Genome-Wide Analysis of In Vivo Binding of the Master Regulator DasR in Streptomyces coelicolor Identifies Novel Non-Canonical Targets

Streptomycetes produce a wealth of natural products, including over half of all known anti-biotics. It was previously demonstrated that N-acetylglucosamine and secondary metabo- lism are closely entwined in streptomycetes. Here we show that DNA recognition by the N- acetylglucosamine-responsive regulator DasR is growth-phase dependent, and that DasR can bind to sites in the S. coelicolor genome that have no obvious resemblance to previous- ly identified DasR-responsive elements. Thus, the regulon of DasR extends well beyond what was previously predicted and includes a large number of genes with functions far re- moved from N-acetylglucosamine metabolism, such as genes for small RNAs and DNA transposases. Conversely, the DasR regulon during vegetative growth largely correlates to the presence of canonical DasR-responsive elements. The changes in DasR binding in vivo following N-acetylglucosamine induction were studied in detail and a possible molecular mechanism by which the influence of DasR is extended is discussed. Discussion of DasR binding was further informed by a parallel transcriptome analysis of the respective cultures. Evidence is provided that DasR binds directly to the promoters of all genes encoding path- way-specific regulators of antibiotic production in S. coelicolor, thereby providing an exquisitely simple link between nutritional control and secondary metabolism