A Pseudoalteromonas Clade with Remarkable Biosynthetic Potential

Abstract

Pseudoalteromonas species produce a diverse range of biologically active compounds, including those biosynthesized by non-ribosomal peptide synthetases (NRPSs) and polyketide synthases (PKSs). Here we report the biochemical and genomic analysis of Pseudoalteromonas sp. HM-SA03, isolated from the blue-ringed octopus, Hapalochalaena 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 hitherto 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 Pseudoalteromonas genomes indicated that some of these gene clusters are distributed throughout the genus. Through phylogenetic analysis, a particular subset of strains formed a clade with extraordinary biosynthetic potential, with an average density of ten biosynthesis gene clusters per genome. In contrast, the majority of Pseudoalteromonas strains outside this clade contained an average of three clusters encoding complex biosynthesis. These results highlight the under-explored potential of Pseudoalteromonas as a source of new natural products. Importance This study demonstrates that the Pseudoalteromonas strain, HM-SA03, isolated from the venomous blue-ringed octopus, Hapalochalaena sp., is a biosynthetically talented organism, capable of producing alterochromides and potentially six other specialized metabolites. We have 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 have 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 Hapalochalaena sp. venom (tetrodotoxin) production, they emphasize the untapped potential of Pseudoalteromonas as a source of novel natural products.

Marine Sponge and Octocoral-Associated Bacteria Show Versatile Secondary Metabolite Biosynthesis Potential and Antimicrobial Activities against Human Pathogens

“…PARCl1 displayed moderate antibacterial activity and was also found to harbor multiple NRPS SM-BGCs. However, strain PARC11 is phylogenetically different from the SM-BGC-enriched Pseudoalteromonas clade described by Chau and colleagues [ 62 ]. In contrast, 14 other Pseudoalteromonas sp.…”

“…are versatile antimicrobial compound producers, with 69 antimicrobial compounds reported until 2016 [ 61 ]. More recently, a clade consisting of at least 19 Pseudoalteromonas members was reported by Chau and colleagues to possess large numbers of SM-BGCs (on average >10 SM-BGCs per genome), including SM-BGCs which produce polyketides, non-ribosomal peptides and RiPPs/bacteriocins [ 62 ]. In this study, Pseudoalteromonas sp.…”

“…In contrast, 14 other Pseudoalteromonas sp. strains of the “EcoTech-SPONGE” collection had >99% 16S rRNA gene similarity to the abovementioned SM-BGC-enriched Pseudoalteromonas [ 62 ] ( Table S10 ). These 14 Pseudoalteromonas strains may thus be a valuable target for future bioprospection studies, possibly also displaying a complex secondary metabolism.…”

“…S9: Overview on the gene cluster families (GCF) shown in Figure 5 B and details on the origin (isolate) and compound class contributing to each GCF. S10: Pairwise comparison of the 16S rRNA gene sequences of the 14 Pseudoalteromonas isolates from the “EcoTech-SPONGE” culture collection with those of the SM-BGC enriched Pseudoalteromonas clade reported in Chau et al, 2021 [ 62 ].…”

Draft Genome Sequences of 10 Bacteria from the Marine Pseudoalteromonas Group

“…Some Pseudoalteromonas species produce compounds that inhibit the fouling of marine surfaces by invertebrates and algae ( 2 ), while others stimulate the metamorphosis of tubeworms, urchins, and corals ( 3 ). Many pseudoalteromonads possess the ability to produce diverse specialized metabolites ( 4 – 6 ), providing an understudied resource for biotechnology.…”