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

McKenzie, Nancy; Nodwell, Justin R.

doi:10.1128/jb.00305-07

Cited by 90 publications

(70 citation statements)

References 53 publications

(48 reference statements)

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“…In addition to the aforementioned TCS AfsQ1/Q2, the involvement of a number of global or pleiotropic regulators has been described, including AdpA (a global regulator of both antibiotic biosynthesis and morphological differentiation) (19), AtrA (a TetR-family transcriptional activator) (20), DasR (a GntR-family regulator) (21), DraR and AbsA2 (the two-component response regulators) (22,23), and AbsC (a MarR-family regulator) (24), among others. These data clearly demonstrated the complexity of transcriptional regulation of actII-ORF4 expression.…”

Section: Discussionmentioning

confidence: 99%

Direct Involvement of the Master Nitrogen Metabolism Regulator GlnR in Antibiotic Biosynthesis in Streptomyces

Zhu

Zheng

et al. 2016

Journal of Biological Chemistry

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Edited by Joel GottesfeldGlnR, an OmpR-like orphan two-component system response regulator, is a master regulator of nitrogen metabolism in the genus Streptomyces. In this work, evidence that GlnR is also directly involved in the regulation of antibiotic biosynthesis is provided. In the model strain Streptomyces coelicolor M145, an in-frame deletion of glnR resulted in markedly increased actinorhodin (ACT) production but reduced undecylprodigiosin (RED) biosynthesis when exposed to R2YE culture medium. Transcriptional analysis coupled with DNA binding studies revealed that GlnR represses ACT but activates RED production directly via the pathway-specific activator genes actII-ORF4 and redZ, respectively. The precise GlnR-binding sites upstream of these two target genes were defined. In addition, the direct involvement of GlnR in antibiotic biosynthesis was further identified in Streptomyces avermitilis, which produces the important anthelmintic agent avermectin. We found that S. avermitilis GlnR (GlnRsav) could stimulate avermectin but repress oligomycin production directly through the respective pathway-specific activator genes, aveR and olmRI/RII. To the best of our knowledge, this report describes the first experimental evidence demonstrating that GlnR regulates antibiotic biosynthesis directly through pathway-specific regulators in Streptomyces. Our results suggest that GlnR-mediated regulation of antibiotic biosynthesis is likely to be universal in streptomycetes. These findings also indicate that GlnR is not only a master nitrogen regulator but also an important controller of secondary metabolism, which may help to balance nitrogen metabolism and antibiotic biosynthesis in streptomycetes.

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Section: Discussionmentioning

confidence: 99%

Direct Involvement of the Master Nitrogen Metabolism Regulator GlnR in Antibiotic Biosynthesis in Streptomyces

Zhu

Zheng

et al. 2016

Journal of Biological Chemistry

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“…Curiously, the nearly identical vegetative growth kinetics of the S. coelicolor rnc null mutant and the wild-type strain in liquid culture raise questions about the significance of rRNA processing by RNase III in S. coelicolor. It is possible that RNase III is one of many cooperative proteins that regulate antibiotic production (6,14,16). For instance, RNase III could catalyze a hydrolysis reaction that inactivates an mRNA en- FIG.…”

mentioning

confidence: 99%

The Gene Encoding RNase III in Streptomyces coelicolor Is Transcribed during Exponential Phase and Is Required for Antibiotic Production and for Proper Sporulation

Sello

Buttner

2008

J Bacteriol

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“…The cdaR gene product is known to positively regulate genes for the biosynthesis of the calcium-dependent antibiotic (CDA), and its activity might be modulated by phosphorylation (26). In addition, CdaR expression was shown to be repressed by AbsA2 and activated by ppGpp (24,29). This might provide indications for the study of the regulation of Srm22 expression.…”

Section: Discussionmentioning

confidence: 97%

Regulation of the Biosynthesis of the Macrolide Antibiotic Spiramycin in Streptomyces ambofaciens

et al. 2010

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Streptomyces ambofaciens synthesizes the macrolide antibiotic spiramycin. The biosynthetic gene cluster for spiramycin has been characterized for S. ambofaciens. In addition to the regulatory gene srmR (srm22), previously identified (M. Geistlich et al., Mol. Microbiol. 6:2019-2029, 1992), three putative regulatory genes had been identified by sequence analysis. Gene expression analysis and gene inactivation experiments showed that only one of these three genes, srm40, plays a major role in the regulation of spiramycin biosynthesis. The disruption of srm22 or srm40 eliminated spiramycin production while their overexpression increased spiramycin production. Expression analysis was performed by reverse transcription-PCR (RT-PCR) for all the genes of the cluster in the wild-type strain and in the srm22 (srmR) and srm40 deletion mutants. The results from the expression analysis, together with the ones from the complementation experiments, indicated that Srm22 is required for srm40 expression, Srm40 being a pathway-specific activator that controls most, if not all, of the spiramycin biosynthetic genes.Streptomyces species are Gram-positive, soil-inhabiting, filamentous bacteria that undergo a complex process of morphological differentiation and produce a great variety of secondary metabolites, including antibiotics with important applications in human medicine and in agriculture. These secondary metabolites are synthesized by complex pathways that utilize primary metabolites as building blocks. The genes required for

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Phosphorylated AbsA2 Negatively Regulates Antibiotic Production inStreptomyces coelicolorthrough Interactions with Pathway-Specific Regulatory Gene Promoters

Cited by 90 publications

References 53 publications

Direct Involvement of the Master Nitrogen Metabolism Regulator GlnR in Antibiotic Biosynthesis in Streptomyces

Direct Involvement of the Master Nitrogen Metabolism Regulator GlnR in Antibiotic Biosynthesis in Streptomyces

The Gene Encoding RNase III in Streptomyces coelicolor Is Transcribed during Exponential Phase and Is Required for Antibiotic Production and for Proper Sporulation

Regulation of the Biosynthesis of the Macrolide Antibiotic Spiramycin in Streptomyces ambofaciens

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