulanic acid metabolic pathways in Streptomyces clavuligerus F613-1
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ABSTRACT:
PROVIDER: PRJNA488466 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7767280.fastq.gz | Fastqsanger.gz | |||
| SRR7767279.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:Streptomyces clavuligerus F613-1 produces a clinically important β-lactamase inhibitor, clavulanic acid (CA). The biosynthesis pathway of CA has been basically elucidated, however, the global regulation of CA biosynthesis remains unclear. In order to further elucidate the regulatory mechanism of clavulanic acid synthesis, TCS RS07910/07915 which is next to the CA biosynthetic gene cluster was deleted in Streptomyces clavuligerus. F613-1. Deletion of RS07910/07915 results in decreased the production of CA, but the phenotype was not affected. Both the transcriptome and ChIP-seq data revealed that the TCS RS07910/07915 mainly regulate genes involved in primary metabolism (such as fatty acid degradation, glyceraldehyde 3-phosphate (G3P) metabolism, arginine biosynthesis) and CA biosynthesis. EMSA assays revealed that RS07915 could bind to the promoter fragments of argG, argC, oat1, oat2, ceaS1 and claR in vitro, indicating that RS07915 could direct regulate the biosynthesis genes of arginine and CA. This study indicated that RS07910/07915 is a pleiotropy regulatory TCS, RS07910/07915 could directly affect the biosynthesis of CA, and indirectly affect CA production through affecting primary metabolism of arginine and G3P (precursors of CA).
2018-08-30 | GSE119208 | GEO
Project description:Clavulanic acid is a clinically-important secondary metabolite used in treatment of infectious diseases. We aimed to decipher complex regulatory mechanisms acting in clavulanic acid biosynthesis through the analysis of transcriptome- and proteome-wide alterations in an industrial clavulanic acid overproducer Streptomyces clavuligerus, namely DEPA and its wild-type counterpart NRRL3585.
2022-11-02 | PXD032272 | Pride
Project description:To investigate the function of organic nitrogen on clavulanic acid biosynthesis in Streptomyces clavuligerus, we established F613-1 strain cells cultured in MH fermentation medium and ML fermentation medium. We then performed gene expression profiling analysis using data obtained from RNA-seq of 2 different medium at three time points.
2022-08-25 | GSE211765 | GEO
Project description:To increase production of the important pharmaceutical compounds, both mutagenesis approaches and rational engineering have been extensively applied. Mutagenesis approaches are most popular in industry, but their effects have not yet been studied very well. Here, we used microarrays to compare the transcriptomes of the S. clavuligerus wild type (ATCC 27064) strain and the DS48802 clavulanic acid high-producer strain, which has been obtained by classical strain improvement (mutagenesis). Streptomyces clavuligerus strains were grown in shake flasks. RNA was extracted after 70h and hybridized to microarrays.
2010-11-10 | E-GEOD-24033 | biostudies-arrayexpress
Project description:To increase production of the important pharmaceutical compounds, both mutagenesis approaches and rational engineering have been extensively applied. Mutagenesis approaches are most popular in industry, but their effects have not yet been studied very well. Here, we used microarrays to compare the transcriptomes of the S. clavuligerus wild type (ATCC 27064) strain and the DS48802 clavulanic acid high-producer strain, which has been obtained by classical strain improvement (mutagenesis).
