The ROK Family Regulator Rok7B7 Pleiotropically Affects Xylose Utilization, Carbon Catabolite Repression, and Antibiotic Production in Streptomyces coelicolor

Abstract

cMembers of the ROK family of proteins are mostly transcriptional regulators and kinases that generally relate to the control of primary metabolism, whereby its member glucose kinase acts as the central control protein in carbon control in Streptomyces. Here, we show that deletion of SCO6008 (rok7B7) strongly affects carbon catabolite repression (CCR), growth, and antibiotic production in Streptomyces coelicolor. Deletion of SCO7543 also affected antibiotic production, while no major changes were observed after deletion of the rok family genes SCO0794, SCO1060, SCO2846, SCO6566, or SCO6600. Global expression profiling of the rok7B7 mutant by proteomics and microarray analysis revealed strong upregulation of the xylose transporter operon xylFGH, which lies immediately downstream of rok7B7, consistent with the improved growth and delayed development of the mutant on xylose. The enhanced CCR, which was especially obvious on rich or xylose-containing media, correlated with elevated expression of glucose kinase and of the glucose transporter GlcP. In liquid-grown cultures, expression of the biosynthetic enzymes for production of prodigionines, siderophores, and calcium-dependent antibiotic (CDA) was enhanced in the mutant, and overproduction of prodigionines was corroborated by matrixassisted laser desorption ionization-time-of-flight analysis. These data present Rok7B7 as a pleiotropic regulator of growth, CCR, and antibiotic production in Streptomyces.

Carbon Catabolite Regulation of Secondary Metabolite Formation and Morphological Differentiation in Streptomyces coelicolor

“…One additional explanation may depend on the participation of the Rok7b7 transcriptional regulator, which may control Act production. Actually, in the presence of glucose Rok7b7 (sco6008) showed up-regulation (log2 = 2.14) [33]. Indeed, deletion of Rok7b7 (Table 2) delays aerial mycelium formation, caused early Red production and delayed Act production in R5 medium, lacking KH 2 PO 4 , CaCl 2 , and L-proline [34].…”

“…Indeed, deletion of Rok7b7 (Table 2) delays aerial mycelium formation, caused early Red production and delayed Act production in R5 medium, lacking KH 2 PO 4 , CaCl 2 , and L-proline [34]. It seems that Rok7B7 may activate Act biosynthesis [33,34]. In addition to affect antibiotic formation, the Rok7B7 regulator has been referred to have a pleiotropic effect on aerial mycelium formation [33].…”

“…It seems that Rok7B7 may activate Act biosynthesis [33,34]. In addition to affect antibiotic formation, the Rok7B7 regulator has been referred to have a pleiotropic effect on aerial mycelium formation [33].…”

Production of validamycin A from hemicellulose hydrolysate by Streptomyces hygroscopicus 5008

“…Generally, D-xylose could be utilized as carbon and energy source by a few Streptomyces (Noda et al, 2012;Ś wiatek et al, 2013). In this work, compared to the other two sugars, the high VAL-A yield obtained from D-xylose suggested its significant contribution to the VAL-A biosynthesis in corncob hydrolysate.…”

Biochemistry and regulatory functions of bacterial glucose kinases

“…Currently, approximately 5000 ROK-family proteins have been identified so far, mostly in prokaryotes, but family members are found in all kingdoms of life [65].…”