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).
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.
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.
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.
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).
Project description:The objective was to analyze the differential expression between the control strain and S. clavuligerus::pimM. Experiment type Expression profiling by array
