Genome-guided natural product discovery from an octopus-derived Pseudoalteromonas species

Members of the genus Pseudoalteromonas have significant ecological importance. They are commonly found in association with diverse eukaryotic organisms and are known to produce many biologically active natural products. Despite being a widely studied genus, many of the biosynthesis pathways that give rise to this complement of structurally diverse metabolites produced by Pseudoalteromonas spp. are hitherto unknown.

The genetics underpinning natural product structures and their biosynthesis pathways are so well understood that “Genome Mining” is now a major avenue toward natural products discovery and elucidation of biosynthesis pathways. The reduction in cost of sequencing microbial genomes resulting from new technologies coupled with more powerful bioinformatic tools has expedited the discovery of novel natural products and their biosynthesis pathways.

The focus of our investigation, Pseudoalteromonas HM-SA03, which was isolated from a blue ringed octopus belonging to the Hapalochlaena genus, is rich in natural product biosynthesis coding genes indicating unrealised biosynthetic potential. We used bioinformatics based approaches to assemble seven NRPS or PKS biosynthetic gene clusters from HM-SA03, predict their natural product structures, and guide the discovery of these metabolites.

This study identified biosynthesis gene clusters responsible for the assembly of the alterochromides, alteramides and a pseudoalterobactin-like compound in addition to four gene clusters whose similar products have not been reported. Using both molecular and analytical methods we have confirmed the production of some of these compounds or their analogues. The abundance of NRPS and PKS gene clusters in Pseudoalteromonas has confirmed the unrealised natural product biosynthetic potential of this genus.