Transcriptome analysis of wild type and erythromycin-producing strain of S. erythraea
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ABSTRACT:
ORGANISM(S): Saccharopolyspora erythraea
PROVIDER: GSE65007 | GEO | 2016/06/22
SECONDARY ACCESSION(S): PRJNA272711
REPOSITORIES: GEO
Similar Datasets
Project description:Erythromycin is a medically important antibiotic, biosynthesized by the actinomycete Saccharopolyspora erythraea. We used transcriptomic approach to compare whole genome expression in erythromycin high-producing strain, compared to the wild type S. erythraea strain in four stages of fermentation. 2 strains (3 individual fermentations each), 4 time points --> 24 samples (2 exluded from anaysis, 22 remaining); one color design
2016-06-22 | E-GEOD-65007 | biostudies-arrayexpress
Project description:In this study we have used the rifampicin selection as a tool to genetically improve the erythromycin producer Saccharopolyspora erythraea. Two rifampicin-resistant (rif) mutants, rif1 and rif6, have been characterized in more detail. With respect to the parental strain NRRL2338, rif1 (harboring the missense S444F) exhibited higher respiratory performance and final erythromycin yields; in contrast, rif6 (harboring the missense Q426R) was slow-growing, developmental-defective and severely impaired in erythromycin production. The results of genome-wide analysis of expression profiles using DNA micro-arrays demonstrated that these mutations deeply changed the transcriptional profile of S. erythraea with marked regional distribution. Keywords: mutants versus wild type comparison in a time course experiment
2009-04-12 | GSE12017 | GEO
Project description:In this study we have used the rifampicin selection as a tool to genetically improve the erythromycin producer Saccharopolyspora erythraea. Two rifampicin-resistant (rif) mutants, rif1 and rif6, have been characterized in more detail. With respect to the parental strain NRRL2338, rif1 (harboring the missense S444F) exhibited higher respiratory performance and final erythromycin yields; in contrast, rif6 (harboring the missense Q426R) was slow-growing, developmental-defective and severely impaired in erythromycin production. The results of genome-wide analysis of expression profiles using DNA micro-arrays demonstrated that these mutations deeply changed the transcriptional profile of S. erythraea with marked regional distribution. Keywords: mutants versus wild type comparison in a time course experiment Total of 12 Samples
2009-04-12 | E-GEOD-12017 | biostudies-arrayexpress
Project description:Abstract: Transcript levels in production cultures of wildtype and classically improved strains of the actinomycete bacteria Saccharopolyspora erythraea and Streptomyces fradiae were monitored using microarrays of the sequenced actinomycete S. coelicolor. Sac. erythraea and S. fradiae synthesize the polyketide antibiotics erythromycin and tylosin, respectively, and the classically improved strains contain unknown overproduction mutations. The Sac. erythraea overproducer was found to express the entire 56-kb erythromycin gene cluster several days longer than the wildtype strain. In contrast, the S. fradiae wildtype and overproducer strains expressed the 85-kb tylosin biosynthetic gene cluster similarly, while they expressed several tens of other S. fradiae genes and S. coelicolor homologs differently, including the acyl-CoA dehydrogenase gene aco and the S. coelicolor isobutyryl-CoA mutase homolog icmA. These observations indicated that overproduction mechanisms in classically improved strains can affect both the timing and rate of antibiotic synthesis, and alter the regulation of antibiotic biosynthetic enzymes and enzymes involved in precursor metabolism. This SuperSeries is composed of the SubSeries listed below.
2006-03-08 | GSE4395 | GEO
Project description:Abstract: Transcript levels in production cultures of wildtype and classically improved strains of the actinomycete bacteria Saccharopolyspora erythraea and Streptomyces fradiae were monitored using microarrays of the sequenced actinomycete S. coelicolor. Sac. erythraea and S. fradiae synthesize the polyketide antibiotics erythromycin and tylosin, respectively, and the classically improved strains contain unknown overproduction mutations. The Sac. erythraea overproducer was found to express the entire 56-kb erythromycin gene cluster several days longer than the wildtype strain. In contrast, the S. fradiae wildtype and overproducer strains expressed the 85-kb tylosin biosynthetic gene cluster similarly, while they expressed several tens of other S. fradiae genes and S. coelicolor homologs differently, including the acyl-CoA dehydrogenase gene aco and the S. coelicolor isobutyryl-CoA mutase homolog icmA. These observations indicated that overproduction mechanisms in classically improved strains can affect both the timing and rate of antibiotic synthesis, and alter the regulation of antibiotic biosynthetic enzymes and enzymes involved in precursor metabolism. This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2006-03-08 | E-GEOD-4395 | biostudies-arrayexpress
Project description:We report the high-throughput profiling of saccharopolyspora erythraea including a industrial strain HL3168 E3 and a wild-type strain NRRL23338. The aim was to evaluate the difference in expression of sRNA predicted in silico related to secondary metabolites in Saccharopolyspora erythraea.
