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Elucidating the molecular programming of a nonlinear non-ribosomal peptide synthetase responsible for fungal siderophore biosynthesis
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Jenner, Matthew, Hai, Yang, Nguyen, Hong H., Passmore, Munro, Skyrud, Will, Kim, Junyong, Garg, Neil K., Zhang, Wenjun, Ogorzalek Loo, Rachel R. and Tang, Yi (2023) Elucidating the molecular programming of a nonlinear non-ribosomal peptide synthetase responsible for fungal siderophore biosynthesis. Nature Communications, 14 (1). 2832. doi:10.1038/s41467-023-38484-8 ISSN 2041-1723.
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WRAP-elucidating-molecular-programming-nonlinear-non-ribosomal-peptide-synthetase-responsible-fungal-siderophore-biosynthesis-Jenner-2023.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (1694Kb) | Preview |
Official URL: http://dx.doi.org/10.1038/s41467-023-38484-8
Abstract
Siderophores belonging to the ferrichrome family are essential for the viability of fungal species and play a key role for virulence of numerous pathogenic fungi. Despite their biological significance, our understanding of how these iron-chelating cyclic hexapeptides are assembled by non-ribosomal peptide synthetase (NRPS) enzymes remains poorly understood, primarily due to the nonlinearity exhibited by the domain architecture. Herein, we report the biochemical characterization of the SidC NRPS, responsible for construction of the intracellular siderophore ferricrocin. In vitro reconstitution of purified SidC reveals its ability to produce ferricrocin and its structural variant, ferrichrome. Application of intact protein mass spectrometry uncovers several non-canonical events during peptidyl siderophore biosynthesis, including inter-modular loading of amino acid substrates and an adenylation domain capable of poly-amide bond formation. This work expands the scope of NRPS programming, allows biosynthetic assignment of ferrichrome NRPSs, and sets the stage for reprogramming towards novel hydroxamate scaffolds.
Item Type: | Journal Article | ||||||||||||||||||||||||||||||||||||
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Subjects: | Q Science > QD Chemistry Q Science > QP Physiology Q Science > QR Microbiology R Medicine > RM Therapeutics. Pharmacology |
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Chemistry | ||||||||||||||||||||||||||||||||||||
Library of Congress Subject Headings (LCSH): | Siderophores, Iron chelates , Peptides -- Synthesis, Iron -- Physiological transport, Microbial metabolism, Mass spectrometry | ||||||||||||||||||||||||||||||||||||
Journal or Publication Title: | Nature Communications | ||||||||||||||||||||||||||||||||||||
Publisher: | Nature Publishing Group | ||||||||||||||||||||||||||||||||||||
ISSN: | 2041-1723 | ||||||||||||||||||||||||||||||||||||
Official Date: | 17 May 2023 | ||||||||||||||||||||||||||||||||||||
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Volume: | 14 | ||||||||||||||||||||||||||||||||||||
Number: | 1 | ||||||||||||||||||||||||||||||||||||
Article Number: | 2832 | ||||||||||||||||||||||||||||||||||||
DOI: | 10.1038/s41467-023-38484-8 | ||||||||||||||||||||||||||||||||||||
Status: | Peer Reviewed | ||||||||||||||||||||||||||||||||||||
Publication Status: | Published | ||||||||||||||||||||||||||||||||||||
Access rights to Published version: | Open Access (Creative Commons) | ||||||||||||||||||||||||||||||||||||
Date of first compliant deposit: | 12 December 2023 | ||||||||||||||||||||||||||||||||||||
Date of first compliant Open Access: | 12 December 2023 | ||||||||||||||||||||||||||||||||||||
RIOXX Funder/Project Grant: |
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