Chalkophores

Abstract

Copper-binding metallophores, or chalkophores, play a role in microbial copper homeostasis that is analogous to that of siderophores in iron homeostasis. The best-studied chalkophores are members of the methanobactin (Mbn) family—ribosomally produced, posttranslationally modified natural products first identified as copper chelators responsible for copper uptake in methane-oxidizing bacteria. To date, Mbns have been characterized exclusively in those species, but there is genomic evidence for their production in a much wider range of bacteria. This review addresses the current state of knowledge regarding the function, biosynthesis, transport, and regulation of Mbns. While the roles of several proteins in these processes are supported by substantial genetic and biochemical evidence, key aspects of Mbn manufacture, handling, and regulation remain unclear. In addition, other natural products that have been proposed to mediate copper uptake as well as metallophores that have biologically relevant roles involving copper binding, but not copper uptake, are discussed.

Cu Homeostasis in Bacteria: The Ins and Outs

“…Under metal-limiting conditions, most bacteria synthesize metallophores, which are organic compounds with high-metal affinity [ 88 , 89 , 117 ]. Upon their synthesis, the metallophores are exported to the extracellular environment, where they bind their specific metal.…”

“…The metal–metallophore complexes are subsequently imported back into the intracellular space for metal release. Chalkophores (chalko: Greek word for Cu) are Cu-binding metallophores [ 117 ], that are functionally comparable to the well-known siderophores and are synthesized in response to low iron availability [ 88 ]. Well-characterized chalkophores are methanobactins and yersiniabactin, which are described in this section ( Figure 3 ).…”

Native Electrospray-based Metabolomics Enables the Detection of Metal-binding Compounds

“…enterobactin) 2–4 , and carboxylates (i.e. rhizoferrin and aerobactin) 2–5 , while chalkophores such as methanobactins and SF2768 (a diisonitrile natural product) play the analogous role in binding cuprous copper (Cu + ) 6,7 , and a number of zincophores have also been recently elucidated 8–11 . In addition to small molecule ionophores that play a role in microbial metal transport and homeostasis, metals can also serve as cofactors essential for the function of other small molecules.…”

Biochemical pathway for the biosynthesis of the CuA center in bacterial cytochrome c oxidase

“…Quite advanced are also studies on copper acquisition in methanotrophic bacteria, which need Cu in supply of their methane monooxygenases. In addition, siderophore-like, small molecules for Cu chelationdubbed chalkophoreswere discovered as vehicles for Cu dissemination in these species [70]. Is the making of a B. diazoefficiens ScoIÁCu 2+ ÁCoxB complex exclusive or not?…”