Comparative Binding Studies of the Chelators Methylolanthanin and Rhodopetrobactin B to Lanthanides and Ferric Iron

The question of lanthanide (Ln)-uptake in Ln-using bacteria has gained a lot of attention in recent years and the existence of specific Ln-binding metallophores, so-called lanthanophores, has been postulated. Here we investigate the recently isolated metallophore methylolanthanin (MLL), which was shown to be involved in Ln-metabolism of Methylobacterium extorquens AM1 along the structurally related siderophore rhodopetrobactin B (RPB B). We report the total synthesis of both chelators as well as Ln-binding investigations employing a multitude of spectroscopic methods. Compared to MLL, RPB B has a higher binding affinity for Fe3+. Unexpectedly, both metallophores seem to precipitate Lns under biologically relevant conditions (pH and concentration range). We used a combination of single-cell (sc)ICP MS and LC MS analysis of bacterial supernatant to investigate the Nd accumulation as well as MLL secretion under Fe limitation in M. extorquens AM1. Finally, we use ion mobility spectrometry-mass spectrometry (IMS-MS) and quantum chemical calculations to investigate the RPB B and MLL complexation in the gas phase with Fe3+ and all rare earth elements (except Pm). Our results challenge the classical siderophore-like Ln-uptake (via simple solubilisation) through MLL and underline again a potential complex interplay between Fe3+ and Ln3+ in microbial Ln-uptake.