Phosphorylated AbsA2 Negatively Regulates Antibiotic Production in Streptomyces coelicolor through Interactions with Pathway-Specific Regulatory Gene Promoters

@article{McKenzie2007PhosphorylatedAN,
  title={Phosphorylated AbsA2 Negatively Regulates Antibiotic Production in Streptomyces coelicolor through Interactions with Pathway-Specific Regulatory Gene Promoters},
  author={Nancy L McKenzie and Justin Rea Nodwell},
  journal={Journal of Bacteriology},
  year={2007},
  volume={189},
  pages={5284 - 5292}
}
ABSTRACT The AbsA two-component signal transduction system, comprised of the sensor kinase AbsA1 and the response regulator AbsA2, acts as a negative regulator of antibiotic production in Streptomyces coelicolor, for which the phosphorylated form of AbsA2 (AbsA2∼P) is the agent of repression. In this study, we used chromatin immunoprecipitation to show that AbsA2 binds the promoter regions of actII-ORF4, cdaR, and redZ, which encode pathway-specific activators for actinorhodin, calcium… Expand
Genome-wide analysis of the role of the antibiotic biosynthesis regulator AbsA2 in Streptomyces coelicolor A3(2)
TLDR
The analysis of a ΔabsA2 deletion strain, which exhibits the classic precocious antibiotic hyper-production phenotype, and its complementation by an N-terminal triple-FLAG-tagged version of AbsA2 sheds light on the complex mechanism of regulation of antibiotic biosynthesis in Streptomyces coelicolor. Expand
Genome-wide analysis of the role of the antibiotic biosynthesis regulator AbsA2 in Streptomyces coelicolor A3(2)
TLDR
The analysis of a ΔabsA2 deletion strain, which exhibits the classic precocious antibiotic hyper-production phenotype, and its complementation by an N-terminal triple-FLAG-tagged version of AbsA2 sheds light on the complex mechanism of regulation of antibiotic biosynthesis in Streptomyces coelicolor. Expand
Identification of different promoters in the absA1–absA2 two-component system, a negative regulator of antibiotic production in Streptomyces coelicolor
TLDR
It is shown by different technical approaches that the absA1–absA2 operon is transcribed from at least two promoters, the first producing a read-through transcript that includes both abs a1 and absA2 genes and the second including only the abs a2 gene. Expand
Deciphering the Regulon of Streptomyces coelicolor AbrC3, a Positive Response Regulator of Antibiotic Production
TLDR
It is demonstrated that deletion of the RR-encoding gene, abrC3 (SCO4596), results in a dramatic decrease in actinorhodin (ACT) and undecylprodiginine (RED) production and delays morphological development and may contribute to the rational design of new hyperproducer host strains through genetic manipulation of such systems. Expand
Pleiotropic regulatory genes bldA, adpA and absB are implicated in production of phosphoglycolipid antibiotic moenomycin
TLDR
This work highlights an underappreciated strategy for secondary metabolism regulation, in which the interaction between structural genes and pleiotropic regulators is not mediated by CSRs, and might be relevant for a growing number of CSR-free gene clusters unearthed during actinomycete genome mining. Expand
Repression of Antibiotic Production and Sporulation in Streptomyces coelicolor by Overexpression of a TetR Family Transcriptional Regulator
TLDR
The direct and functional interaction of SCO3201 with the promoter region of scbA, a gene under the positive control of the TetR-like regulator, ScbR, was indeed demonstrated by in vitro as well as in vivo approaches. Expand
Deciphering the Regulon of the Streptomyces Coelicolor Abrc3, a Positive Response 1 Regulator of Antibiotic Production. 2
18 The atypical two-component system (TCS) AbrC1/2/3 (encoded respectively by 19 SCO4598/4597/4596), comprising two histidine kinases (HKs) and a response regulator 20 (RR), is crucial for antibioticExpand
Direct Involvement of the Master Nitrogen Metabolism Regulator GlnR in Antibiotic Biosynthesis in Streptomyces.
