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See detailFeast or famine: the global regulator DasR links nutrient stress to antibiotic production by Streptomyces
Rigali, Sébastien ULg; Titgemeyer, Fritz; Barends, Sharief et al

in EMBO Reports (2008), 9(7), 670-675

Members of the soil-dwelling prokaryotic genus Streptomyces produce a wealth of secondary metabolites, including antibiotics and anti-tumour agents. Their formation is intimately coupled with the onset of ... [more ▼]

Members of the soil-dwelling prokaryotic genus Streptomyces produce a wealth of secondary metabolites, including antibiotics and anti-tumour agents. Their formation is intimately coupled with the onset of development, triggered by the nutrient status of the habitat. We propose the first complete signalling cascade from nutrient sensing to development and antibiotic biosynthesis. We show that a high concentration of N-acetylglucosamine - perhaps mimicking the accumulation of N-acetylglucosamine after autolytic degradation of the vegetative mycelium - is a major checkpoint for the onset of secondary metabolism. The response is transmitted to the antibiotic pathway-specific activators via the pleiotropic transcriptional repressor DasR, whose regulon also includes all N-acetylglucosamine-related catabolic genes. The results have led to a new strategy for activating “cryptic” pathways for secondary metabolite biosynthesis, which are abundant in actinomycete genomes, thereby offering new prospects in the fight against multiply drug resistant pathogens and cancers. [less ▲]

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See detailMethods and means for metabolic engineering and improved product formation by micro-organisms
Rigali, Sébastien ULg; Titgemeyer, Fritz; van Wezel, Gilles

Patent (2007)

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See detailPREDetector: A new tool to identify regulatory elements in bacterial genomes
Hiard, Samuel ULg; Marée, Raphaël ULg; Colson, Séverine ULg et al

in Biochemical and Biophysical Research Communications (2007), 357(4), 861-864

In the post-genomic area, the prediction of transcription factor regulons by position weight matrix-based programmes is a powerful approach to decipher biological pathways and to modelize regulatory ... [more ▼]

In the post-genomic area, the prediction of transcription factor regulons by position weight matrix-based programmes is a powerful approach to decipher biological pathways and to modelize regulatory networks in bacteria. The main difficulty once a regulon prediction is available is to estimate its reliability prior to start expensive experimental validations and therefore trying to find a way how to identify true positive hits from an endless list of potential target genes of a regulatory protein. Here we introduce PREDetector (Prokaryotic Regulatory Elements Detector), a tool developed for predicting regulons of DNA-binding proteins in bacterial genomes that, beside the automatic prediction, scoring and positioning of potential binding sites and their respective target genes in annotated bacterial genomes, it also provides an easy way to estimate the thresholds where to find reliable possible new target genes. PREDetector can be downloaded freely at http://www.montefiore.ulg.ac.be/-hiard/PreDetector (c) 2007 Published by Elsevier Inc. [less ▲]

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See detailFrom dormant to germinating spores of Streptomyces coelicolor A3(2): new perspectives from the crp null mutant.
Piette, André ULg; Derouaux, Adeline ULg; Gerkens, Pascal et al

in Journal of Proteome Research (2005), 4(5), 1699-708

The complete understanding of the morphological differentiation of streptomycetes is an ambitious challenge as diverse sensors and pathways sensitive to various environmental stimuli control the process ... [more ▼]

The complete understanding of the morphological differentiation of streptomycetes is an ambitious challenge as diverse sensors and pathways sensitive to various environmental stimuli control the process. Germination occupies a particular position in the life cycle as the good achievement of the process depends on events occurring both during the preceding sporulation and during germination per se. The cyclic AMP receptor protein (crp) null mutant of Streptomyces coelicolor, affected in both sporulation and germination, was therefore presented as a privileged candidate to highlight new proteins involved in the shift from dormant to germinating spores. Our multidisciplinary approach-combining in vivo data, the analysis of spores morphological properties, and a proteome study-has shown that Crp is a central regulatory protein of the life cycle in S. coelicolor; and has identified spores proteins with statistically significant increased or decreased expression that should be listed as priority targets for further investigations on proteins that trigger both ends of the life cycle. [less ▲]

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See detailCrp of Streptomyces Coelicolor Is the Third Transcription Factor of the Large Crp-Fnr Superfamily Able to Bind Camp
Derouaux, Adeline ULg; Dehareng, Dominique ULg; Lecocq, Elke et al

in Biochemical and Biophysical Research Communications (2004), 325(3), 983-90

The chromosomal inactivation of the unique transcription factor of Streptomyces coelicolor that displays a cyclic-nucleotide-binding domain, Crp(Sco), led to a germination-defective phenotype similar to ... [more ▼]

The chromosomal inactivation of the unique transcription factor of Streptomyces coelicolor that displays a cyclic-nucleotide-binding domain, Crp(Sco), led to a germination-defective phenotype similar to the mutant of the adenylate cyclase gene (cya) unable to produce cAMP. By means of cAMP affinity chromatography we demonstrate the specific cAMP-binding ability of Crp(Sco), which definitely demonstrate that a Cya/cAMP/Crp system is used to trigger germination in S. coelicolor. However, electromobility shift assays with the purified Crp(Sco)-cAMP complex and the CRP-like cis-acting element of its own promoter failed. Moreover, we were unable to complement an Escherichia coli crp mutant in trans with Crp(Sco). The fact that Vfr from Pseudomonas aeruginosa and GlxR from Corynebacterium glutamicum could complement such an E. coli mutant suggests that the way Crp(Sco) interacts with DNA should mechanistically differ from its most similar members. This hypothesis was further supported by homology modelling of Crp(Sco) that confirmed an unusual organisation of the DNA-binding domain compared to the situation observed in Crp(Eco). [less ▲]

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See detailRôle pléiotrope de la protéine CRP chez Streptomyces coelicolor
Derouaux, Adeline ULg; Titgemeyer, Fritz; Dusart, Jean et al

Conference (2004)

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See detailStudy of the crp-like gene of Streptomyces coelicolor
Derouaux, Adeline ULg; Titgemeyer, Fritz; Dusart, Jean et al

Poster (2003)

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