Microbial community drivers of PK/NRP gene diversity in selected global soils

The 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.

Through 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.

The 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.