TheROK-family regulatorRok7B7directly controls carbon catabolite repression, antibiotic biosynthesis, and morphological development inStreptomyces avermitilis

Carbon catabolite repression (CCR) is a common phenomenon in bacteria that modulates expression of genes involved in uptake of alternative carbon sources. In the filamentous streptomycetes, which produce half of all known antibiotics, the precise mechanism of CCR is yet unknown. We report here that the ROK-family regulator Rok7B7 pleiotropically controls xylose and glucose uptake, CCR, development, as well as production of the macrolide antibiotics avermectin and oligomycin A inStreptomyces avermitilis. Rok7B7 directly repressed structural genes for avermectin biosynthesis, whereas it activatedolmRI, the cluster-situated activator gene for oligomycin A biosynthesis. Rok7B7 also directly repressed the xylose uptake operonxylFGH, whose expression was induced by xylose and repressed by glucose. Both xylose and glucose served as Rok7B7 ligands.rok7B7deletion led to enhancement and reduction of avermectin and oligomycin A production, respectively, relieved CCR ofxylFGH, and increased co-uptake efficiency of xylose and glucose. A consensus Rok7B7-binding site, 5 '-TTKAMKHSTTSAV-3 ', was identified withinaveA1p,olmRIp, andxylFp, which allowed prediction of the Rok7B7 regulon and confirmation of 11 additional targets involved in development, secondary metabolism, glucose uptake, and primary metabolic processes. Our findings will facilitate methods for strain improvement, antibiotic overproduction, and co-uptake of xylose and glucose inStreptomycesspecies.