Dual positive feedback regulation of protein degradation of an extra-cytoplasmic function σ factor for cell differentiation in Streptomyces coelicolor

Abstract

Here we report that in Streptomyces coelicolor, the protein stability of an ECF σfactor SigT, which is involved in the negative regulation of cell differentiation, was completely dependent on its cognate anti-σ factor RstA. The degradation of RstA caused a ClpP/SsrA-dependent degradation of SigT during cell differentiation. This was consistent with the delayed morphological development or secondary metabolism in the ΔclpP background after rstA deletion or sigT overexpression. Meanwhile, SigT negatively regulated clpP/ssrA expression by directly binding to the clpP promoter (clpPp). The SigT-clpPp interaction could be disrupted by secondary metabolites, giving rise to the stabilized SigT protein and retarded morphological development in a non-antibiotic-producing mutant. Thus a novel regulatory mechanism was revealed that the protein degradation of the ECF σfactor was initiated by the degradation of its anti-σfactor, and was accelerated in a dual positive feedback manner, through regulation by secondary metabolites, to promote rapid and irreversible development of the secondary metabolism. This ingeniouscooperationofintracellularcomponentscanensureeconomical and exquisite control of the ECF σfactor protein level for the proper cell differentiation in Streptomyces. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.