Abstract
The filamentous bacterium Streptomyces lividans depends on the radical copper oxidase GlxA for the formation of reproductive aerial structures and, in liquid environments, for the formation of pellets. Incorporation of copper into the active site is essential for the formation of a cross-linked tyrosyl-cysteine cofactor, which is needed for enzymatic activity. In this study, we show a crucial link between GlxA maturation and a group of copper-related proteins including the chaperone Sco and a novel DyP-type peroxidase hereinafter called DtpA. Under copper-limiting conditions, the sco and dtpA deletion mutants are blocked in aerial growth and pellet formation, similarly to a glxA mutant. Western blot analysis showed that GlxA maturation is perturbed in the sco and dtpA mutants, but both maturation and morphology can by rescued by increasing the bioavailability of copper. DtpA acts as a peroxidase in the presence of GlxA and is a substrate for the twin-arginine translocation (Tat) translocation pathway. In agreement, the maturation status of GlxA is also perturbed in tat mutants, which can be compensated for by the addition of copper, thereby partially restoring their morphological defects. Our data support a model wherein a copper-trafficking pathway and Tat-dependent secretion of DtpA link to the GlxA-dependent morphogenesis pathway.
Highlights
Streptomycetes are multicellular bacteria with a complex developmental life cycle
Following the germination of spores, a network of interconnected filaments is established, which is called a vegetative mycelium. This mycelium feeds on nutrients in the soil until they become depleted. This nutrient scarcity triggers the onset of a developmental programme, leading to the lysis of the vegetative mycelium, and the formation of aerial hyphae that erect from the colony surface into the air, and which gives the colony a white, fluffy appearance [1,2]
Morphological differentiation in streptomycetes is a complex process that depends on environmental conditions and extensive extracellular signalling between hyphae [1,11,54]
Summary
Streptomycetes are multicellular bacteria with a complex developmental life cycle. Following the germination of spores, a network of interconnected filaments is established, which is called a vegetative mycelium. This mycelium feeds on nutrients in the soil until they become depleted This nutrient scarcity triggers the onset of a developmental programme, leading to the lysis of the vegetative mycelium, and the formation of aerial hyphae that erect from the colony surface into the air, and which gives the colony a white, fluffy appearance [1,2]. Differentiation of these reproductive structures leads to the synchronous production of millions of grey-pigmented spores that disperse. At the onset of aerial mycelium formation, streptomycetes produce a richness of secondary metabolites, including numerous antibiotics, anti-tumour compounds and anthelmintic agents that make them of interest for pharmaceutical purposes [3,4]. Owing to their competence to directly secrete proteins in the culture broth, streptomycetes hold promise as hosts for the heterologous production of enzymes [5,6]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
