海洋シアノバクテリアにおける細胞内細菌共生体によるパゴアミドAの環境制御生産

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.