Automated detection of metallophore biosynthesis reveals that metal-chelating non-ribosomal peptides are widespread, chemically diverse, and deeply rooted in bacterial evolution.

Automated detection of metallophore biosynthesis reveals that metal-chelating non-ribosomal peptides are widespread, chemically diverse, and deeply rooted in bacterial evolution.

Cyanobacteria are known for their rich secondary metabolome with a long history of research directed toward the industrial and pharmaceutical applications of their natural products. Cyanobacterial metallophores (metal-chelating molecules), however, are understudied relative to metallophores from other phyla despite evidence suggesting that genes for metallophore biosynthesis are well-represented in cyanobacterial genomes. Many of the characterized cyanobacterial metallophores are formed from hybrid biosynthetic pathways and feature mixed coordinating functional groups, leading to enhanced structural and functional diversity. The few characterized metallophore families have intriguing properties including promiscuity of metal binding, photoreactivity, and amphiphilicity that are yet to be fully explored. Research suggests that these compounds are ecologically relevant and could guide community dynamics by controlling the availability of iron, detoxifying copper, and allelopathically inhibiting certain organisms. Cyanobacterial metallophores also have potential in the fields of therapeutic design, bioremediation, technology, and agriculture. In the past five years, the number of characterized metallophores from cyanobacteria has doubled, pointing to the great promise for future discoveries.

Metals are essential trace elements for almost all organisms including bacteria. Yet, metals are toxic at high concentrations, requiring fine-tuned regulatory mechanisms to steer metal homeostasis ins...

Covering: up to 2025 Metallophores are metal-chelating natural products produced by microorganisms to scavenge essential metal ions in nutrient-limited environments. Among them, yersiniabactin-type…

Many bacteria secrete metallophores, low-molecular-weight organic compounds that bind ions with high selectivity and affinity, in order to access e...

Metal chelating small molecules (metallophores) play significant roles in microbial interactions and bacterial survival; however, current methods to identify metallophores are limited by low sensitivity, a lack of metal selectivity, and/or complicated data analysis. To overcome these limitations, we developed a novel approach for detecting metallophores in natural product extracts using ion mobility-coupled mass spectrometry (IM-MS). As a proof of concept, marine bacterial extracts containing known metallophores were analyzed by IM-MS with and without added metals, and the data were compared between conditions to identify metal-binding metabolites. Ions with changes in both mass and mobility were specific to metallophores, enabling their identification within these complex extracts. Additionally, we compared the use of direct infusion (DI) and liquid chromatography (LC) separation with IM-MS. For most samples, DI outperformed LC by minimizing the time required for data collection and simplifying analysis. However, for some samples, LC improved the detection of metallophores likely by reducing ion suppression. IM-MS was then used to identify 10 metallophores in an extract from a marine Micromonospora sp. Overall, incorporating IM-MS facilitated the rapid detection of metal-binding natural products in complex bacterial extracts through the comparison of mass and mobility data in the presence and absence of metals.

Metals are essential trace elements for almost all organisms including bacteria. Yet, metals are toxic at high concentrations, requiring fine-tuned regulatory mechanisms to steer metal homeostasis inside cells. In this primer, we explain how bacterial metallophores – small secreted secondary metabolites – act as gatekeepers by carefully orchestrating the scavenging and uptake of essential metals whilst preventing intracellular toxicity and keeping toxic metals outside the cell. We further introduce metallophore diversity together with main synthesis, secretion and uptake mechanisms. Finally, we show how secreted metallophores shape ecological interactions between bacteria and with eukaryotic organisms and how fundamental research on metallophores opens promising avenues for therapeutic and biotechnological applications.

Abstract. The importance of rare earth elements is increasingly recognized due to the increased demand for their mining and separation. This demand is driv

Microbial metallophores are low-molecular-weight chelating agents produced by microorganisms to acquire essential metal ions. Their biosynthesis, transport, and regulation involve complex processes, specialized enzymatic machinery, and intricate regulatory networks. This review examines the multifaceted roles of metallophores in microbial ecology and their potential applications in sustainable agriculture, emphasizing their key role in trace metal acquisition, nutrient cycling, and plant–microbe interactions. Furthermore, it explores the potential applications of metallophores in agriculture, bioremediation, and biotechnology, connecting their potential to the development of novel strategies for sustainable agriculture.

Cyanobacteria are known for their rich secondary metabolome with a long history of research directed toward the industrial and pharmaceutical applications of their natural products. Cyanobacterial met...