ClpP-dependent degradation of PopR allows tightly regulated expression of the clpP3 clpP4 operon in Streptomyces lividans.

Five clpP genes have been identified in Streptomyces coelicolor. The clpP1 and clpP2 genes form one operon, the clpP3 and clpP4 genes form another, and clpP5 is monocistronic. Previous studies in Streptomyces lividans have shown that the first operon (clpP1 clpP2) is required for a normal cell cycle. Expression of the second operon (clpP3 clpP4) is activated by PopR if the first operon is nonfunctional. We show here that PopR degradation is primarily dependent on ClpP1 and ClpP2, but can also be achieved by ClpP3 and ClpP4. The carboxy-terminus of PopR plays an essential part in the degradation process. Indeed, replacement of the last two alanine residues by aspartate residues greatly increased PopR stability. These substitutions did not impair PopR activity and, as expected, accumulation of the mutant form of PopR led to very strong expression of the clpP3 clpP4 operon. Increased PopR levels led to delayed sporulation. The results obtained in this study support the notion of cross-processing between ClpP1 and ClpP2.