Impact of the Transcriptional Regulator SCO7424 Overexpression on Antibiotic Production in Streptomyces coelicolor

<b>Background.</b> The genus <i>Streptomyces</i> is known for its capability to produce a wide range of bioactive secondary metabolites. The enzymes required for their synthesis are encoded within biosynthetic gene clusters (BGCs), whose expression can be influenced by various physical and nutritional factors. Among these nutritional factors, it is worth highlighting carbon catabolic repression (CCR), which prevents the formation of secondary metabolites. It has been shown that transcriptional factors, in turn, regulated by glucose or by the enzyme glucose kinase (Glk), may be involved in this mechanism. It was shown that the expression of some transcriptional factors is regulated by glucose availability and that the enzyme glucose kinase (Glk) may play a role in this process. One of the transcriptional factors most upregulated in the presence of glucose/agar in <i>Streptomyces coelicolor</i> M145 is SCO7424, a member of the MarR family of transcriptional regulators. However, its influence on antibiotic synthesis has never been studied. <b>Objective.</b> In this work, we evaluated the effect of SCO7424 overexpression on the synthesis of actinorhodin (ACT) and undecylprodigiosin (RED), and its impact on growth and glucose consumption. <b>Methods.</b> A copy of the <i>sco7424</i> gene was cloned into the pIJ702 plasmid, which was then transformed into a wild-type strain of <i>S. coelicolor</i> M145. Growth and antibiotic production were evaluated in the strain with two copies of <i>sco7424</i> and in the wild-type strain. We also evaluated the expression of the probable target genes by quantitative RT-PCR. <b>Results</b>. We found that overexpression of <i>sco7424</i> negatively impacts growth, glucose consumption kinetics, and the expression of specific regulators of the ACT and RED biosynthetic pathways, resulting in reduced ACT and RED production. Understanding the function of the regulatory cascades regulated by this family of regulators is crucial for boosting the yields of valuable metabolites produced by industrial strains.