SIDERITE: Unveiling Hidden Siderophore Diversity in the Chemical Space Through Digital Exploration

Abstract

Siderophores, a highly diverse family of secondary metabolites, play a crucial role in facilitating the acquisition of the essential iron. However, the current discovery of siderophore relies largely on manual approaches. In this work, we introduced SIDERTE, a digitized siderophore information database containing 822 siderophore records with 649 unique structures. Leveraging this digitalized dataset, we gained a systematic overview of siderophores by their clustering patterns in the chemical space. Building upon this, we developed a ligand-based method for predicting new iron-binding molecules. Applying this method to a commercial library, we experimentally confirmed that 40 out of the 48 molecules predicted as siderophore candidates possessed iron-binding abilities. Expanding our approach to the COCONUT natural product database, we predicted a staggering 3,199 siderophore candidates, showcasing remarkable structure diversity that are largely unexplored. Our study provides a valuable resource for accelerating the discovery of novel iron-binding molecules and advancing our understanding towards siderophores.

Siderophore Piracy Promotes Dynamical Coexistence in Microbial Community

“…In response to this iron deficiency, microbes produce and secrete siderophores, which are small molecules with a high affinity for iron. These siderophores bind to iron and are then taken up by membrane receptors 12,15 .There exists a diverse range of siderophores 16 . Interestingly, specific types of membrane receptors demonstrate selective recognition and uptake for particular types of siderophores 17,18 , similar to a lock-key system 19 .…”