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

• Published in: EMBO reports Vol. 9; no. 7; pp. 670 - 675
• Main Authors: Rigali, Sébastien, Titgemeyer, Fritz, Barends, Sharief, Mulder, Suzanne, Thomae, Andreas, Hopwood, David, van Wezel, Gilles
• Format: Journal Article Web Resource
• Language: English
• Published: Chichester, UK Nature Publishing Group 01.07.2008; John Wiley & Sons, Ltd; Nature Publishing Group UK; Blackwell Publishing Ltd
• 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; development; regulation; secondary metabolism; signalling; nutrient sensing
• ISSN: 1469-221X; 1469-3178; 1469-3178; 1469-221X
• DOI: 10.1038/embor.2008.83

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.