Article (Scientific journals)
Feast or famine: the global regulator DasR links nutrient stress to antibiotic production by Streptomyces
Rigali, Sébastien; Titgemeyer, Fritz; Barends, Sharief et al.
2008In EMBO Reports, 9 (7), p. 670-675
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Keywords :
N-acetylglucosamine; Streptomyces; antibiotic production; DasR; signalling cascade; secondary metabolite
Abstract :
[en] Members of the soil-dwelling prokaryotic genus Streptomyces produce a wealth of secondary metabolites, including antibiotics and anti-tumour agents. Their formation is intimately coupled with the onset of development, 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 the antibiotic pathway-specific activators via the pleiotropic transcriptional repressor DasR, whose regulon also includes all N-acetylglucosamine-related catabolic genes. The results have led to a new strategy for activating “cryptic” pathways for secondary metabolite biosynthesis, which are abundant in actinomycete genomes, thereby offering new prospects in the fight against multiply drug resistant pathogens and cancers.
Disciplines :
Microbiology
Biochemistry, biophysics & molecular biology
Author, co-author :
Rigali, Sébastien  ;  Université de Liège - ULiège > Département des sciences de la vie > Département des sciences de la vie
Titgemeyer, Fritz
Barends, Sharief
Mulder, Suzanne
Thomae, Andreas
Hopwood, David
van Wezel, Gilles
Language :
English
Title :
Feast or famine: the global regulator DasR links nutrient stress to antibiotic production by Streptomyces
Publication date :
2008
Journal title :
EMBO Reports
ISSN :
1469-221X
eISSN :
1469-3178
Publisher :
Nature Publishing Group, London, United Kingdom
Volume :
9
Issue :
7
Pages :
670-675
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
This paper has been commented in Nature Microbiology reviews by Sheilagh Molloy. http://www.nature.com/nrmicro/journal/v6/n8/full/nrmicro1963.html
Available on ORBi :
since 14 September 2009

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