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.
Bibliographical note© 2015 Świątek-Połatyńska et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Swiatek-Polatynska, M. A., Bucca, G., Laing, E., Gubbens, J., Titgemeyer, F., Smith, C., Rigali, S., & Wezel, G. P. V. (2015). Genome-wide analysis of in vivo binding of the master regulator DasR in Streptomyces coelicolor identifies novel non-canonical targets. PLoS ONE, 10(4). https://doi.org/10.1371/journal.pone.0122479