Abstract
Bacterial natural products (NPs) are still a major source of new drug leads. Polyketides (PKs) and non-ribosomal peptides (NRP) are two pharmaceutically important families of NPs and recent studies have revealed Antarctica to harbor endemic polyketide synthase (PKS) and non-ribosomal peptide synthetase (NRPS) genes, likely to be involved in the production of novel metabolites. Despite this, the diversity of secondary metabolites genes in Antarctica is still poorly explored. In this study, a computational bioprospection approach was employed to study the diversity and identity of PKS and NRPS genes to one of the most biodiverse areas in maritime Antarctica—Maxwell Bay. Amplicon sequencing of soil samples targeting ketosynthase (KS) and adenylation (AD) domains of PKS and NRPS genes, respectively, revealed abundant and unexplored chemical diversity in this peninsula. About 20% of AD domain sequences were only distantly related to characterized biosynthetic genes. Several PKS and NRPS genes were found to be closely associated to recently described metabolites including those from uncultured and candidate phyla. The combination of new approaches in computational biology and new culture-dependent and -independent strategies is thus critical for the recovery of the potential novel chemistry encoded in Antarctica microorganisms.
Highlights
Microorganisms, and bacteria in particular, produce a plethora of bioactive natural products (NPs), including clinically-relevant antibiotics, antifungals and anticancer agents, and continue to be a major source of new structural leads [1]
PKs and NRPs are biosynthesized by polyketide synthase (PKS) and non-ribosomal peptide synthetase (NRPS) enzymatic machinery, respectively [3]
1710 and 1012 OTUs were successfully retrieved for KS and AD domain of PKS and NRPS genes, respectively
Summary
Microorganisms, and bacteria in particular, produce a plethora of bioactive natural products (NPs), including clinically-relevant antibiotics, antifungals and anticancer agents, and continue to be a major source of new structural leads [1]. Conserved motifs on the genes encoding these enzymes have allowed for the design of degenerate primers [4,5], that have proved useful to determine PKS and NRPS phylogenetic diversity in natural ecosystems [6], and to predict (to some extent) their encoded chemical outputs [7]. Such primers target the highly conserved ketosynthase (KS) and adenylation (AD) domains of PKS and NRPS genes, respectively. A growing number of studies have employed the PCR-based sequence tag approach to uncover PKS and NRPS gene diversity across different environmental microbiomes [7,8,9]
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