AUTHOR=Santamaría Ramón I. , Sevillano Laura , Martín Jesús , Genilloud Olga , González Ignacio , Díaz Margarita 

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

JOURNAL=Frontiers in Microbiology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2018.02791

DOI=10.3389/fmicb.2018.02791

ISSN=1664-302X

ABSTRACT=<p>The xenobiotic response element (XRE) transcription factors belong to a regulator family frequently found in <italic>Streptomyces</italic> 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 <italic>SCO4441</italic> and <italic>SCO4442</italic> of <italic>Streptomyces coelicolor</italic>, and denominated Scr1/Scr2 (which stands for <bold><underline>S</underline></bold>. <bold><underline>c</underline></bold><italic>oelicolor</italic><bold><underline>r</underline></bold><italic>egulator</italic>), 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 <italic>S. coelicolor</italic>. The analysis of the 19 <italic>Streptomyces</italic> strains tested determined that overexpression of the pair Scr1/Scr2 drastically induces the production of antibiotics not only in <italic>S. coelicolor</italic>, but also in <italic>Streptomyces lividans</italic>, <italic>Streptomyces peucetius, Streptomyces steffisburgensis</italic> and <italic>Streptomyces</italic> sp. CA-240608. Our work also shows that Scr1 needs Scr2 to exert positive regulation on antibiotic production.</p>