9NOM

Structure of the NIS synthetase NcdF from nocardichelin biosynthesis

Summary for 9NOM

• Entry DOI: 10.2210/pdb9nom/pdb
• Related: 9NIJ
• Descriptor: NcdF, a non-ribosomal independent siderophore synthetase, MALONATE ION (2 entities in total)
• Functional Keywords: nis synthetase, siderophore biosynthesis, nrps independent siderophores, ncdf, ligase
• Biological source: Nocardia carnea NBRC 14403
• Total number of polymer chains: 2
• Total formula weight: 137707.26

Authors

Fisk, M.B.,Gulick, A.M. (deposition date: 2025-03-10, release date: 2025-06-18, Last modification date: 2025-07-02)

Primary citation

Fisk, M.B.,Barrera Ramirez, J.,Merrick, C.E.,Wencewicz, T.A.,Gulick, A.M.
Identification and Characterization of the Biosynthesis of the Hybrid NRPS-NIS Siderophore Nocardichelin.
Acs Chem.Biol., 20:1435-1446, 2025

PubMed Abstract: Bacteria cope with the limitation of iron by producing siderophores, small molecules they export that have high affinity for iron. Once complexed, the ferric siderophore is transported into the cell through specialized receptors allowing the iron to be released and used in a variety of biological processes. Many peptide siderophores that use catechol, phenolate, or oxazoline/thiazoline groups to coordinate iron are produced by a family of enzymes called nonribosomal peptide synthetases (NRPSs). Alternately, a smaller family of NRPS-independent siderophores (NISs) is produced by a different biosynthetic strategy. The NIS pathways employ one or more NIS synthetases that combine an amine commonly harboring a hydroxamate with a carboxylate substrate. Discovered in 2007 in an uncharacterized species, a siderophore called nocardichelin was identified and chemically characterized that contained features of both NIS and NRPS siderophores. Nocardichelin contains an -salicyloxazoline moiety, predicted to be built by a modular NRPS, and a dihydroxamate containing -hydroxy--succinylcadaverine and -hydroxy--tetradecenoylcadaverine groups. To explore this potential hybrid NRPS/NIS, we identified a biosynthetic gene cluster in containing 13 enzymes and four proteins involved in transport. We have functionally characterized four of the enzymes for their activity and substrate specificity and further solved the structures of two enzymes. We present our discovery and initial characterization of this cluster, describe remaining questions for elucidation of the unusual siderophore, and discuss the potential for use in downstream biocatalytic applications.

PubMed: 40479602
DOI: 10.1021/acschembio.5c00286

Experimental method

X-RAY DIFFRACTION (2.87 Å)