LCMS-Metabolomic Profiling and Genome Mining of Delftia lacustris DSM 21246 Revealed Lipophilic Delftibactin Metallophores

Abstract

Bacteria have evolved various strategies to combat heavy metal stress, including the secretion of small molecules, known as metallophores. These molecules hold a potential role in the mitigation of toxic metal contamination from the environment (bioremediation). Herein, we employed combined comparative metabolomic and genomic analyses to study the metallophores excreted by Delftia lacustris DSM 21246. LCMS-metabolomic analysis of this bacterium cultured under iron limitation led to a suite of lipophilic metallophores exclusively secreted in response to iron starvation. Additionally, we conducted genome sequencing of the DSM 21246 strain using nanopore sequencing technology and employed antiSMASH to mine the genome, leading to the identification of a biosynthetic gene cluster (BGC) matching the known BGC responsible for delftibactin A production. The isolated suite of amphiphilic metallophores, termed delftibactins C–F (1–4), was characterized using various chromatographic, spectroscopic, and bioinformatic techniques. The planar structure of these compounds was elucidated through 1D and 2D NMR analyses, as well as LCMS/MS-based fragmentation studies. Notably, their structures differed from previously known delftibactins due to the presence of a lipid tail. Marfey’s and bioinformatic analyses were employed to determine the absolute configuration of the peptide scaffold. Delftibactin A, a previously identified metallophore, has exhibited a gold biomineralizing property; compound 1 was tested for and also demonstrated this property.