The dynamic architecture of the metabolic switch in Streptomyces coelicolor

@article{Nieselt2009TheDA,
  title={The dynamic architecture of the metabolic switch in Streptomyces coelicolor},
  author={K. Nieselt and F. Battke and A. Herbig and P. Bruheim and A. Wentzel and {\O}yvind M. Jakobsen and H. Sletta and Mohammad T. Alam and M. E. Merlo and Jonathan D. Moore and Walid A. M. Omara and E. Morrissey and Miguel A Juarez-Hermosillo and A. Rodríguez-García and M. Nentwich and L. Thomas and M. Iqbal and Roxane Legaie and W. Gaze and G. Challis and R. Jansen and L. Dijkhuizen and D. Rand and D. Wild and M. Bonin and J. Reuther and W. Wohlleben and Margaret C. M. Smith and N. Burroughs and J. Mart{\'i}n and D. Hodgson and E. Takano and R. Breitling and T. Ellingsen and E. Wellington},
  journal={BMC Genomics},
  year={2009},
  volume={11},
  pages={10 - 10}
}
BackgroundDuring the lifetime of a fermenter culture, the soil bacterium S. coelicolor undergoes a major metabolic switch from exponential growth to antibiotic production. We have studied gene expression patterns during this switch, using a specifically designed Affymetrix genechip and a high-resolution time-series of fermenter-grown samples.ResultsSurprisingly, we find that the metabolic switch actually consists of multiple finely orchestrated switching events. Strongly coherent clusters of… Expand
Metabolic modeling and analysis of the metabolic switch in Streptomyces coelicolor
TLDR
This work reconstructed the stoichiometric matrix of S. coelicolor, including the major antibiotic biosynthesis pathways, and performed flux balance analysis to predict flux changes that occur when the cell switches from biomass to antibiotic production. Expand
Metabolic Switches and Adaptations Deduced from the Proteomes of Streptomyces coelicolor Wild Type and phoP Mutant Grown in Batch Culture*
TLDR
There is a succession of switches that coordinately induce the production of enzymes for five different secondary metabolite biosynthesis pathways over the course of the batch cultures, and several putatively compensatory metabolic and regulatory pathways for phosphate scavenging were detected. Expand
Temporal Dynamics of the Saccharopolyspora erythraea Phosphoproteome*
TLDR
Evidence of dynamic protein phosphorylation events across the developmental cycle of actinomycetes is provided, supporting the hypothesis that ribosome subpopulations differentially regulate translation before and after the metabolic switch. Expand
Saccharopolyspora erythraea’s genome is organised in high-order transcriptional regions mediated by targeted degradation at the metabolic switch
TLDR
The metabolic switch is a sophisticated mechanism of transcriptional regulation capable of resetting and re-synchronizing gene expression programs at extraordinary speed and scale and revealed unanticipated transcriptional complexity. Expand
The expression of the acarbose biosynthesis gene cluster in Actinoplanes sp. SE50/110 is dependent on the growth phase
TLDR
It is demonstrated, that a genome wide transcriptome and proteome analysis in a high temporal resolution is well suited to study the acarbose biosynthesis and the transcriptional and post-transcriptional regulation thereof. Expand
Genome-scale Model Constrained by Proteomics Reveals Metabolic Rearrangements in the Heterologous Host Streptomyces coelicolor
TLDR
This study compares M1152 to its ancestor M145, thereby connecting observed phenotypic differences to changes on transcription and translation, and suggests that precursors supply is not limiting secondary metabolism, informing that alternative strategies will be beneficial for further development of S. coelicolor. Expand
Enzyme-Constrained Models and Omics Analysis of Streptomyces coelicolor Reveal Metabolic Changes that Enhance Heterologous Production
TLDR
It is found that this strain suffers from oxidative stress, possibly caused by increased oxidative metabolism, and precursor availability is likely not limiting polyketide production, implying that other strategies could be beneficial for further development of S. coelicolor for heterologous production of novel compounds. Expand
Dynamical modelling of secondary metabolism and metabolic switches in Streptomyces xiamenensis 318
TLDR
It is shown that the enzyme-catalysed process may improve the metabolic stability of the cells and increase the metabolic fitness of the organism via stabilizing the underlying metabolic network. Expand
Metabolomic analysis of a synthetic metabolic switch in Streptomyces coelicolor A3(2)
