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Feast or famine: the global regulator DasR links nutrient stress to antibiotic production by Streptomyces
Author(s) -
Rigali Sébastien,
Titgemeyer Fritz,
Barends Sharief,
Mulder Suzanne,
Thomae Andreas W,
Hopwood David A,
van Wezel Gilles P
Publication year - 2008
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/embor.2008.83
Subject(s) - biology , secondary metabolite , secondary metabolism , repressor , regulator , biosynthesis , regulon , antibiotics , gene , genome , n acetylglucosamine , streptomyces , catabolism , nutrient sensing , bacteria , microbiology and biotechnology , biochemistry , genetics , regulation of gene expression , transcription factor , signal transduction , metabolism , enzyme
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.