Engineering the sco1897–sco1901 region affects phosphate homeostasis and remodels specialised metabolism in Streptomyces coelicolor

Abstract Background Phosphate availability plays a central role in the regulation of both morphological differentiation and specialised metabolism in Streptomyces . Because developmental progression and specialised-metabolite production are tightly coordinated processes, understanding the mechanisms that control phosphate homeostasis may provide new opportunities to manipulate specialised metabolism and activate biosynthetic pathways that remain poorly expressed under standard laboratory conditions. We recently identified a link between the SCO1897 regulator and the downstream sco1898–sco1901 region, phosphorus accumulation and the regulation of specialised metabolism. Here, we investigated whether engineering this system could remodel specialised metabolism and unlock otherwise poorly expressed biosynthetic pathways. Results We compared a sco1897::Tn5 mutant and strains overexpressing sco1897 , sco1900 , sco1901 or sco1898–1901 with the plasmid-free wild type and the wild type harbouring the empty overexpression plasmid. These strains exhibited different spore phosphorus contents and metabolomic profiles. Between 2,445 and 5,120 features differed significantly in abundance, including features assigned to specialised-metabolite candidates. In total, significantly altered features included features putatively assigned to 22 specialised metabolites, including actinorhodins, undecylprodigiosin, germicidins, geosmin, albaflavenone, melanin, flaviolin and desferrioxamine. The sco1897::Tn5 mutant and the strain overexpressing sco1900 exhibited high intracellular spore phosphate contents and extensive repression of specialised-metabolite production. Overexpression of the complete sco1898–1901 region did not significantly alter intracellular spore phosphate content but produced the largest number of increased specialised-metabolite features among the engineered strains. Notably, specialised metabolites that are normally detected at low abundance under standard laboratory conditions, such as albaflavenone, melanin and flaviolin, increased in particular genetic backgrounds. Conclusions Engineering the sco1897–sco1901 region affects both intracellular spore phosphate homeostasis and specialised metabolism in Streptomyces coelicolor , altering the abundance of features associated with at least 22 specialised metabolites. Although our results do not establish a simple causal relationship between intracellular spore phosphate levels and the observed metabolomic changes, they reveal the sco1897–sco1901 region as a promising target for metabolic engineering. Manipulation of this region may therefore provide a strategy for modulating specialised-metabolite production and potentially facilitating access to poorly expressed biosynthetic pathways in Streptomyces .