A response-regulator-like activator of antibiotic synthesis from Streptomyces coelicolor A3(2) with an amino-terminal domain that lacks a phosphorylation pocket

Guthrie, Ellen P.; Flaxman, Christine S.; White, Janet; Hodgson, David A.; Bibb, Mervyn J.; Chater, Keith F.

doi:10.1099/00221287-144-7-2007

Cited by 42 publications

(54 citation statements)

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“…Earlier results have suggested that undecylprodigiosin production is controlled in S. coelicolor by a linear pathway in which the autoregulated redZ gene activates another positive regulatory gene, redD, which in turn promotes the transcription of Red biosynthetic genes (White and Bibb 1997;Guthrie et al 1998). Consistent with the previously determined relationship of redZ to redD, our microarray data show that transcription of these genes is independent of RedD function.…”

Section: Microarray Analysis Of Streptomyces Transcription Genes and Desupporting

confidence: 80%

Global analysis of growth phase responsive gene expression and regulation of antibiotic biosynthetic pathways inStreptomyces coelicolorusing DNA microarrays

Huang¹,

Lih²,

Pan³

et al. 2001

Genes Dev.

195

188

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The eubacterial species Streptomyces coelicolor proceeds through a complex growth cycle in which morphological differentiation/development is associated with a transition from primary to secondary metabolism and the production of antibiotics. We used DNA microarrays and mutational analysis to investigate the expression of individual genes and multigene antibiotic biosynthetic pathways during these events. We identified expression patterns in biosynthetic, regulatory, and ribosomal protein genes that were associated highly specifically with particular stages of development. A knowledge-based algorithm that correlates temporal changes in expression with chromosomal position identified groups of contiguous genes expressed at discrete stages of morphological development, inferred the boundaries of known antibiotic synthesis gene loci, and revealed novel physical clusters of coordinately regulated genes. Microarray analysis of RNA from cells mutated in genes regulating synthesis of the antibiotics actinorhodin (Act) and undecylprodigiosin (Red) identified proximate and distant sites that contain putative ABC transporter and two-component system genes expressed coordinately with genes of specific biosynthetic pathways and indicated the existence of two functionally and physically discrete regulons in the Red pathway.

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Section: Microarray Analysis Of Streptomyces Transcription Genes and Desupporting

confidence: 80%

Global analysis of growth phase responsive gene expression and regulation of antibiotic biosynthetic pathways inStreptomyces coelicolorusing DNA microarrays

Huang¹,

Lih²,

Pan³

et al. 2001

Genes Dev.

195

188

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“…Although these results do not rule out the possibility that FruA is phosphorylated, our discovery of potent cooperative binding by recombinant (presumably unphosphorylated) FruA and MrpC2, which depends on the N-terminal domain of FruA, reveals an unusual function of a receiver domain that may not be phosphorylated. Receiver domains that cannot or need not be phosphorylated in order for the pseudoresponse regulator protein to function have been described in bacterial DNA-binding proteins (32)(33)(34) and in proteins that regulate circadian rhythms in bacteria (35,36) and plants (37).…”

Section: Discussionmentioning

confidence: 99%

A combination of unusual transcription factors binds cooperatively to control Myxococcus xanthus developmental gene expression

Mittal

Kroos

2009

Proc. Natl. Acad. Sci. U.S.A.

144

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Myxococcus xanthus is a bacterium that undergoes multicellular development requiring coordinate regulation of multiple signaling pathways. One pathway governs aggregation and sporulation of some cells in a starving population and requires C-signaling, whereas another pathway causes programmed cell death and requires the MazF toxin. In response to starvation, the levels of the bifunctional transcription factor/antitoxin MrpC and its related proteolytic fragment MrpC2 are increased, inhibiting the cell death pathway via direct interaction of MrpC with MazF. Herein, we demonstrate that MrpC2 plays a direct role in the transcriptional response to C-signaling. We show that MrpC2 binds to sequences upstream of the C-signal-dependent fmgA promoter. These sequences are present in other C-signal-dependent promoter regions, indicating a general role for MrpC2 in developmental gene regulation. Association of MrpC and/or MrpC2 with the fmgA promoter region in vivo requires FruA, a protein that is similar to response regulators of 2-component signal transduction systems, but may not be phosphorylated. DNA binding studies showed that this association likely involves an unusual mechanism for a response regulator in which FruA and MrpC2 bind cooperatively to adjacent sites upstream of the fmgA promoter. We propose that this unusual mechanism of combinatorial control allows coordination of morphogenetic C-signaling with starvation signaling and cell death, determining spatiotemporal gene expression and cell fate.bacterial development ͉ C-signaling ͉ cell fate ͉ signal transduction ͉ sporulation

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“…Two of the 23 genes in the cluster (redD and redZ, orange in Fig. 3) have been shown previously to encode pathway-specific regulators (Narva and Feitelson 1990;White and Bibb 1997;Guthrie et al 1998). Of the remaining 21 genes, six have been assigned to 4-methoxy-2,2 P-bipyrrole-5-carboxaldehyde biosynthesis (red in Fig.…”

Section: Genes Responsible For Prodigiosin Productionmentioning

confidence: 99%

Prodigiosin and its potential applications

2015

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Since a decade, there has been a strong consumer demand for more natural products. This has augmented inclination towards substitution of synthetic colorants with natural pigments. Natural pigments not only have the capacity to increase the marketability of products, they also demonstrate valuable biological activities as antioxidants and anticancer agents. There is a long history of exploitation of natural products produced by bacteria as sources of pharmaceutically important, bioactive compounds. Among natural pigments, pigments from microbial sources are potentially suitable alternatives to synthetic pigments. The red pigment prodigiosin (PG) has unusual properties, which have long been documented. The red-pigmented prodiginines are bioactive secondary metabolites produced by both Gram-negative and Gram-positive bacteria. Prodigiosins are characterized by a common pyrrolyl pyrromethene skeleton, and the biological role of these pigments in the producer organisms remains unclear. Bacterial prodigiosins and their synthetic derivatives are effective proapoptotic agents against various cancer cell lines, with multiple cellular targets including multi-drug resistant cells with little or no toxicity towards normal cell lines. However, research into the biology of pigment production will stimulate interest in the bioengineering of strains to synthesize useful prodiginine derivatives. This review article highlights the characteristics and potential applications of prodigiosin pigment from Serratia as prodigiosins are real potential therapeutic drugs.

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A response-regulator-like activator of antibiotic synthesis from Streptomyces coelicolor A3(2) with an amino-terminal domain that lacks a phosphorylation pocket

Cited by 42 publications

References 0 publications

Global analysis of growth phase responsive gene expression and regulation of antibiotic biosynthetic pathways inStreptomyces coelicolorusing DNA microarrays

Global analysis of growth phase responsive gene expression and regulation of antibiotic biosynthetic pathways inStreptomyces coelicolorusing DNA microarrays

A combination of unusual transcription factors binds cooperatively to control Myxococcus xanthus developmental gene expression

Prodigiosin and its potential applications

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