A <i>Pseudoalteromonas</i> Clade with Remarkable Biosynthetic Potential

Abstract

<i>Pseudoalteromonas</i> species produce a diverse range of biologically active compounds, including those biosynthesized by nonribosomal peptide synthetases (NRPSs) and polyketide synthases (PKSs). Here, we report the biochemical and genomic analysis of <i>Pseudoalteromonas</i> sp. strain HM-SA03, isolated from the blue-ringed octopus, <i>Hapalochlaena</i> sp. Genome mining for secondary metabolite pathways revealed seven putative NRPS/PKS biosynthesis gene clusters, including those for the biosynthesis of alterochromides, pseudoalterobactins, alteramides, and four novel compounds. Among these was a novel siderophore biosynthesis gene cluster with unprecedented architecture (NRPS-PKS-NRPS-PKS-NRPS-PKS-NRPS). Alterochromide production in HM-SA03 was also confirmed by liquid chromatography-mass spectrometry. An investigation of the biosynthetic potential of 42 publicly available <i>Pseudoalteromonas</i> genomes indicated that some of these gene clusters are distributed throughout the genus. Through the phylogenetic analysis, a particular subset of strains formed a clade with extraordinary biosynthetic potential, with an average density of 10 biosynthesis gene clusters per genome. In contrast, the majority of <i>Pseudoalteromonas</i> strains outside this clade contained an average of three clusters encoding complex biosynthesis. These results highlight the underexplored potential of <i>Pseudoalteromonas</i> as a source of new natural products.<b>IMPORTANCE</b> This study demonstrates that the <i>Pseudoalteromonas</i> strain HM-SA03, isolated from the venomous blue-ringed octopus, <i>Hapalochalaena</i> sp., is a biosynthetically talented organism, capable of producing alterochromides and potentially six other specialized metabolites. We identified a pseudoalterobactin biosynthesis gene cluster and proposed a pathway for the production of the associated siderophore. A novel siderophore biosynthesis gene cluster with unprecedented architecture was also identified in the HM-SA03 genome. Finally, we demonstrated that HM-SA03 belongs to a phylogenetic clade of strains with extraordinary biosynthetic potential. While our results do not support a role of HM-SA03 in <i>Hapalochalaena</i> sp. venom (tetrodotoxin) production, they emphasize the untapped potential of <i>Pseudoalteromonas</i> as a source of novel natural products.