Feast or famine: the global regulator DasR links nutrient stress to antibiotic production by Streptomyces

Members of the soil‐dwelling prokaryotic genus Streptomyces produce many secondary metabolites, including antibiotics and anti‐tumour agents. Their formation is coupled with the onset of development, which is triggered by the nutrient status of the habitat. We propose the first complete signalling c...

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Bibliographic Details
Published in:EMBO reports 2008-07, Vol.9 (7), p.670-675
Main Authors: Rigali, Sébastien, Titgemeyer, Fritz, Barends, Sharief, Mulder, Suzanne, Thomae, Andreas, Hopwood, David, van Wezel, Gilles
Format: Article
Language:English
Subjects:
Acetylglucosamine - metabolism
Anti-Bacterial Agents - biosynthesis
antibiotic production
Antibiotics
Bacterial Proteins - metabolism
Biochemistry
Biochemistry, biophysics & molecular biology
Biochimie, biophysique & biologie moléculaire
biophysics
Biosynthesis
Culture Media
DasR
development
EMBO06
EMBO11
Famine
Life sciences
Metabolites
Microbiologie
Microbiology
Molecular biology
N-acetylglucosamine
nutrient sensing
Nutrient status
Nutrients
Pathogens
regulation
Sciences du vivant
Scientific Report
secondary metabolism
secondary metabolite
Secondary metabolites
Signal Transduction
signalling
signalling cascade
Soil microorganisms
Streptomyces
Streptomyces coelicolor - metabolism
Stress
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Summary:Members of the soil‐dwelling prokaryotic genus Streptomyces produce many secondary metabolites, including antibiotics and anti‐tumour agents. Their formation is coupled with the onset of development, which is 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 antibiotic pathway‐specific activators through the pleiotropic transcriptional repressor DasR, the regulon of which also includes all N ‐acetylglucosamine‐related catabolic genes. The results allowed us to devise a new strategy for activating pathways for secondary metabolite biosynthesis. Such ‘cryptic’ pathways are abundant in actinomycete genomes, thereby offering new prospects in the fight against multiple drug‐resistant pathogens and cancers.
ISSN:1469-221X
1469-3178
1469-3178
1469-221X
DOI:10.1038/embor.2008.83