<i>Streptomyces coelicolor</i> XdhR is a direct target of (p)ppGpp that controls expression of genes encoding xanthine dehydrogenase to promote purine salvage

Sivapragasam, Smitha; Grove, Anne

doi:10.1111/mmi.13342

Cited by 16 publications

(25 citation statements)

References 55 publications

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“…This indicates that the xdh gene product is linked to synthesis of (p)ppGpp during starvation [50]. Consistent with this interpretation, xdh expression is also increased in stationary phase in S. coelicolor , whereas inhibition of Xdh with allopurinol attenuates (p)ppGpp production [51]. In Listeria monocytogenes , both hgprt and relA mutants are incapable of synthesizing (p)ppGpp and fail to cause infection in mice [52].…”

Section: Link Between Purine Salvage and Production Of Guanosine Nmentioning

confidence: 90%

The Link between Purine Metabolism and Production of Antibiotics in Streptomyces

Sivapragasam

Grove

2019

Antibiotics

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Stress and starvation causes bacterial cells to activate the stringent response. This results in down-regulation of energy-requiring processes related to growth, as well as an upregulation of genes associated with survival and stress responses. Guanosine tetra- and pentaphosphates (collectively referred to as (p)ppGpp) are critical for this process. In Gram-positive bacteria, a main function of (p)ppGpp is to limit cellular levels of GTP, one consequence of which is reduced transcription of genes that require GTP as the initiating nucleotide, such as rRNA genes. In Streptomycetes, the stringent response is also linked to complex morphological differentiation and to production of secondary metabolites, including antibiotics. These processes are also influenced by the second messenger c-di-GMP. Since GTP is a substrate for both (p)ppGpp and c-di-GMP, a finely tuned regulation of cellular GTP levels is required to ensure adequate synthesis of these guanosine derivatives. Here, we discuss mechanisms that operate to control guanosine metabolism and how they impinge on the production of antibiotics in Streptomyces species.

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Section: Link Between Purine Salvage and Production Of Guanosine Nmentioning

confidence: 90%

The Link between Purine Metabolism and Production of Antibiotics in Streptomyces

Sivapragasam

Grove

2019

Antibiotics

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“…Moreover, it can stimulate transcription stimulation through direct binding to RNA polymerase . However, ppGpp can also regulate gene expression via affecting binding of targets to DNA such as for example, the XdhR repressor thus relieving the xdhABC operon from repression of xanthine degradation in S. coelicolor A3(2) . In any case, the targets of ppGpp involved in actinomycin biosynthesis are unknown, as yet.…”

Section: Discussionmentioning

confidence: 99%

Comparison of actinomycin peptide synthetase formation in Streptomyces chrysomallus and Streptomyces antibioticus

et al. 2018

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Actinomycin peptide synthetase genes constitute two oppositely oriented transcriptional units, acmADR, and acmBC, separated by a non-coding intergenic region. Gene constructs of the intergenic region together with its adjoining gene acmA or acmB from the actinomycin biosynthetic gene cluster of Streptomyces chrysomallus were transferred into Streptomyces lividans TK64. Each construct expressed the respective synthetase indicating divergent promoters. Primer extension revealed for both directions −10 and −35 boxes similar to σ 70 -dependent promoters from Streptomyces and E. coli. No conspicuous regulatory sequences were detected. Accordingly, S. chrysomallus-grown in glucose-containing medium-produced the peptide synthetases AcmA and AcmB/C as well as actinomycin during logarithmic growth phase. Alignments with the corresponding intergenic region of the actinomycin biosynthetic gene cluster in Streptomyces antibioticus identified analogous −10 and −35 boxes of σ 70 consensus sequence. However, in S. antibioticus-cultivated in the same conditions-AcmA and AcmB/C were at maximum activity in late log phase and actinomycin formation peaked in stationary phase. The different patterns of formation of actinomycin and its peptide synthetases encoded by the highly homologous actinomycin biosynthetic gene clusters in S. chrysomallus and S. antibioticus suggest strain-specific control of biosynthesis in agreement with absence of pathway-specific regulatory genes. K E Y W O R D Sactinomycin, peptide synthetases, promoter, regulation, Streptomyces

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“…In the case of the hypoxanthine inducing the XdhR/P H16_RS05055 -controllable system, it is less clear whether hypoxanthine itself interacts with XdhR, due to structural resemblance to xanthine, or if activation of gene expression is mediated by its catabolic product, the primary effector. In Streptomyces coelicolor, hypoxanthine was not able to bind the regulator of the gene cluster encoding xanthine dehydrogenase enzyme 44 . However, in contrast to the S. coelicolor XdhR, which belongs to the TetR family of TRs 45 , the C. necator XdhR is a LTTR that may operate in a different manner.…”

Section: Screening Structurally and Metabolically Related Compoundsmentioning

confidence: 96%

A genome-wide approach for identification and characterisation of metabolite-inducible systems

et al. 2020

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Inducible gene expression systems are vital tools for the advancement of synthetic biology. Their application as genetically encoded biosensors has the potential to contribute to diagnostics and to revolutionise the field of microbial cell factory development. Currently, the number of compounds of biological interest by far exceeds the number of available biosensors. Here, we address this limitation by developing a generic genome-wide approach to identify transcription factor-based inducible gene expression systems. We construct and validate 15 functional biosensors, provide a characterisation workflow to facilitate forward engineering efforts, exemplify their broad-host-range applicability, and demonstrate their utility in enzyme screening. Previously uncharacterised interactions between sensors and compounds of biological relevance are identified by employing the largest reported library of metabolite-responsive biosensors in an automated high-throughput screen. With the rapidly growing genomic data these innovative capabilities offer a platform to vastly increase the number of biologically detectable molecules.

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Streptomyces coelicolor XdhR is a direct target of (p)ppGpp that controls expression of genes encoding xanthine dehydrogenase to promote purine salvage

Cited by 16 publications

References 55 publications

The Link between Purine Metabolism and Production of Antibiotics in Streptomyces

The Link between Purine Metabolism and Production of Antibiotics in Streptomyces

Comparison of actinomycin peptide synthetase formation in Streptomyces chrysomallus and Streptomyces antibioticus

A genome-wide approach for identification and characterisation of metabolite-inducible systems

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