The sugar phosphotransferase system of Streptomyces coelicolor is regulated by the GntR‐family regulator DasR and links N‐acetylglucosamine metabolism to the control of development

Abstract

SummaryMembers of the soil-dwelling, sporulating prokaryotic genus Streptomyces are indispensable for the recycling of the most abundant polysaccharides on earth (cellulose and chitin), and produce a wide range of antibiotics and industrial enzymes. How do these organisms sense the nutritional state of the environment, and what controls the signal for the switch to antibiotic production and morphological development? Here we show that high extracellular concentrations of N-acetylglucosamine, the monomer of chitin, prevent Streptomyces coelicolor progressing beyond the vegetative state, and that this effect is absent in a mutant defective of N-acetylglucosamine transport. We provide evidence that the signal is transmitted through the GntR-family regulator DasR, which controls the N-acetylglucosamine regulon, including the pts genes ptsH, ptsI and crr needed for uptake of N-acetylglucosamine. Deletion of dasR or the pts genes resulted in a bald phenotype. Binding of DasR to its target genes is abolished by glucosamine 6-phosphate, a central molecule in N-acetylglucosamine metabolism. Extracellular complementation experiments with many bld mutants showed that the dasR mutant is arrested at an early stage of the developmental programme, and does not fit in the previously described bld signalling cascade. Thus, for the first time we are able to directly link carbon (and nitrogen) metabolism to development, highlighting a novel type of metabolic regulator, which senses the nutritional state of the habitat, maintaining vegetative growth until changing circumstances trigger the switch to sporulation. Our work, and the model it suggests, provide new leads towards understanding how microorganisms time developmental commitment.

Carbon source regulation of antibiotic production

“…This effect is absent in a mutant defective in GlcNAc transport. 109 Therefore, transcription of nagE2 is induced by GlcNAc but repressed by DasR.…”

“…The effector molecule is GlcN-6-P, thus upon binding to GlcN-6-P, DasR is released from its target genes, 109 relieving the inhibition of antibiotic production and morphological differentiation. This effect is absent in a mutant defective in GlcNAc transport.…”

“…109,110 The manner by which it does that is yet unclear, but it is most likely primarily due to a complete upset of primary metabolism rather than the control of developmental genes, such as the bld or whi genes (GP van Wezel, personal communication). As an example, one of the major targets of DasR control besides the pts and nag regulons is the dasABCD chitobiose utilization operon that lies immediately adjacent to (and is oppositely oriented toward) dasR.…”

Extracellular sugar phosphates are assimilated by Streptomyces in a PhoP-dependent manner

“…Although the role of ubiquist molecules in signalisation has been poorly investigated, several studies confirmed that these molecules are likely to signal specific metabolic state and thus also play important regulatory roles (Viollier et al 2001a, b;Li et al 2008;Rigali et al 2008;Luti and Mavituna 2011). For instance, we have previously demonstrated that the peptidoglycan aminosugar building block N-acetylglucosamine (GlcNAc) has a different impact on development depending on the nutritional context and its concentration (Rigali et al 2006(Rigali et al , 2008Nothaft et al 2010;Craig et al 2012;Swiatek et al 2012).…”

PREDetector: A new tool to identify regulatory elements in bacterial genomes

“…Once regulatory DNA sequences have been demonstrated as targets for a specific transcription factor, their conserved signature is generally described by position weight matrices (PWMs) which specify the frequency distribution of nucleotides at each position of the TF cis-acting elements. Several PWMs based web tools (such as Target Explorer [1], Virtual Footprint [2], or PredictRegulon [3]) have directed experimental investigation by highlighting potential new target genes of a transcription factor [4], defining a regulon in closely related bacterial species, and also have contributed to revealing new cis-trans relationships [5]. The diversity and complexity of in vivo cis-trans relationships make computational predictions of transcription factors regulons hazardous.…”