The analysis of the inorganic phosphate effect over the antibiotics production is a long-distance history in the Streptomyces genus, which began almost at the same time that Michael Ende published his book entitled The Neverending Story. In some way, the unveiling of the pho regulon and its influence over the secondary metabolites production is an unfinished story, which keeps this subject as a trending topic, nowadays. Up to date, different studies have been releasing knowledge about particular areas of the pho regulon of different Streptomyces species. Nevertheless, for the first time, these knowledge drops are grouped in a review presenting a broad overview of the phosphate regulation and its impact over the secondary metabolites production in industrially relevant species. Even though the genetic response against phosphate scarcity is similar, as a whole, in different Streptomyces species, the fine-tuning is species-specific. Thus, the response regulator PhoP directly controls the secondary metabolites production in some species, whereas it regulates them in an indirect manner in other species. This information, unraveled in this review, is the result of the intensive analysis along last decade in several species of the genus that is allowing to distinguish how the phosphate response is unleashed in Streptomyces coelicolor, Streptomyces lividans, Streptomyces natalensis, Streptomyces lydicus, Streptomyces avermitilis, and Streptomyces tsukubaensis.
Keywords: Antibiotics; Phosphate; Regulation; Secondary metabolites; Streptomyces; pho regulon.