A Novel Two-Component System Involved in the Transition to Secondary Metabolism in Streptomyces coelicolor

Abstract

BackgroundBacterial two-component signal transduction regulatory systems are the major set of signalling proteins frequently mediating responses to changes in the environment. They typically consist of a sensor, a membrane-associated histidine kinase and a cytoplasmic response regulator. The membrane-associated sensor detects the environmental signal or stress, whereas the cytoplasmic regulatory protein controls the cellular response usually by gene transcription modulation.Methodology/PrincipalFindingsThe Streptomyces coelicolor two genes operon SCO5784-SCO5785 encodes a two-component system, where SCO5784 encodes a histidine-kinase sensor and SCO5785 encodes a response regulator protein. When the expression level of the regulator gene decreases, the antibiotic synthesis and sporulation is delayed temporarily in addition to some ribosomal genes became up regulated, whereas the propagation of the regulatory gene in high copy number results in the earlier synthesis of antibiotics and sporulation, as well as the down regulation of some ribosomal genes and, moreover, in the overproduction of several extracellular proteins. Therefore, this two-component system in S. coelicolor seems to influence various processes characterised by the transition from primary to secondary metabolism, as determined by proteomic and transcriptomic analyses.Conclusions/SignificancePropagation of SCO5785 in multicopy enhances the production of antibiotics as well as secretory proteins. In particular, the increase in the expression level of secretory protein encoding genes, either as an artefactual or real effect of the regulator, could be of potential usefulness when using Streptomyces strains as hosts for homologous or heterologous extracellular protein production.

Overproduction of a Model Sec- and Tat-Dependent Secretory Protein Elicits Different Cellular Responses in Streptomyces lividans

“…Hybridisation data from RNA extracted at the early stationary phase of growth were very dispersed (not shown), probably due to the bacterial heterogeneity, as observed previously [ 12 , 13 ].…”

“…It has been observed that major secretory protein overproduction, constituted mainly of Sec proteins, was triggered by the presence in high copy number of a two-component system regulator in S . coelicolor [ 13 ], as well as the induction of the stringent response, strongly suggesting that when the cell detects nutrient depletion (amino acids by protein overproduction), the stringent response is triggered.…”

Molecular Regulation of Antibiotic Biosynthesis in Streptomyces

“…These are among 67 two-component systems encoded in the S. coelicolor chromosome (137). Other two-component systems influencing antibiotic production, but not closely linked to antibiotic biosynthetic genes, include the following: CutRS, affecting ACT production (138); EcrA1A2 (SCO2517 and -8), affecting only RED production (139); SCO0203/0204, which interplay with the orphan RR SCO3818 in exerting medium-dependent effects on ACT production (140,141); and SCO5784 and -5, affecting the timing of ACT and RED production and sporulation, possibly through effects on ppGpp synthesis (142). In two surveys of several two-component systems, the AbrA1A2 system acted negatively on production of ACT, RED, and CDA and the formation of aerial mycelium, while the AbrC1C2C3 system, involving two histidine protein kinases, acted positively on all four aspects (143), and RapA1A2 was shown to stimulate ACT and CPK production (140).…”

A two-component system gene SACE_0101 regulates copper homeostasis in Saccharopolyspora erythraea

“…The 16srRNA gene in S. erythraea was used as the positive internal control. RT-qPCR was performed in 25 μL mixtures using a CFX96 ™ real-time PCR detection system (Bio-Rad, Hercules, CA, USA) (Lu et al 2007;Rozas et al 2012;Yu et al 2012). After optimizing the Tm value and Ct value, each sample was analyzed in three replicates.…”