Complete Structure of Delftibactin A and Its Function in Reductive Formation of Gold Nanoparticles

Delftia acidovorans is a rare bacterium that colonizes the surface of gold nuggets and secretes a peptidic natural product, delftibactin A (1). Compound 1 strongly chelates and readily transforms soluble and toxic Au(III) ions into inert and nontoxic gold nanoparticles, allowing the bacteria to survive metal stress from Au(III) ions. This reductive function of 1 is not shared by any other known natural products, while its stereochemistry and mode of action have remained unclear. Here, we report the first total synthesis, structural elucidation, and functional analysis of 1. First, we enabled the collective solid-phase total synthesis of 16 possible diastereomers of 1. Second, the complete structure of 1 was determined by a detailed NMR analysis of these diastereomers. Third, we uncovered the evolutionarily optimized nature of the stereochemistry of 1 for facile Au(III) reduction and elucidated the novel reaction mechanism of 1. As a result, we identified the precise roles of key structural elements involved in the unprecedented activity of 1, providing a valuable foundation for designing new molecules aimed at generating customized gold nanoparticles and mitigating toxic Au(III) ions from the environment.