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.
Members 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.
Rigali
Sébastien
S
Department of Biochemistry, Leiden Institute of Chemistry, Leiden University, PO Box 9502, 2300 RA Leiden, the Netherlands.
Nothaft
Harald
H
Noens
Elke E E
EE
Schlicht
Maximilian
M
Colson
Sévrine
S
Müller
Marisa
M
Joris
Bernard
B
Koerten
Henk K
HK
Hopwood
David A
DA
Titgemeyer
Fritz
F
van Wezel
Giles P
GP
D000117:Acetylglucosamine / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics; D005816:Genetic Complementation Test; D005944:Glucosamine / Q000031:analogs & derivatives / Q000494:pharmacology; D019298:Glucose-6-Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D008855:Microscopy, Electron, Scanning / Q000379:methods; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D010770:Phosphotransferases / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D018085:Regulon / Q000235:genetics; D048372:Streptomyces coelicolor / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D013379:Substrate Specificity
D001426:Bacterial Proteins; C001293:glucosamine 6-phosphate; D019298:Glucose-6-Phosphate; D010770:Phosphotransferases; D005944:Glucosamine; D000117:Acetylglucosamine