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Biosynthesis of novel desferrioxamine derivatives requires unprecedented crosstalk between separate NRPS-independent siderophore pathways

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Su,  Li
Max Planck Institute for Terrestrial Microbiology, Max Planck Society;

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Citation

Su, L., Souaibou, Y., Hôtel, L., Paris, C., Weissman, K. J., & Aigle, B. (2023). Biosynthesis of novel desferrioxamine derivatives requires unprecedented crosstalk between separate NRPS-independent siderophore pathways. bioRxiv: the preprint server for biology, 2023.07.28.551008.


Cite as: https://hdl.handle.net/21.11116/0000-000D-8390-B
Abstract
Iron is essential to many biological processes, but its poor solubility in aerobic environments restricts its bioavailability. To overcome this limitation, bacteria have evolved a variety of strategies, including the production and secretion of iron-chelating siderophores. Here, we describe the discovery of four series of siderophores from Streptomyces ambofaciens ATCC23877, three of which are unprecedented. MS/MS-based molecular networking revealed that one of these series corresponds to acylated desferrioxamines (acyl-DFOs) recently identified from S. coelicolor. The remaining sets include unprecedented tetra- and penta-hydroxamate acyl-DFO derivatives, all of which incorporate a previously undescribed building block. Stable isotope labeling and gene deletion experiments provide evidence that biosynthesis of the acyl-DFO congeners requires unprecedented crosstalk between two separate NRPS-independent siderophore (NIS) pathways in the producing organism. The new derivatives, whose biological role(s) remain to be elucidated, not only illustrate the unanticipated biosynthetic potential of S. ambofaciens, but have interest in immuno-PET imaging applications.