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 in all organisms. Deletion of the polyP synthesising enzyme, polyP kinase (PPK), resulted in an antibiotic overproducing phenotype in Streptomyces . However, the industrial use of overproducing Streptomyces strains without PPK activity (∆ ppk ) is hampered by their increased sensitivity to oxidative stress. Iron plays a key role in the bacterial response to oxidative stress, and it is also an essential element for various processes in the cell. Conversely, polyP can sequester iron, reducing its bioavailability. This study aimed to elucidate the metabolic relationship between oxidative stress, iron, and polyP metabolisms in Streptomyces coelicolor as an example of the communication of cellular regulatory signalling networks. Comparative proteomic analyses were performed on three biological replicates of wild-type and ∆ ppk strains grown in iron-containing and iron-free media. Independent of iron, the results show that the absence of polyP significantly alters the total proteome, revealing the importance of this polymer in maintaining cellular metabolism. The mutant strain was found to have difficulties coping with the iron even in the nutrient-rich medium. Compared to the wild type in the iron-free medium, a general abundance of proteins related to energy metabolism, and protein folding was observed in ∆ ppk . In the presence of iron, the expression of the proteins involved in translation, phosphate metabolism and the antioxidant system was increased in the mutant strain compared to the wild type. To our knowledge, this is the first study to clarify the relationship between iron, oxidative stress, and polyphosphate.