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The 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  .   c   oelicolor    r   egulator ), 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.

The XRE-DUF397 Protein Pair, Scr1 and Scr2, Acts as a Strong Positive Regulator of Antibiotic Production in Streptomyces