Fatuamide A, a Hybrid PKS/NRPS Metallophore from a Leptolyngbya sp. Marine Cyanobacterium Collected in American Samoa

Type : ACL
Nature : Production scientifique
Au bénéfice du Laboratoire : Oui
Statut de publication : Publié
Année de publication : 2025
Auteurs (16) : ALEXANDER Kelsey,l NAMAN C,benjamin IWASAKI Arihiro MANGONI Alfonso LEAO Tiago REHER Raphael PETRAS Daniel KIM Hyunwoo TERNON Eva CARO-DIAZ Eduardo,j,e GLUKHOV Evgenia MITREVSKA Jana,a AVALON Nicole,e DUGGAN Brendan,m GERWICK Lena GERWICK William,h
Revue scientifique : Journal of Natural Products
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DOI : 10.1021/acs.jnatprod.4c01051
URL : https://doi.org/10.1021/acs.jnatprod.4c01051
Abstract : A structurally novel metabolite, fatuamide A (1), was discovered from a laboratory cultured strain of the marine cyanobacterium Leptolyngbya sp., collected from Faga’itua Bay, American Samoa. A bioassay-guided approach using NCI-H460 human lung cancer cells directed the isolation of fatuamide A, which was obtained from the most cytotoxic fraction. The planar structure of fatuamide A was elucidated by integrated NMR and MS/MS analysis, and a combination of bioinformatic and computational approaches was used to deduce the absolute configuration at its eight stereocenters. A putative hybrid PKS/NRPS biosynthetic gene cluster responsible for fatuamide A production was identified from the sequenced genomic DNA of the cultured cyanobacterium. The biosynthetic gene cluster possessed elements that suggested fatuamide A binds metals, and this metallophore property was demonstrated by native metabolomics and indicated a preference for binding copper. The producing strain was found to be highly resistant to toxicity from elevated copper concentrations in culture media.
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Commentaire : doi: 10.1021/acs.jnatprod.4c01051
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Citation :
Alexander KL, Naman CB, Iwasaki A, Mangoni A, Leao T, Reher R, Petras D, Kim H, Ternon E, Caro-Diaz EJE, Glukhov E, Mitrevska JA, Avalon NE, Duggan BM, Gerwick L, Gerwick WH (2025) Fatuamide A, a Hybrid PKS/NRPS Metallophore from a Leptolyngbya sp. Marine Cyanobacterium Collected in American Samoa. J Nat Prod | doi: 10.1021/acs.jnatprod.4c01051