TLDR
It is shown that the overexpression of an antisense non‐coding RNA targeting glutamine synthetase I results in a major reorganization of the metabolism of Streptomyces coelicolor, the model species of antibiotic‐producing bacteria. Expand
Enzyme-constrained models and omics analysis of Streptomyces coelicolor reveal metabolic changes that enhance heterologous production
TLDR
It is found that this strain suffers from oxidative stress, possibly caused by increased oxidative metabolism, and precursor availability is likely not limiting polyketide production, implying that other strategies could be beneficial for further development of S. coelicolor for heterologous production of novel compounds. Expand
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TLDR
Although the need forppGpp in triggering antibiotic production remains equivocal, ppGpp synthesis atone does not appear to be sufficient to initiate secondary metabolism in S. coelicolor A3(2), and the effect of provoking the stringent response on antibiotic production in exponentially growing cultures was assessed. Expand
The global role of ppGpp synthesis in morphological differentiation and antibiotic production in Streptomyces coelicolor A3(2)
TLDR
In S. coelicolor, ppGpp synthesis influences the expression of several genomic elements that are particularly characteristic of streptomycete biology, notably antibiotic gene clusters, conservons, and morphogenetic proteins. Expand
Global analysis of growth phase responsive gene expression and regulation of antibiotic biosynthetic pathways in Streptomyces coelicolor using DNA microarrays.
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A knowledge-based algorithm that correlates temporal changes in expression with chromosomal position identified groups of contiguous genes expressed at discrete stages of morphological development, inferred the boundaries of known antibiotic synthesis gene loci, and revealed novel physical clusters of coordinately regulated genes. Expand
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TLDR
The bldA molecular phenotype revealed by the "dualomic" approach has shown that only about 2% of the genome is affected; but this includes many previously unknown effects at a variety of different levels, including post-translational changes in proteins and global cellular physiology. Expand
Genome-wide transcriptome analysis reveals that a pleiotropic antibiotic regulator, AfsS, modulates nutritional stress response in Streptomyces coelicolor A3(2)
TLDR
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Transcriptional regulation of the redD transcriptional activator gene accounts for growth‐phase‐dependent production of the antibiotic undecylprodigiosin in Streptomyces coelicolor A3(2)
TLDR
Transcription of redD, the activator gene required for production of the red‐pigmented antibiotic undecylprodigiosin by Streptomyces coelicolor A3(2), showed a dramatic increase during the transition from exponential to stationary phase, which appeared to be mediated entirely through the redD promoter, which shows limited similarity to the consensus sequence for the major class of eubacterial promoters. Expand
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TLDR
Surprisingly, some genes show high similarity to primary metabolite genes not commonly identified in any antibiotic biosynthesis cluster, and are shown to be expressed in S. coelicolor at transition phase. Expand
Genome‐wide transcriptomic and proteomic analysis of the primary response to phosphate limitation in Streptomyces coelicolor M145 and in a ΔphoP mutant
TLDR
The primary response to phosphate limitation involves upregulation of genes encoding scavenging enzymes needed to obtain phosphate from different phosphorylated organic compounds and overexpression of the high‐affinity phosphate transport system pstSCAB. Expand
Nitrogen Metabolism in Streptomyces coelicolor: Transcriptional and Post-Translational Regulation
Glutamine synthetases (GS) are key enzymes of nitrogen metabolism. Most bacteria contain only one type of GS enzyme encoded by glnA. Streptomyces coelicolor, the model organism for Gram-positiveExpand
Production of actinorhodin-related "blue pigments" by Streptomyces coelicolor A3(2)
TLDR
Analysis of act mutants of S. coelicolor A3(2) confirmed that both pigments are derived from the act biosynthetic pathway, and synthesis of gamma-actinorhodin from actin orhodin is coupled to its export from the cell. Expand
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