Abstract
BackgroundThe emergence of antibiotic-resistant pathogens has created an urgent need for novel antimicrobial treatments. Advances in next-generation sequencing have opened new frontiers for discovery programmes for natural products allowing the exploitation of a larger fraction of the microbial community. Polyketide (PK) and non-ribosomal pepetide (NRP) natural products have been reported to be related to compounds with antimicrobial and anticancer activities. We report here a new culture-independent approach to explore bacterial biosynthetic diversity and determine bacterial phyla in the microbial community associated with PK and NRP diversity in selected soils.ResultsThrough amplicon sequencing, we explored the microbial diversity (16S rRNA gene) of 13 soils from Antarctica, Africa, Europe and a Caribbean island and correlated this with the amplicon diversity of the adenylation (A) and ketosynthase (KS) domains within functional genes coding for non-ribosomal peptide synthetases (NRPSs) and polyketide synthases (PKSs), which are involved in the production of NRP and PK, respectively. Mantel and Procrustes correlation analyses with microbial taxonomic data identified not only the well-studied phyla Actinobacteria and Proteobacteria, but also, interestingly, the less biotechnologically exploited phyla Verrucomicrobia and Bacteroidetes, as potential sources harbouring diverse A and KS domains. Some soils, notably that from Antarctica, provided evidence of endemic diversity, whilst others, such as those from Europe, clustered together. In particular, the majority of the domain reads from Antarctica remained unmatched to known sequences suggesting they could encode enzymes for potentially novel PK and NRP.ConclusionsThe approach presented here highlights potential sources of metabolic novelty in the environment which will be a useful precursor to metagenomic biosynthetic gene cluster mining for PKs and NRPs which could provide leads for new antimicrobial metabolites.
Highlights
The emergence of antibiotic-resistant pathogens has created an urgent need for novel antimicrobial treatments
We have developed a target assay based on the adenylation (A) domain of the non-ribosomal peptide synthetases (NRPSs) and the ketosynthase (KS) domain of polyketide synthases (PKSs) resulting in amplification of non-conserved regions of these genes that can be used for defining novel metabolic capability [27]
The geographic segregation of different microbial communities revealed in this study highlights the potential for novel PK and non-ribosomal pepetide (NRP) discovery in soils exposed to extreme conditions, such as those of Antarctica, the Algerian Saharan Desert or the pristine Cuban Cayo-Blanco regions
Summary
The emergence of antibiotic-resistant pathogens has created an urgent need for novel antimicrobial treatments. Polyketide (PK) and non-ribosomal pepetide (NRP) natural products have been reported to be related to compounds with antimicrobial and anticancer activities. The current dearth of antimicrobial compounds with novel modes of action means that we Genome sequencing has revolutionised natural product discovery with the identification of biosynthetic gene clusters (BGCs) encoding for the production of natural (2019) 7:78 products accounting > 10% of some bacterial genomes such as in the case of Actinomycetes [5, 7]. Evidence suggests natural products likely have a role in signalling and protection, with recent studies showing antibiotics playing a key role in antagonism within ant communities and as protective agents in wasps’ nests [11]. Recent genomic evidence has demonstrated that the less well-characterised Bacteroidetes, Verrucomicrobia and Planctomycetes harbour novel BGCs [12,13,14], though the functions of these are widely unknown
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