A New TetR Family Transcriptional Regulator Required for Morphogenesis inStreptomyces coelicolor

Abstract

Both morphogenesis and antibiotic production in the streptomycetes are initiated in response to starvation, and these events are coupled. We previously described a transposon-generated mutant in Streptomyces coelicolor, SE293, that resulted in a bld strain that overproduced the antibiotic actinorhodin. The SCO1135 open reading frame identified by the insertion encodes a member of the TetR family of transcriptional regulators. Here we show that a constructed deletion of the SCO1135 open reading frame resulted in the same morphological and antibiotic production phenotype as the insertion mutant. The constructed deletion also resulted in constitutive expression of SCO1135 transcript, as well as that of the gene cluster immediately adjacent to it, SCO1134-1132, which encodes a putative molybdopterin binding complex. A His 6 -tagged version of the SCO1135 protein product was shown to bind the intergenic region between SCO1135 and SCO1134, which contains the apparent transcription start sites for each gene mapped by primer extension analysis. Increased expression of the SCO1134-1132 transcript in the SCO1135 deletion mutant also resulted in increased expression of xanthine dehydrogenase activity, confirming the predictions about these open reading framed based on protein similarity. We have designated the SCO1134-1142 gene cluster xdhABC and the regulator encoded by SCO1135 xdhR. We speculate that the inappropriate expression of xanthine dehydrogenase affects purine salvaging pathways at the onset of development, creating artificially high concentrations of both GTP and ppGpp and perturbing the pathways these molecules participate in for the initiation of morphogenesis and antibiotic production.

The TetR Family of Regulators

“…Xanthine dehydrogenase activity is responsible for the conversion of xanthine to uric acid, which can be broken down and used as a nitrogen source. XdhR may therefore provide a link between primary metabolism, morphological development, and antibiotic production in Streptomyces (156), and our analysis shows that XdhR is indeed well conserved in this genus. The potato pathogen Streptomyces scabies carries two xdhR homologs (Fig.…”

Cif Is Negatively Regulated by the TetR Family Repressor CifR

“…The family of TetR repressors has been shown to regulate the expression of genes involved in a variety of pathways, from antibiotic resistance to carbon catabolism (20,23,36). Typically TetR family members have a DNA-binding helix-turnhelix (HTH) motif as well as an effector-binding domain.…”

CebR as a Master Regulator for Cellulose/Cellooligosaccharide Catabolism Affects Morphological Development in Streptomyces griseus

“…WhiH is specifically needed for the orderly multiple-sporulation septation of aerial hyphae (34). Many DNAbinding proteins have recently been identified as regulators of morphological development in S. coelicolor A3(2): a TetR family regulator (XdhR) (12), an AsnC family regulator (BkdR) (42), two IclR family regulators (SamR [45] and SsgR [46]), and three GntR family regulators (DevA [15], DasR [32], and Agl3R [11]). In particular, DasR and Agl3R are regulators of carbon source utilization.…”