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Two-component systems (TCSs) are the most important sensing mechanisms in bacteria. In  Streptomyces , TCSs-mediated responses to environmental stimuli are involved in the regulation of antibiotic production. This study examines the individual role of two histidine kinases (HKs), AbrC1 and AbrC2, which form part of an atypical TCS in  Streptomyces coelicolor . qRT-PCR analysis of the expression of both kinases demonstrated that both are expressed at similar levels in NB and NMMP media. Single deletion of  abrC1  elicited a significant increase in antibiotic production, while deletion of  abrC2  did not have any clear effect. The origin of this phenotype, probably related to the differential phosphorylation ability of the two kinases, was also explored indirectly, analyzing the toxic phenotypes associated with high levels of phosphorylated RR. The higher the AbrC3 regulator phosphorylation rate, the greater the cell toxicity. For the first time, the present work shows in  Streptomyces  the combined involvement of two different HKs in the response of a regulator to environmental signals. Regarding the possible applications of this research, the fact that an  abrC1  deletion mutant overproduces three of the  S. coelicolor  antibiotics makes this strain an excellent candidate as a host for the heterologous production of secondary metabolites.

frontiers in microbiology

The two kinases, AbrC1 and AbrC2, of the atypical two-component system AbrC are needed to regulate antibiotic production and differentiation in Streptomyces coelicolor