A proteomic study to elucidate molecular relationships between iron, oxidative stress and polyphosphate in Streptomyces coelicolor A3(2)

Polyphosphate (polyP) is an important energy and phosphate storage polymer present in all organisms. In Streptomyces, the deletion of the polyP kinase (PPK) gene resulted in an antibiotic-overproducing phenotype. However, the industrial use of overproducing ∆ppk Streptomyces strains is hampered by their increased sensitivity to oxidative stress, likely indicating an increase in their internal oxidative stress. Iron is an essential element for various cellular processes, yet excess iron generates oxidative stress, particularly via the Fenton reaction. Interestingly, polyP can sequester iron, reducing its bioavailability and thus oxidative stress. The aim of this study was to elucidate the relationships between polyP metabolism, iron homeostasis and oxidative stress in Streptomyces coelicolor. To achieve this, comparative proteomic analyses were conducted on three biological replicates of wild-type (WT) and ∆ppk strains grown in iron-containing and iron-free media. The results indicated that even in the absence of iron, the deletion of ppk significantly altered the total proteome, thereby confirming the importance of PPK in the cellular metabolism. For instance, proteins involved in energy metabolism and protein folding were more abundant in the ∆ppk mutant than in the WT. In the presence of iron the abundance of the proteins involved in phosphate metabolism, oxidative stress response, and translation was higher in the ∆ppk mutant strain than in the WT. To the best of our knowledge, this is the first study to elucidate the relationship between iron homeostasis, oxidative stress, and polyphosphate in Streptomyces.