Cytosolic copper is a major modulator of germination, development and secondary metabolism in Streptomyces coelicolor

Abstract

Streptomycetes are important biotechnological bacteria with complex differentiation. Copper is a well-known positive regulator of differentiation and antibiotic production. However, the specific mechanisms buffering cytosolic copper and the biochemical pathways modulated by copper remain poorly understood. Here, we developed a new methodology to quantify cytosolic copper in single spores which allowed us to propose that cytosolic copper modulates asynchrony of germination. We also characterised the SCO2730/2731 copper chaperone/P-type ATPase export system. A Streptomyces coelicolor strain mutated in SCO2730/2731 shows an important delay in germination, growth and sporulation. Secondary metabolism is heavily enhanced in the mutant which is activating the production of some specific secondary metabolites during its whole developmental cycle, including germination, the exponential growth phase and the stationary stage. Forty per cent of the S. coelicolor secondary metabolite pathways, are activated in the mutant, including several predicted pathways never observed in the lab (cryptic pathways). Cytosolic copper is precisely regulated and has a pleiotropic effect in gene expression. The only way that we know to achieve the optimal concentration for secondary metabolism activation, is the mutagenesis of SCO2730/2731. The SCO2730/2731 genes are highly conserved. Their inactivation in industrial streptomycetes may contribute to enhance bioactive compound discovery and production.

Structural and biochemical analysis of a phosin fromStreptomyces chartreusisreveals a combined polyphosphate‐ and metal‐binding fold

“…In Streptomyces , considerable variations in the cytoplasmic Cu 2+ concentration accompany development and strongly influence germination, differentiation and antibiotic synthesis . Consistent with these key regulatory roles, Cu 2+ levels are precisely controlled by means of a dedicated import and export machinery that includes a recently discovered chalkophore . It is conceivable that PptA acts as a sensor or modifier of the intracellular Cu 2+ concentration, while simultaneously measuring or affecting polyphosphate availability.…”

A two-component system gene SACE_0101 regulates copper homeostasis in Saccharopolyspora erythraea

“…For instance, TCS CopRS is closely related to the regulation of heavy metal copper ions in several bacteria. González-Quiñónez et al (2019) proposed a model describing the relationship between cytosolic copper and Streptomyces morphogenesis. The model suggests that copper is restricted to the differentiation (aerial mycelium and sporulation) and secondary metabolism while the vegetative growth proceeds even under a strongly limited cytosolic copper concentration.…”

The novel ECF56 SigG1-RsfG system modulates morphological differentiation and metal-ion homeostasis in Streptomyces tsukubaensis

“…Together with a disrupted iron balance, we show that strains defective in sigG1 were significantly more sensitive to exogenous copper than the wild-type. The mechanisms controlling copper uptake or secretion in Streptomyces species were recently identified 58 – 61 . The function of the product of STSU_32197 remains unknown since no clear homologues were identified for this protein.…”