Morphological development and cytochrome c oxidase activity in Streptomyces lividans are dependent on the action of a copper bound Sco protein

Abstract

Copper has an important role in the life cycle of many streptomycetes, stimulating the developmental switch between vegetative mycelium and aerial hyphae concomitant with the production of antibiotics. In streptomycetes, a gene encoding for a putative Sco-like protein has been identified and is part of an operon that contains two other genes predicted to handle cellular copper. We report on the Sco-like protein from Streptomyces lividans (ScoSl) and present a series of experiments that firmly establish a role for ScoSl as a copper metallochaperone as opposed to a role as a thiol-disulphide reductase that has been assigned to other bacterial Sco proteins. Under low copper concentrations, a Δsco mutant in S. lividans displays two phenotypes; the development switch between vegetative mycelium and aerial hyphae stalls and cytochrome c oxidase (CcO) activity is significantly decreased. At elevated copper levels, the development and CcO activity in the Δsco mutant are restored to wild-type levels and are thus independent of ScoSl. A CcO knockout reveals that morphological development is independent of CcO activity leading us to suggest that ScoSl has at least two targets in S. lividans. We establish that one ScoSl target is the dinuclear CuA domain of CcO and it is the cupric form of ScoSl that is functionally active. The mechanism of cupric ion capture by ScoSl has been investigated, and an important role for a conserved His residue is identified.

The Genome Sequence of Streptomyces lividans 66 Reveals a Novel tRNA-Dependent Peptide Biosynthetic System within a Metal-Related Genomic Island

“…Interestingly, the duplicate ars operon is physically linked to a polyketide biosynthetic gene cluster (SLI1088–SLI1103) that is conserved in M145 and in S. coelicoflavus . Finally, other copper-related genes could be found within SLI1047–SLI1077, including two multi-copper oxidases (SLI1053 and SLI1071); extra copies of copZ and copA (SLI1063–SLI1064); and a paralog (SLI1067) of the previously characterized SLI4214 copper metallochaperone, or Sco1, involved in developmental switch and cytochrome c oxidase activity (Blundell et al 2013) (fig. 2).…”

Oxygen-Dependent Control of Respiratory Nitrate Reduction in Mycelium of Streptomyces coelicolor A3(2)

“…These bacteria are reliant on oxygen for growth and undergo a complex life cycle that includes growth as a substrate mycelium, followed by the development of aerial hyphae and the production of spores. While many early studies focused on the regulation of primary metabolism (2), comparatively few studies have addressed the regulation of respiration in Streptomyces (3)(4)(5) or what has been referred to as the "anaerobic paradox" (6). According to this paradox, although streptomycetes are unable to grow in the absence of oxygen, their genome nevertheless encodes enzymes whose products are associated with anaerobic metabolism (6).…”

Heterogeneity in the Histidine-brace Copper Coordination Sphere in Auxiliary Activity Family 10 (AA10) Lytic Polysaccharide Monooxygenases

“…Recent studies in S. lividans have identified an extracellular copper-trafficking pathway involving two copper chaperone proteins (Sco and ECuC) (34,35) and a DyP-type heme peroxidase (DtpA) (36) that are all required to facilitate GlxA maturation (i.e. copper-loading and subsequent Tyr-Cys cross-link formation (30)).…”