Copper-chelating natural products

Bacteria and fungi produce natural products that coordinate copper for a variety of functions. Many copper-binding natural products function as copper-chelating metallophores, or chalkophores, that scavenge copper from the environment to meet cellular needs. By contrast, some compounds sequester toxic levels of environmental copper to protect the producing microorganism. These copper-binding compounds often have antimicrobial activities as well. In recent years, a number of new copper-coordinating natural products have been reported, including both ribosomally and non-ribosomally synthesized molecules. There have also been significant advances in understanding the biosynthesis of these and previously known copper chelators, leading to the discovery of new enzyme families. This review summarizes the recently discovered copper-binding natural products, their biosynthetic pathways, and their functions. By highlighting key biosynthetic enzymes, we hope to inspire the discovery of new copper-coordinating natural products that may be used as therapeutics and antimicrobial agents.