Identification of Secondary Metabolite Gene Clusters in the Pseudovibrio Genus Reveals Encouraging Biosynthetic Potential toward the Production of Novel Bioactive Compounds

Abstract

Increased incidences of antimicrobial resistance and the emergence of pan-resistant ‘superbugs’ have provoked an extreme sense of urgency amongst researchers focusing on the discovery of potentially novel antimicrobial compounds. A strategic shift in focus from the terrestrial to the marine environment has resulted in the discovery of a wide variety of structurally and functionally diverse bioactive compounds from numerous marine sources, including sponges. Bacteria found in close association with sponges and other marine invertebrates have recently gained much attention as potential sources of many of these novel bioactive compounds. Members of the genus Pseudovibrio are one such group of organisms. In this study, we interrogate the genomes of 21 Pseudovibrio strains isolated from a variety of marine sources, for the presence, diversity and distribution of biosynthetic gene clusters (BGCs). We expand on results obtained from antiSMASH analysis to demonstrate the similarity between the Pseudovibrio-related BGCs and those characterized in other bacteria and corroborate our findings with phylogenetic analysis. We assess how domain organization of the most abundant type of BGCs present among the isolates (Non-ribosomal peptide synthetases and Polyketide synthases) may influence the diversity of compounds produced by these organisms and highlight for the first time the potential for novel compound production from this genus of bacteria, using a genome guided approach.

Ecology and Biotechnological Potential of Bacteria Belonging to the Genus Pseudovibrio

“…These values remain below the biosynthetic ability of the most gifted actinomycetes but are comparable with those of other relevant bioactive molecule producers, such as bacteria belonging to the Bacillaceae, Oxalobacteraceae, and Pseudoalteromonadaceae families (Table S2B) (95)(96)(97). Interestingly, even closely related and coisolated Pseudovibrio strains showed variation in their BGCs, indicating both different mechanisms potentially used for the interaction with the host and its microbiome and the diversity of natural products potentially produced (42,47). Chemical characterization of secondary metabolites is a slow process, but it is important to keep in mind that often the standard procedures used for the cultivation of these strains might limit the expression of their BGCs (98).…”

“…Supporting the widespread experimental bioactivity, recent genomic data showed the diversity of secondary metabolite biosynthetic gene clusters (BGCs) in Pseudovibrio genomes (42,47,48,75). Among others, BGCs for terpene, polyketide synthase (PKS), nonribosomal peptide synthetase (NRPS), bacteriocin, and homoserine lactone were identified.…”

“…In order to gain an overview of the environmental distribution and abundance of Pseudovibrio spp., here, all available 16S rRNA amplicon data sets from the Sequence Read Archive (SRA; as of 31 December 2017) were interrogated for the presence of sequences assigned to this genus. Forty-nine publicly available Pseudovibrio genome assemblies were annotated as previously described, and 16S rRNA genes were collected and clustered using VSEARCH version 1.1.1 with a 99% identity threshold (42,43). The 14 representative sequences (centroids) were then submitted to the Integrated Microbial Next Generation Sequencing platform (IMNGS), using a genus threshold of 95% (44).…”

“…Among others, BGCs for terpene, polyketide synthase (PKS), nonribosomal peptide synthetase (NRPS), bacteriocin, and homoserine lactone were identified. Based on the data of Naughton et al (42) and on the information found in the Integrated Microbial Genomes portal (94), here it was calculated that in Pseudovibrio spp., 3.2% Ϯ 1.3% of the whole genome and 3.2% Ϯ 1.9% of all genes are dedicated to secondary metabolite synthesis, with some strains devoting ϳ5 to 6% of their genomes to such a purpose (Table S2A). These values remain below the biosynthetic ability of the most gifted actinomycetes but are comparable with those of other relevant bioactive molecule producers, such as bacteria belonging to the Bacillaceae, Oxalobacteraceae, and Pseudoalteromonadaceae families (Table S2B) (95)(96)(97).…”

Genome-based analysis for the bioactive potential of Streptomyces yeochonensis CN732, an acidophilic filamentous soil actinobacterium

“…Majority of the compounds of microbial origin discovered till date with antibiotic, antitumor, or immunosuppressive activities have been derived from Streptomyces [3]. Such bioactive compounds are produced by biosynthetic gene clusters (BGCs) that consist of genes arranged in close proximity within the bacterial genomes [4]. Based on their products, BGCs are in general classified as non-ribosomal peptide synthetases (NRPSs), polyketide synthases (PKSs), and those for saccharides, terpenoids, lanthipeptides and many others.…”