Cross‐talk between two global regulators in Streptomyces: PhoP and AfsR interact in the control of afsS, pstS and phoRP transcription

Santos-Beneit, Fernando; Rodrı́guez-Garcı́a, Antonio; Sola‐Landa, Alberto; Martı́n, Juan F.

doi:10.1111/j.1365-2958.2009.06624.x

Cited by 111 publications

(118 citation statements)

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“…More than 117 genes were up-or downregulated in an afsS disruption mutant (136). Disruption of afsS also causes diminished actinorhodin production during phosphate starvation, an observation underpinned by the finding that AfsR and PhoP bind to overlapping sequences in the promoter region of afsS (82). Although AfsS is usually thought of as a regulator of antibiotic biosynthetic genes, transcriptome analysis showed that it also has major effects on nutritional starvation genes, which might possibly be responsible for the effects on antibiotic production (136).…”

Section: The Afsk/afsr/afss System and A Possible Interface With Hyphmentioning

confidence: 90%

“…Some reported observations are hard to explain. For example, PhoP binds to, and represses, the promoter of afsS, encoding a global activator of antibiotic production (82). This negative effect is counterintuitive since phosphate limitation activates production of ACT and RED, an effect mediated by enhanced transcription of the relevant biosynthetic genes.…”

Section: Phosphate Regulation Of Antibiotic Production In S Coelicolormentioning

confidence: 99%

“…This negative effect is counterintuitive since phosphate limitation activates production of ACT and RED, an effect mediated by enhanced transcription of the relevant biosynthetic genes. Likewise, deletion of phoP causes reduced ACT and RED production under phosphate limitation (82). Another PhoP-repressible gene encodes RpoZ, the omega [69]), Aur1P (auricin, Streptomyces aureofaciens [297]), LanI (landomycins, Streptomyces cyanogenus [298]), and LndI (landomycin E, Streptomyces globisporus [299]).…”

Section: Phosphate Regulation Of Antibiotic Production In S Coelicolormentioning

confidence: 99%

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Molecular Regulation of Antibiotic Biosynthesis in Streptomyces

Liu

Chater

Chandra

et al. 2013

Microbiol Mol Biol Rev

596

536

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SUMMARY Streptomycetes are the most abundant source of antibiotics. Typically, each species produces several antibiotics, with the profile being species specific. Streptomyces coelicolor , the model species, produces at least five different antibiotics. We review the regulation of antibiotic biosynthesis in S. coelicolor and other, nonmodel streptomycetes in the light of recent studies. The biosynthesis of each antibiotic is specified by a large gene cluster, usually including regulatory genes (cluster-situated regulators [CSRs]). These are the main point of connection with a plethora of generally conserved regulatory systems that monitor the organism's physiology, developmental state, population density, and environment to determine the onset and level of production of each antibiotic. Some CSRs may also be sensitive to the levels of different kinds of ligands, including products of the pathway itself, products of other antibiotic pathways in the same organism, and specialized regulatory small molecules such as gamma-butyrolactones. These interactions can result in self-reinforcing feed-forward circuitry and complex cross talk between pathways. The physiological signals and regulatory mechanisms may be of practical importance for the activation of the many cryptic secondary metabolic gene cluster pathways revealed by recent sequencing of numerous Streptomyces genomes.

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Section: The Afsk/afsr/afss System and A Possible Interface With Hyphmentioning

confidence: 90%

Section: Phosphate Regulation Of Antibiotic Production In S Coelicolormentioning

confidence: 99%

Section: Phosphate Regulation Of Antibiotic Production In S Coelicolormentioning

confidence: 99%

See 1 more Smart Citation

Molecular Regulation of Antibiotic Biosynthesis in Streptomyces

Liu

Chater

Chandra

et al. 2013

Microbiol Mol Biol Rev

596

536

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“…PhoP was found to bind a PHO box overlapping with the sequence recognized by AfsR. 36,37 Both PhoP and AfsR are positive regulators and compete for this sequence. Indeed, the affinity of AfsR for this PHO box is higher than that of PhoP, and therefore, PhoP interferes with optimal AfsR-mediated afsS expression.…”

Section: Phop Control Of Antibiotic and Other Secondary Metabolites Bmentioning

confidence: 99%

“…The first direct connection of the PhoP regulator with the control of antibiotic biosynthesis was made by Santos-Beneit et al 36 when they proved that PhoP binds the same sequence in the afsS promoter as the cognate-regulator AfsR. AfsS is a small protein (63 amino acid) that activates expression of actII-orf4 and redD, the cluster situated regulators of the actinorhodin and undecylprodigiosine biosynthetic clusters.…”

Section: Phop Control Of Antibiotic and Other Secondary Metabolites Bmentioning

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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