Publications by authors named "Manja M Severinsen"

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Cyclic, Hydrophobic Hexapeptide Fusahexin Is the Product of a Nonribosomal Peptide Synthetase in .

J Nat Prod 2021 08 22;84(8):2070-2080. Epub 2021 Jul 22.

Department of Chemistry and Bioscience, Aalborg University, Frederik Bajers Vej 7H, DK-9220 Aalborg, Denmark.

The plant pathogenic fungus is known to produce a wide array of secondary metabolites during plant infection. This includes several nonribosomal peptides. Recently, the fusaoctaxin (/9) and gramilin () gene clusters were shown to be induced by host interactions. To widen our understanding of this important pathogen, we investigated the involvement of the gene cluster during infection and oxidative and osmotic stress. Overexpression of led to the discovery of a new cyclic hexapeptide, fusahexin (), with the amino acid sequence cyclo-(d-Ala-l-Leu-d--Thr-l-Pro-d-Leu-l-Leu). The structural analyses revealed an unusual ether bond between a proline C to C of the preceding threonine resulting in an oxazine ring system. The comparative genomic analyses showed that the small gene cluster only encodes an ABC transporter in addition to the five-module nonribosomal peptide synthetase (NRPS). Based on the structure of fusahexin and the domain architecture of , we propose a biosynthetic model in which the terminal module is used to incorporate two leucine units. So far, iterative use of NRPS modules has primarily been described for siderophore synthetases, which makes a rare example of a fungal nonsiderophore NRPS with distinct iterative module usage.
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http://dx.doi.org/10.1021/acs.jnatprod.0c00947DOI Listing
August 2021
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