Fatuamide A, a Hybrid PKS/NRPS Metallophore from a <i>Leptolyngbya</i> sp. Marine Cyanobacterium Collected in American Samoa
A structurally novel metabolite, fatuamide A (<b>1</b>), was discovered from a laboratory cultured strain of the marine cyanobacterium <i>Leptolyngbya</i> 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.
Authors
- Tiago Leão (ORCID: https://orcid.org/0000-0003-1034-9153)
- Daniel Petras (ORCID: https://orcid.org/0000-0002-6561-3022)
- Alfonso Mangoni (ORCID: https://orcid.org/0000-0003-3910-6518)
- Brendan M. Duggan (ORCID: https://orcid.org/0000-0002-7034-8374)
- Evgenia Glukhov (ORCID: https://orcid.org/0000-0001-6513-9909)
- Eva Ternon (ORCID: https://orcid.org/0000-0002-7211-3157)
- Kelsey L. Alexander (ORCID: https://orcid.org/0000-0002-4727-5349)
- C. Benjamin Naman (ORCID: https://orcid.org/0000-0002-4361-506X)
- Lena Gerwick (ORCID: https://orcid.org/0000-0001-6108-9000)
- Eduardo J. E. Caro‐Diaz (ORCID: https://orcid.org/0000-0002-2049-6248)
- Nicole E. Avalon (ORCID: https://orcid.org/0000-0003-3588-892X)
- Raphael Reher (ORCID: https://orcid.org/0000-0002-5858-1173)
- William H. Gerwick (ORCID: https://orcid.org/0000-0003-1403-4458)
- Arihiro Iwasaki (ORCID: https://orcid.org/0000-0002-3775-5066)
- Jana Mitrevska (ORCID: https://orcid.org/0009-0003-7600-7057)
- Hyun Woo Kim (ORCID: https://orcid.org/0000-0003-2473-8360)
Institutions
- University of California, Riverside (US)
- Centre National de la Recherche Scientifique (FR)
- Scripps Institution of Oceanography (US)
- University of Puerto Rico, Medical Sciences Campus (PR)
- Philipps University of Marburg (DE)
- Keio University (JP)
- Dongguk University (KR)
- Department of Environment and Conservation (CA)
- University of California San Diego (US)
- Sorbonne Université (FR)
- Czech Academy of Sciences, Institute of Microbiology (CZ)
- Department of Conservation (NZ)
- Laboratoire d’Océanographie de Villefranche (FR)
- University of Naples Federico II (IT)
- University of Tübingen (DE)
- Universidade Estadual Paulista (Unesp) (BR)
Publication Details
- Journal
- Journal of Natural Products
- Published
- 2025-01-29
- DOI
- https://doi.org/10.1021/acs.jnatprod.4c01051
- Citations
- 6
- Primary Topic
- Microbial Natural Products and Biosynthesis
- Type
- article
- Field-Weighted Citation Impact
- 8.37
Funders
- Deutsche Forschungsgemeinschaft
- National Institutes of Health
- University of California, San Diego
- National Cancer Institute
- National Institute of General Medical Sciences
- National Center for Complementary and Integrative Health