2013-07-16 | GSE48887 | GEO
Project description:Saccharopolyspora erythraea is used for industrial-scale production of erythromycin. To explore the physiological role of co-factors in regulation of primary and secondary metabolism of S. erythraea, we initially overexpressed the endogenous F1-ATPase in an erythromycin high-producing strain, E3. The engineered strain is named EA. The F1-ATPase expression resulted in a lower [ATP]/[ADP] ratio, which was accompanied by a dramatic increased production of a reddish pigment and a decreased erythromycin production. Transcriptional analysis revealed that the intracellular [ATP]/[ADP] ratio appeared to exert a global regulation on the metabolism of S.erythraea, and the lower [ATP]/[ADP] ratio induced physiological changes to restore the energy balance, mainly via pathways that tend to produce ATP or NADH. The results also indicated a state of redox stress in the engineered strain, which was correlated to the alteration of electron transport at the branch of the terminal oxidases.
2020-02-26 | GSE134767 | GEO
Project description:We report the high-throughput profiling of saccharopolyspora erythraea including a industrial strain HL3168 E3 and a wild-type strain NRRL23338. The aim was to evaluate the difference in expression of sRNA predicted in silico related to secondary metabolites in Saccharopolyspora erythraea. Comparison of the gene expression difference in 2 Saccharopolyspora erythraea strains.
2013-07-16 | E-GEOD-48887 | biostudies-arrayexpress
Project description:Knowledge about effects of cofactor perturbation on cellular metabolism is scarce with respect to Saccharopolyspora erythraea. The water-forming NADH oxidase (NOX) from Streptococcus pneumonia was expressed in S.erythraea E3, an important industrial strain for erythromycin production, at three different levels to investigate effects of intracellular redox status on secondary metabolism. NOX expression reduced the intracellular [NADH]/[NAD+] ratios significantly, although with a strong constitutive promoter NOX function was limited due to the shortage of oxygen. We demonstrated the negative correlation between [NADH]/[NAD+] ratios and biosynthesis of erythromycin in S.erythraea, but a positive correlation between the redox ratios and pigment production as well. We furthermore completed next-generation RNA sequencing of E3 and two NOX-expression strains. The transcription results showed that transfer processes of carbohydrates, DNA and chemical groups were altered resulting in metabolic shifts to supply more NADH for NOX fully functioning. Additionally, redox status affected transcription of several genes by allosteric effects on their transcription initiation. Specifically, transcriptional analysis along with enzymatic assay suggested that redox status influenced biosynthesis of erythromycin indirectly by allosteric effects on biosynthesis of the secondary messenger, c-di-GMP. The present work provides a basis for future cofactor manipulation in S.erythraea for further improvement of erythromycin production.
2020-08-04 | GSE144067 | GEO
Project description:Information about molecular mechanisms underlying improvement of antibiotic-producing microorganisms with traditional mutation and screening approach is largely missing. This information is essential to develop rational approaches to strain improvement. In this study by using comparative genomic analysis we have identified all genetic changes that have occurred during development of an erythromycin overproducer, which was obtained by the traditional mutate-and-screen method. Compared with parental Saccharopolyspora erythraea NRRL 2338, a total of 117 deletion, 78 insertion and 12 transposition sites were found across the genome of the overproducer. Among them, 71 insertion/deletion sites mapped within coding sequences (CDSs) generating frame-shift mutations. Moreover, single nucleotide variations affecting a total of 144 CDSs were identified between the two genomes. Overall, variations affect a total of 227 proteins in the genome of the overproducer. The analysis of metabolic pathways demonstrated that a considerable number of mutations affect genes coding for key enzymes involved in central carbon and nitrogen metabolism, and biosynthesis of secondary metabolites, redirecting common precursors toward erythromycin biosynthesis. Interestingly, several mutations inactivate genes coding for proteins that play fundamental roles in basic transcription and translation machineries including the transcription anti-termination factor NusB and the transcription elongation factor Efp. These mutations, along with those affecting genes coding for pleiotropic or pathway-specific regulators, may affect global expression profile. Consistent transcriptomic data were obtained from a comparative analysis between NRRL 2338 and the erythromycin overproducer gene expression profiling performed with DNA microarray. Genomic data also indicated that the mutate-and-screen process might have been accelerated by mutations in DNA repair genes. Our findings, largely unanticipated, reveal new targets suitable for rationale improvement of antibiotic-producing strains. According to a rough estimate, actinomycetes, which are among the most abundant bacteria in soil, produce over 70% of naturally occurring antibiotics and other biologically active substances including anti-tumour agents and immunosuppressants. However, these microorganisms must often be genetically improved for higher production before they can be used in the industry. Strain improvement has traditionally relied on multiple rounds of random mutagenesis and screening. This method is essentially empirical, and notably time-consuming and expansive. Currently, the availability of molecular genetics tools and useful information about the biosynthetic pathways and genetic control for most of biologically active substances has opened the way for improving strains by rational engineering. These rational strain improvement strategies benefit of the support of genomic and post-genomic technologies. In this study by using comparative genomic analysis we have identified all genetic changes that have occurred during development of an erythromycin overproducer, which was obtained by the traditional mutate-and-screen method. Our findings, largely unanticipated, reveal new molecular targets suitable for rationale improvement of antibiotic-producing strains by recombinant technologies, and support the evidence that combining classical and recombinant strain improvement with a solid fermentation development program is the best way to improve production of biologically active substances. Erythromycin over-producing Strain at various time points
2012-05-23 | E-GEOD-30600 | biostudies-arrayexpress