Data_Sheet_1_The XRE-DUF397 Protein Pair, Scr1 and Scr2, Acts as a Strong Positive Regulator of Antibiotic Production in Streptomyces.PDF

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. 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.

异生物反应元件（XRE）转录因子属于在链霉菌属中常见的调控因子家族，其后通常跟随含有DUF397结构域的小型蛋白质。事实上，XRE-DUF397这对因子已被提出可能构成毒素-抗毒素（TA）II型系统。在本研究中，我们展示了其中一种假定的TA系统，由链霉菌紫色素（Streptomyces coelicolor）中的SCO4441和SCO4442基因编码，并命名为Scr1/Scr2（代表S. coelicolor调控因子），在所使用的条件下并未表现出原本预期的毒素-抗毒素系统的行为。相反，Scr1/Scr2这对因子在S. coelicolor中充当内源性抗生素生产的强正调控因子。对19个链霉菌菌株的分析表明，Scr1/Scr2的过表达剧烈诱导了抗生素的产生，这不仅发生在S. coelicolor中，还发生在链霉菌深色（Streptomyces lividans）、链霉菌波西提亚（Streptomyces peucetius）、链霉菌斯蒂菲堡（Streptomyces steffisburgensis）以及链霉菌种CA-240608中。我们的工作还表明，Scr1需要Scr2来对抗生素生产实施正调控。