TLDR
The first experimental evidence demonstrating that GlnR regulates antibiotic biosynthesis directly through pathway-specific regulators in Streptomyces is described, suggesting thatglnR-mediated regulation of antibiotic biosynthetic is likely to be universal in streptomycetes. Expand
Crp Is a Global Regulator of Antibiotic Production in Streptomyces
TLDR
It is demonstrated that Crp is a key regulator of secondary metabolism and antibiotic production in S. coelicolor and show that it may additionally coordinate precursor flux from primary to secondary metabolism. Expand
Study on a two-component signal transduction system RimA1A2 that negatively regulates oxytetracycline biosynthesis in Streptomyces rimosus M4018
TLDR
Using RT-PCR analysis, it is demonstrated that rimA1 encodes response regulator (RR) and rimA2 encoding histidine kinase (HK) from S. rimosus that are co-transcribed as a single-polycistronic mRNA, supporting the hypothesis that RimA1A2 has a negative regulatory role in OTC biosynthesis via global regulation. Expand
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Transcriptional Regulation of Streptomyces coelicolorPathway-Specific Antibiotic Regulators by the absA andabsB Loci
TLDR
The results establish that the abs genes affect production of antibiotics through regulation of expression of the antibiotic-specific regulatory genes in S. coelicolor through regulating transcript abundance from the biosynthetic and regulatory genes specific for each antibiotic. Expand
Biochemical Activities of the absA Two-Component System of Streptomyces coelicolor
TLDR
The results support a model in which the phosphorylation state of AbsA2 is determined by the balance of the kinase and phosphatase activities of absA1 and where AbsA 2 approximately P represses antibiotic biosynthetic genes either directly or indirectly. Expand
Genetic and transcriptional analysis of absA, an antibiotic gene cluster‐linked two‐component system that regulates multiple antibiotics in Streptomyces coelicolor
TLDR
A genetic analysis shows that the phosphorylated form of the AbsA2 response regulator (phospho‐AbsA2), generated by the cognate AbsA1 sensor histidine kinase, is required for normal growth phase regulation of antibiotic synthesis. Expand
Regulation of the Streptomyces coelicolor Calcium-Dependent Antibiotic by absA, Encoding a Cluster-Linked Two-Component System
TLDR
This paper has identified numerous transcriptional start sites within the CDA cluster and shown that the original antibiotic-negative mutants used to identify absA exhibit a stronger negative regulation of promoters upstream of the proposed CDA biosynthetic genes than of promoters in the clusters responsible for production of actinorhodin and undecylprodigiosin. Expand
Global negative regulation of Streptomyces coelicolor antibiotic synthesis mediated by an absA-encoded putative signal transduction system
TLDR
It is proposed that the absA locus encodes a signal transduction mechanism that negatively regulates synthesis of the multiple antibiotics produced by S. coelicolor. Expand
A Streptomyces coelicolor Antibiotic Regulatory Gene, absB, Encodes an RNase III Homolog
TLDR
This study isolated absB-complementing DNA and shows that it encodes the S. coelicolor homolog of RNase III (rnc), indicating that the absB mutant global defect in antibiotic synthesis is due to a deficiency inRNase III. Expand
Transcriptional activation of the pathway‐specific regulator of the actinorhodin biosynthetic genes in Streptomyces coelicolor
TLDR
Findings provide further evidence that the path leading to the expression of pathway‐specific activators of antibiotic biosynthesis genes in disparate Streptomyces may share evolutionarily conserved components in at least some cases, and suggests that the regulation of streptomycin production, which serves an important paradigm, may be more complex than represented by current models. Expand
Characterization of the Pathway-Specific Positive Transcriptional Regulator for Actinorhodin Biosynthesis inStreptomyces coelicolor A3(2) as a DNA-Binding Protein
TLDR
Although both gene products (wild-type and mutant ActII-ORF4) showed DNA-binding activity, only the wild-type gene was capable of activating transcription of the act genes; thus, two basic functions can be differentiated within the regulatory protein. Expand
Bacillus subtilis PhoP binds to the phoB tandem promoter exclusively within the phosphate starvation-inducible promoter
TLDR
Experiments indicate that PhoP, a response regulator, is furthest downstream of the known regulators in the signaling pathway that regulates Pho regulon genes, and suggest that activation of phoB is via direct interaction betweenPhoP and the pho B promoter. Expand
A bacterial hormone (the SCB1) directly controls the expression of a pathway‐specific regulatory gene in the cryptic type I polyketide biosynthetic gene cluster of Streptomyces coelicolor
TLDR
This is the first report with comprehensive in vivo and in vitro data to show that a γ‐butyrolactone‐binding protein directly regulates a secondary metabolite pathway‐specific regulatory gene in Streptomyces. Expand
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