The orphan response regulator Aor1 from Streptomyces coelicolor is a new piece in the puzzle of the regulation network of antibiotic production

Abstract

[Backgrounds]: Antibiotic production in Streptomyces coelicolor responds to different environmental signals, both physicals (pH, temperature...) and chemicals (nutrients, activators...), through a complex signalling network. Recognisance of these stimuli is performed mainly through Two Component Systems (TCS). Usually, TCSs are composed by a histidine kinase (HK) and a response regulator (RR), forming a single operon in the genome, but also exist HKs and RRs without its partner, the so-called orphans. Presence of orphan genes may serve as a way of increasing the response capacity in the cell, expanding regulatory network's complexity. [Objectives]: In this work we try to elucidate the role of one of these orphan regulators, Aor1 (Antibiotic Orphan Regulator), that apparently has great importance in antibiotic production in S. coelicolor and differentiation. [Methods]: We have obtained the deletion mutant (ΔSCO2281) in S. coelicolor that allowed us to demonstrate that this orphan RR is involved in the positive regulation of antibiotic production and differentiation. This mutant is drastically affected in endogenous antibiotic biosynthesis of actinorhodin, undecilprodigiosin and calcium dependent antibiotic. We have also evidence that shows a possible relation between this RR and the TCS AbrC. On the other hand, we have demonstrated, by q-RTPCR, that gene aor1 is part of a four gene operon (SCO2279-2282). [Conclusions]: RR Aor1 seems to have an important role in antibiotic production in S. coelicolor, and its study adds significant information about this main piece in the puzzle that could serve for unveiling the complex antibiotic regulatory network in Streptomyces.