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Environmentally controlled production of pagoamide A in marine macroalgae by an intracellular bacterial symbiont
Liu, J.; Glukhov, E.; De Clerck, O.; Gerwick, W.H.; Donia, M.S. (2026). Environmentally controlled production of pagoamide A in marine macroalgae by an intracellular bacterial symbiont. Curr. Biol. 36(1): 63-79.E6. https://dx.doi.org/10.1016/j.cub.2025.11.023
In: Current Biology. Cell Press: London. ISSN 0960-9822; e-ISSN 1879-0445, more
Peer reviewed article  

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  • Liu, J.
  • Glukhov, E.
  • De Clerck, O., more
  • Gerwick, W.H.
  • Donia, M.S.

Abstract
    Marine algae are a rich source of diverse molecules, most of which are thought to be produced by the alga itself. We recently reported the discovery of pagoamide A from a cultured marine macroalga collected from American Samoa. Here, we found that the production of pagoamide A is conditional upon environmental temperature. Using comparative metagenomic, metatranscriptomic, and metabolomic analyses of algal cultures, we identified a nonribosomal peptide synthetase biosynthetic gene cluster (NRPS BGC) in the algal microbiome that varies in abundance between producing and non-producing conditions and whose architecture and biosynthetic logic match pagoamide A (named pag). pag belongs to a bacterium that we named “Candidatus Bryopsidiphilus pagoamidifaciens BP1,” a new genus in the family Amoebophilaceae and a relative of amoeba, arthropod, and nematode endosymbionts. Ca. B. pagoamidifaciens lives intracellularly in its Bryopsis sp. algal host, harbors a reduced genome (1.7 Mbp), has lost most genes essential for free living, and is enriched in genes containing eukaryotic domains. By quantitatively monitoring longitudinal algal cultures under varying conditions for 9 weeks, we found that the abundance of both Ca. B. pagoamidifaciens and pagoamide A undergoes dramatic fluctuations in response to temperature changes. Finally, we discovered three additional strains of Ca. B. pagoamidifaciens that vary in their NRPS BGCs and eukaryotic domain-containing genes from algal samples of diverse geographical origins. Our findings suggest that symbiont-derived production of algal molecules is more common than previously anticipated and provide a unique case of environmental control of both symbiont and chemical levels in marine algae.

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