Santamaría, Ramón ISevillano, LauraMartín, JesúsGenilloud, OlgaGonzález, IgnacioDíaz, Margarita2023-01-252023-01-252018-11-161664-302Xhttp://hdl.handle.net/10668/13290The xenobiotic response element (XRE) transcription factors belong to a regulator family frequently found in Streptomyces that are often followed by small proteins with a DUF397 domain. In fact, the pair XRE-DUF397 has been proposed to comprise toxin-antitoxin (TA) type II systems. In this work, we demonstrate that one of these putative TA-systems, encoded by the genes SCO4441 and SCO4442 of Streptomyces coelicolor, and denominated Scr1/Scr2 (which stands for S. coelicolorregulator), does not behave as a toxin-antitoxin system under the conditions used as was originally expected. Instead the pair Scr1/Scr2 acts as a strong positive regulator of endogenous antibiotic production in S. coelicolor. The analysis of the 19 Streptomyces strains tested determined that overexpression of the pair Scr1/Scr2 drastically induces the production of antibiotics not only in S. coelicolor, but also in Streptomyces lividans, Streptomyces peucetius, Streptomyces steffisburgensis and Streptomyces sp. CA-240608. Our work also shows that Scr1 needs Scr2 to exert positive regulation on antibiotic production.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/Streptomycesantibiotic productionpositive regulatortoxin–antitoxinxenobiotic response elementresearch article30524403open access10.3389/fmicb.2018.02791PMC6262351https://doi.org/10.3389/fmicb.2018.02791https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6262351/pdf