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

Autor: 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., 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., Nguyen HH; Department of Chemistry and Biochemistry, University of California, Los Angeles, USA.; Transmed Co., Ltd., Ho Chi Minh City, Vietnam., Passmore M; Department of Chemistry, University of Warwick, Coventry, CV4 7AL, UK., Skyrud W; Department of Chemical and Biomolecular Engineering, University of California, Berkeley, USA.; Arzeda, 3421 Thorndyke Ave W, Seattle, WA 98119, USA., Kim J; Department of Chemistry and Biochemistry, University of California, Los Angeles, USA., Garg NK; Department of Chemistry and Biochemistry, University of California, Los Angeles, USA., Zhang W; Department of Chemical and Biomolecular Engineering, University of California, Berkeley, USA., Ogorzalek Loo RR; Department of Chemistry and Biochemistry, University of California, Los Angeles, USA., Tang Y; Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, USA.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 May 17; Vol. 14 (1), pp. 2832. Date of Electronic Publication: 2023 May 17.
DOI: 10.1038/s41467-023-38484-8
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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