Nitrogen Metabolism in &lt;i&gt;Streptomyces coelicolor&lt;/i&gt;: Transcriptional and Post-Translational Regulation

Reuther, Jens; Wohlleben, Wolfgang

doi:10.1159/000096469

Cited by 87 publications

(102 citation statements)

References 61 publications

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“…30 This motif has been updated by Sola-Landa et al 31 The binding site of the second regulator, GlnRII, is not well known. 32 PhoP binds the glnR promoter, the promoters of glnA and glnII and the promoter region of the amtB-glnK-glnD operon. No binding of PhoP to the glnRII promoter was found under identical experimental conditions, both in S. coelicolor and S. avermitilis; 4,8 however, Allenby et al 19 proposed, based on transcriptomic and ChIP-on-chip studies, that PhoP regulated also glnRII expression.…”

Section: Cross Regulation Of Nitrogen Metabolism and Phopmentioning

confidence: 99%

The master regulator PhoP coordinates phosphate and nitrogen metabolism, respiration, cell differentiation and antibiotic biosynthesis: comparison in Streptomyces coelicolor and Streptomyces avermitilis

2017

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Phosphate limitation is important for production of antibiotics and other secondary metabolites in Streptomyces. Phosphate control is mediated by the two-component system PhoR-PhoP. Following phosphate depletion, PhoP stimulates expression of genes involved in scavenging, transport and mobilization of phosphate, and represses the utilization of nitrogen sources. PhoP reduces expression of genes for aerobic respiration and activates nitrate respiration genes. PhoP activates genes for teichuronic acid formation and reduces expression of genes for phosphate-rich teichoic acid biosynthesis. In Streptomyces coelicolor, PhoP repressed several differentiation and pleiotropic regulatory genes, which affects development and indirectly antibiotic biosynthesis. A new bioinformatics analysis of the putative PhoP-binding sequences in Streptomyces avermitilis was made. Many sequences in S. avermitilis genome showed high weight values and were classified according to the available genetic information. These genes encode phosphate scavenging proteins, phosphate transporters and nitrogen metabolism genes. Among of the genes highlighted in the new studies was aveR, located in the avermectin gene cluster, encoding a LAL-type regulator, and afsS, which is regulated by PhoP and AfsR. The sequence logo for S. avermitilis PHO boxes is similar to that of S. coelicolor, with differences in the weight value for specific nucleotides in the sequence. INTRODUCTIONPhosphate is one of the essential nutrients of all living beings. In early studies, Martín and Demain 1 reported that, following phosphate starvation, there is a change in the metabolism of the antibiotic producing strains, which causes the slowdown of primary metabolism and triggers production of secondary metabolites. This early hypothesis has been largely confirmed by the research developed in the last few decades and is discussed in more detail below taking into account recent developments in the coordination of secondary metabolism. The aim of this article is to present an up-to-date integrative view of the PhoP regulation of metabolism in Streptomyces.

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Section: Cross Regulation Of Nitrogen Metabolism and Phopmentioning

confidence: 99%

The master regulator PhoP coordinates phosphate and nitrogen metabolism, respiration, cell differentiation and antibiotic biosynthesis: comparison in Streptomyces coelicolor and Streptomyces avermitilis

2017

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“…Streptomyces-GlnR homologues are widespread in Streptomyces strains, and GlnR-mediated regulation of nitrogen metabolism is highly conserved among different streptomycetes (6,18). Here, to investigate whether GlnR-dependent regulation of antibiotic biosynthesis is also universal among Streptomyces, the function of GlnRsav (a homologue of GlnR encoded by SAV_4042) in S. avermitilis NRRL 8165 was studied, and a ⌬glnRsav mutant with an inframe deletion of the glnRsav gene was constructed.…”

Section: Glnr-mediated Regulation Of Antibiotic Biosynthesis May Be Hmentioning

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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“…Nucleotides can also be transferred to proteins by Pol β type NTrs. For example, the P II uridylyl transferase (GlnD) in bacteria modifies the P II regulatory protein (GlnB) by uridylylation and deuridylylation [57].…”

Section: Primer Substrate Recognition and Processivitymentioning

confidence: 99%

Determinants of substrate specificity in RNA-dependent nucleotidyl transferases

Martín

Doublié

Keller

2008

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

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Poly(A) polymerases were identified almost fifty years ago as enzymes that add multiple AMP residues to the 3′ ends of primer RNAs without use of a template from ATP as cosubstrate and with release of pyrophosphate. Based on sequence homology of a signature motif in the catalytic domain, poly(A) polymerases were later found to belong to a superfamily of nucleotidyl transferases acting on a very diverse array of substrates. Enzymes belonging to the superfamily can add from single nucleotides of AMP, CMP or UMP to RNA, antibiotics and proteins but also homopolymers of many hundred residues to the 3′ ends of RNA molecules.The recently reported structures of several nucleotidyl transferases facilitate the study of the catalytic mechanisms of these very diverse enzymes. Numerous structures of CCA-adding enzymes have now revealed all steps in the formation of a CCA tail at the 3′ end of tRNAs. In addition, structures of poly(A) polymerases and uridylyl transferases are now available as binary and ternary complexes with incoming nucleotide and RNA primer. Some of these proteins undergo significant conformational changes after substrate binding. This is proposed to be an indication for an induced fit mechanism that drives substrate selection and leads to catalysis. Insights from recent structures of ternary complexes indicate an important role for the primer molecule in selecting the incoming nucleotide.

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Nitrogen Metabolism in <i>Streptomyces coelicolor</i>: Transcriptional and Post-Translational Regulation

Cited by 87 publications

References 61 publications

The master regulator PhoP coordinates phosphate and nitrogen metabolism, respiration, cell differentiation and antibiotic biosynthesis: comparison in Streptomyces coelicolor and Streptomyces avermitilis

The master regulator PhoP coordinates phosphate and nitrogen metabolism, respiration, cell differentiation and antibiotic biosynthesis: comparison in Streptomyces coelicolor and Streptomyces avermitilis

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

Determinants of substrate specificity in RNA-dependent nucleotidyl transferases

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