2010-11-10 | GSE24033 | GEO
Project description:<p>Clavulanic acid (CA) is the preferred clinical drug for the treatment of infections by β-lactam antibiotic-resistant bacteria. CA is produced by <em>Streptomyces clavuligerus</em>, and although there have been many reports on the effects of carbon and nitrogen sources on CA production, the mechanisms involved remain unclear. In this study, we found that CA accumulation in <em>S. clavuligerus</em> F613-1 was increased significantly in MH medium, which is rich in organic nitrogen, compared with that in ML medium, which contains half the amount of organic nitrogen present in MH medium. Transcriptome analysis revealed that genes involved in CA biosynthesis, such as <em>ceas1</em>, <em>ceas2</em>, <em>bls1</em>, <em>bls2</em>, <em>cas2</em>, <em>pah2</em>, <em>gcaS</em>, and <em>cad</em>, and arginine biosynthesis, such as <em>argB</em>, <em>argC</em>, <em>argD</em>, <em>argG</em>, <em>argH</em>, <em>argJ</em>, and <em>argR</em>, were upregulated under rich organic nitrogen. Metabolome data revealed notable differences between cultures of F613-1 grown in MH and ML media with regard to levels of key intracellular metabolites, most of which are involved in arginine metabolic pathways, including arginine, glutamine, and glutamic acid. Additionally, supplementation of ML medium with arginine, glutamine, or glutamic acid resulted in increased CA production by <em>S. clavuligerus</em> F613-1. Our results indicate that rich organic nitrogen mainly affects CA biosynthesis by increasing the levels of amino acids associated with the arginine metabolic pathway and activating the expression of the CA biosynthetic gene cluster. These findings provide important insights for improving medium optimization and engineering of <em>S. clavuligerus</em> F613-1 for high-yield production of CA.</p>
2022-12-08 | MTBLS5744 | MetaboLights
Project description:Effect of organic nitrogen on gene expression of clavulanic acid biosynthesis in Streptomyces clavuligerus F613-1
| PRJNA872036 | ENA
Project description:Streptomyces clavuligerus F613-1 produces a clinically important β-lactamase inhibitor, clavulanic acid (CA). Although the biosynthesis pathway of CA has essentially been elucidated, the global regulatory mechanisms of CA biosynthesis remain unclear. The paired genes cagS and cagR, which are annotated, respectively, as orf22 and orf23 in S. clavuligerus ATCC 27064, encode a bacterial two-component regulatory system (TCS) and were found next to the CA biosynthetic gene cluster of S. clavuligerus F613-1. To further elucidate the regulatory mechanism of CA biosynthesis, the CagRS TCS was deleted from S. clavuligerus F613-1. Deletion of cagRS resulted in decreased production of CA, but the strain phenotype was not otherwise affected. Both transcriptome and ChIP-seq data revealed that, in addition to CA biosynthesis, the CagRS TCS mainly regulates genes involved in primary metabolism, such as glyceraldehyde 3-phosphate (G3P) metabolism and arginine biosynthesis. Notably, both G3P and arginine are precursors of CA. Electrophoretic mobility shift assays demonstrated that the response regulator CagR could bind to the intergenic regions of argG, argC, oat1, oat2, ceaS1, and claR in vitro, suggesting that CagR can directly regulate genes involved in arginine and CA biosynthesis. This study indicated that CagRS is a pleiotropic regulator that can directly affect the biosynthesis of CA and indirectly affect CA production by regulating the metabolism of arginine and G3P. Our findings provide new insights into the regulation of CA biosynthetic pathways and provide an innovative approach for future metabolic engineering efforts for CA production in S. clavuligerus.
| S-EPMC6382702 | biostudies-literature
Project description:The objective was to analyze the differential expression between the control strain and S. clavuligerus::pimM. Experiment type Expression profiling by array
2019-03-01 | GSE87092 | GEO
Project description:Clavulanic acid (CA) is the preferred clinical drug for the treatment of infections by β-lactam antibiotic-resistant bacteria. CA is produced by Streptomyces clavuligerus, and although there have been many reports on the effects of carbon and nitrogen sources on CA production, the mechanisms involved remain unclear. In this study, we found that CA accumulation in S. clavuligerus F613-1 was increased significantly in MH medium, which is rich in organic nitrogen, compared with that in ML medium, which contains half the amount of organic nitrogen present in MH medium. Transcriptome analysis revealed that genes involved in CA biosynthesis, such as ceas1, ceas2, bls1, bls2, cas2, pah2, gcaS, and cad, and arginine biosynthesis, such as argB, argC, argD, argG, argH, argJ, and argR, were upregulated under rich organic nitrogen. Metabolome data revealed notable differences between cultures of F613-1 grown in MH and ML media with regard to levels of key intracellular metabolites, most of which are involved in arginine metabolic pathways, including arginine, glutamine, and glutamic acid. Additionally, supplementation of ML medium with arginine, glutamine, or glutamic acid resulted in increased CA production by S. clavuligerus F613-1. Our results indicate that rich organic nitrogen mainly affects CA biosynthesis by increasing the levels of amino acids associated with the arginine metabolic pathway and activating the expression of the CA biosynthetic gene cluster. These findings provide important insights for improving medium optimization and engineering of S. clavuligerus F613-1 for high-yield production of CA. IMPORTANCE The bacterium Streptomyces clavuligerus is used for the industrial production of the broad-spectrum β-lactamase inhibitor clavulanic acid (CA). However, much remains unknown about the factors which affect CA yields. We investigated the effects of different levels of organic nitrogen on CA production. Our analyses indicate that higher organic nitrogen levels were associated with increased CA yields and increased levels of arginine biosynthesis. Further analyses supported the relationship between arginine metabolism and CA production and demonstrated that increasing the levels of arginine or associated amino acids could boost CA yields. These findings suggest approaches for improving the production of this clinically important antibiotic.
| S-EPMC9927107 | biostudies-literature