ArticleMicrobial cell factories2009
Phenotypes and gene expression profiles of Saccharopolyspora erythraea rifampicin-resistant (rif) mutants affected in erythromycin production.
Article in Microbial cell factories, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 52 citations in OpenAlex.
- PhoP- and GlnR-mediated regulation of metK transcription and its impact upon S-adenosyl-methionine biosynthesis in Saccharopolyspora erythraea.Microbial cell factories · 2022Article
- Phosphate regulator PhoP directly and indirectly controls transcription of the erythromycin biosynthesis genes in Saccharopolyspora erythraea.Microbial cell factories · 2019Article
- The Application of Ribosome Engineering to Natural Product Discovery and Yield Improvement inAntibiotics (Basel, Switzerland) · 2019Review
- Characterization and engineering of the Lrp/AsnC family regulator SACE_5717 for erythromycin overproduction in Saccharopolyspora erythraea.Journal of industrial microbiology & biotechnology · 2019Article
- Rifampicin-Resistance Mutations in theFrontiers in microbiology · 2017Article
- Insights into microbial cryptic gene activation and strain improvement: principle, application and technical aspects.The Journal of antibiotics · 2017Review
- Engineering microbial hosts for production of bacterial natural products.Natural product reports · 2016Review
- Integrated omics approaches provide strategies for rapid erythromycin yield increase in Saccharopolyspora erythraea.Microbial cell factories · 2016Article
- Genetic manipulation of secondary metabolite biosynthesis for improved production in Streptomyces and other actinomycetes.Journal of industrial microbiology & biotechnology · 2016Review
- Article
- Testing the role of genetic background in parallel evolution using the comparative experimental evolution of antibiotic resistance.Molecular biology and evolution · 2014Article
- Suitable extracellular oxidoreduction potential inhibit rex regulation and effect central carbon and energy metabolism in Saccharopolyspora spinosa.Microbial cell factories · 2014Article
- Activating the expression of bacterial cryptic genes by rpoB mutations in RNA polymerase or by rare earth elements.Journal of industrial microbiology & biotechnology · 2014Review
- The respiratory chains of four strains of the alkaliphilic Bacillus clausii.FEBS open bio · 2014Article
- SACE_5599, a putative regulatory protein, is involved in morphological differentiation and erythromycin production in Saccharopolyspora erythraea.Microbial cell factories · 2013Article
- Genome Sequence of Saccharopolyspora erythraea D, a Hyperproducer of Erythromycin.Genome announcements · 2013Article
- Systems perspectives on erythromycin biosynthesis by comparative genomic and transcriptomic analyses of S. erythraea E3 and NRRL23338 strains.BMC genomics · 2013Article
- Activation and products of the cryptic secondary metabolite biosynthetic gene clusters by rifampin resistance (rpoB) mutations in actinomycetes.Journal of bacteriology · 2013Article
- Saccharopolyspora erythraea's genome is organised in high-order transcriptional regions mediated by targeted degradation at the metabolic switch.BMC genomics · 2013Article
- New strategies for drug discovery: activation of silent or weakly expressed microbial gene clusters.Applied microbiology and biotechnology · 2013Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThere is evidence from previous works that bacterial secondary metabolism may be stimulated by genetic manipulation of RNA polymerase (RNAP). In this study we have used rifampicin selection as a strategy to genetically improve the erythromycin producer Saccharopolyspora erythraea.
resultsSpontaneous rifampicin-resistant (rif) mutants were isolated from the parental strain NRRL2338 and two rif mutations mapping within rpoB, S444F and Q426R, were characterized. With respect to the parental strain, S444F mutants exhibited higher respiratory performance and up to four-fold higher final erythromycin yields; in contrast, Q426R mutants were slow-growing, developmental-defective and severely impaired in erythromycin production. DNA microarray analysis demonstrated that these rif mutations deeply changed the transcriptional profile of S. erythraea. The expression of genes coding for key enzymes of carbon (and energy) and nitrogen central metabolism was dramatically altered in turn affecting the flux of metabolites through erythromycin feeder pathways. In particular, the valine catabolic pathway that supplies propionyl-CoA for biosynthesis of the erythromycin precursor 6-deoxyerythronolide B was strongly up-regulated in the S444F mutants, while the expression of the biosynthetic gene cluster of erythromycin (ery) was not significantly affected. In contrast, the ery cluster was down-regulated (<2-fold) in the Q426R mutants. These strains also exhibited an impressive stimulation of the nitrogen regulon, which may contribute to lower erythromycin yields as erythromycin production was strongly inhibited by ammonium.
conclusionRifampicin selection is a simple and reliable tool to investigate novel links between primary and secondary metabolism and morphological differentiation in S. erythraea and to improve erythromycin production. At the same time genome-wide analysis of expression profiles using DNA microarrays allowed information to be gained about the mechanisms underlying the stimulatory/inhibitory effects of the rif mutations on erythromycin production.
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