Proteasome involvement in a complex cascade mediating SigT degradation during differentiation of Streptomyces coelicolor

• Deletion of proteasome blocks protein degradation of SigT.
• RstA protects SigT from degradation independent of proteasome.
• Proteasome mutant shows reduced production of secondary metabolites.
• Feeding of secondary metabolites promotes SigT degradation in proteasome mutant.

In Streptomyces coelicolor, the ECF sigma factor SigT negatively regulates cell differentiation, and is degraded by ClpP protease in a dual positive feedback manner. Here we further report that the proteasome is required for degradation of SigT, but not for degradation of its anti-sigma factor RstA, and RstA can protect SigT from degradation independent of the proteasome. Meanwhile, deletion of the proteasome showed reduced production of secondary metabolites, and the fermentation medium from wild type could promote SigT degradation. Furthermore, overexpression of redD or actII-orf4 in the proteasome-deficiency mutant resulted in SigT degradation and over-production of both undecylprodigiosin and actinorhodin. Therefore the proteasome is required for SigT degradation by affecting the production of secondary metabolites during cell differentiation.