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Identification of glucose kinase‐dependent and ‐independent pathways for carbon control of primary metabolism, development and antibiotic production in S treptomyces coelicolor by quantitative proteomics
Author(s) -
Gubbens Jacob,
Janus Marleen,
Florea Bogdan I.,
Overkleeft Herman S.,
Wezel Gilles P.
Publication year - 2012
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.12072
Subject(s) - catabolite repression , streptomyces coelicolor , biology , secondary metabolism , biochemistry , enzyme , streptomyces , nutrient sensing , metabolic pathway , actinorhodin , signal transduction , biosynthesis , bacteria , genetics , gene , mutant
Summary Members of the soil‐dwelling prokaryotic genus S treptomyces are indispensable for the recycling of complex polysaccharides, and produce a wide range of natural products. Nutrient availability is a major determinant for the switch to development and antibiotic production in streptomycetes. Carbon catabolite repression ( CCR ), a main signalling pathway underlying this phenomenon, was so far considered fully dependent on the glycolytic enzyme glucose kinase ( Glk ). Here we provide evidence of a novel Glk ‐independent pathway in S treptomyces coelicolor , using advanced proteomics that allowed the comparison of the expression of some 2000 proteins, including virtually all enzymes for central metabolism. While CCR and inducer exclusion of enzymes for primary and secondary metabolism and precursor supply for natural products is mostly mediated via Glk , enzymes for the urea cycle, as well as for biosynthesis of the γ‐butyrolactone Scb 1 and the responsive cryptic polyketide Cpk are subject to Glk ‐independent CCR . Deletion of glkA led to strong downregulation of biosynthetic proteins for prodigionins and calcium‐dependent antibiotic ( CDA ) in mannitol‐grown cultures. Repression of bldB , bldN , and its target bldM may explain the poor development of S . coelicolor on solid‐grown cultures containing glucose. A new model for carbon catabolite repression in streptomycetes is presented.