Elucidating the molecular programming of a nonlinear non-ribosomal peptide synthetase responsible for fungal siderophore biosynthesis.

Siderophores / metabolism Ferrichrome / chemistry Iron / metabolism Peptide Synthases / metabolism

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
17 05 2023
Historique:
received: 18 10 2022
accepted: 25 04 2023
medline: 19 5 2023
pubmed: 18 5 2023
entrez: 17 5 2023
Statut: epublish

Résumé

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.

Identifiants

DOI: 10.1038/s41467-023-38484-8 PMID: 37198174 PMC: PMC10192304
pubmed: 37198174
doi: 10.1038/s41467-023-38484-8
pii: 10.1038/s41467-023-38484-8
pmc: PMC10192304
doi:

Substances chimiques

Siderophores 0
Ferrichrome 15630-64-5
non-ribosomal peptide synthase EC 6.3.2.-
Iron E1UOL152H7
Peptide Synthases EC 6.3.2.-

Types de publication

Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

2832

Subventions

Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/R012121/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/M017982/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/M01116X/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/W011247/1
Pays : United Kingdom
Organisme : NIGMS NIH HHS
ID : R35 GM118056
Pays : United States
Organisme : NCCIH NIH HHS
ID : DP2 AT009148
Pays : United States
Organisme : NCRR NIH HHS
ID : S10 RR025631
Pays : United States

Informations de copyright

© 2023. The Author(s).

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Auteurs

Matthew Jenner (M)

Department of Chemistry, University of Warwick, Coventry, CV4 7AL, UK. m.jenner@warwick.ac.uk.
Warwick Integrative Synthetic Biology Centre (WISB), University of Warwick, Coventry, CV4 7AL, UK. m.jenner@warwick.ac.uk.
ORCID: 0000-0003-2317-3011

Yang Hai (Y)

Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, USA. hai@chem.ucsb.edu.
Department of Chemistry and Biochemistry, University of California, Santa Barbara, USA. hai@chem.ucsb.edu.
ORCID: 0000-0002-2039-5367

Hong H Nguyen (HH)

Department of Chemistry and Biochemistry, University of California, Los Angeles, USA.
Transmed Co., Ltd., Ho Chi Minh City, Vietnam.

Munro Passmore (M)

Department of Chemistry, University of Warwick, Coventry, CV4 7AL, UK.

Will Skyrud (W)

Department of Chemical and Biomolecular Engineering, University of California, Berkeley, USA.
Arzeda, 3421 Thorndyke Ave W, Seattle, WA 98119, USA.

Junyong Kim (J)

Department of Chemistry and Biochemistry, University of California, Los Angeles, USA.

Neil K Garg (NK)

Department of Chemistry and Biochemistry, University of California, Los Angeles, USA.
ORCID: 0000-0002-7793-2629

Wenjun Zhang (W)

Department of Chemical and Biomolecular Engineering, University of California, Berkeley, USA.
ORCID: 0000-0001-9348-972X

Rachel R Ogorzalek Loo (RR)

Department of Chemistry and Biochemistry, University of California, Los Angeles, USA.
ORCID: 0000-0002-0580-2833

Yi Tang (Y)

Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, USA.
ORCID: 0000-0003-1597-0141

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Classifications MeSH

questionsmedicales.fr › Actions chimiques et utilisations › Utilisations spécialisées de produits chimiques › Agents séquestrants › Chélateurs › Agents chélateurs du fer › Sidérophores › Elucidating the molecular programming of a...
questionsmedicales.fr › Acides aminés, peptides et protéines › Peptides › Peptides cycliques › Ferrichrome › Elucidating the molecular programming of a...
questionsmedicales.fr › Produits chimiques inorganiques › Métaux › Métaux lourds › Fer › Elucidating the molecular programming of a...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Ligases › Carbon-nitrogen ligases › Amino-acid ligases › Elucidating the molecular programming of a...