Recovering Genomics Clusters of Secondary Metabolites from Lakes Using Genome-Resolved Metagenomics

Abstract

Metagenomic approaches became increasingly popular in the past decades due to decreasing costs of DNA sequencing and bioinformatics development. So far, however, the recovery of long genes coding for secondary metabolites still represents a big challenge. Often, the quality of metagenome assemblies is poor, especially in environments with a high microbial diversity where sequence coverage is low and complexity of natural communities high. Recently, new and improved algorithms for binning environmental reads and contigs have been developed to overcome such limitations. Some of these algorithms use a similarity detection approach to classify the obtained reads into taxonomical units and to assemble draft genomes. This approach, however, is quite limited since it can classify exclusively sequences similar to those available (and well classified) in the databases. In this work, we used draft genomes from Lake Stechlin, north-eastern Germany, recovered by MetaBat, an efficient binning tool that integrates empirical probabilistic distances of genome abundance, and tetranucleotide frequency for accurate metagenome binning. These genomes were screened for secondary metabolism genes, such as polyketide synthases (PKS) and non-ribosomal peptide synthases (NRPS), using the Anti-SMASH and NAPDOS workflows. With this approach we were able to identify 243 secondary metabolite clusters from 121 genomes recovered from our lake samples. A total of 18 NRPS, 19 PKS, and 3 hybrid PKS/NRPS clusters were found. In addition, it was possible to predict the partial structure of several secondary metabolite clusters allowing for taxonomical classifications and phylogenetic inferences. Our approach revealed a high potential to recover and study secondary metabolites genes from any aquatic ecosystem.

Discovery of an Abundance of Biosynthetic Gene Clusters in Shark Bay Microbial Mats

“…Natural product discovery efforts have mainly focused on marine and soil environments due to their rich biodiversity and biosynthetic potential. The BGC abundance observed in our dataset were found to be as high as those found in soil ecosystems and more enriched compared to a metagenomics lake study (Crits-Christoph et al, 2018;Cuadrat et al, 2018). We report the distribution of BGCs in Shark Bay microbial mats comparable with BGCs recovered from soil and water ecosystems thus supporting Shark Bay microbial mats as a possible new source of untapped biosynthetic potential.…”

Diversity of Bacterial Biosynthetic Genes in Maritime Antarctica

“…A large percentage (from 19% to 59% of relative abundance by sample) of the assembled KS OTUs were most closely related to environmental sample sequences, likely obtained from metagenome surveys as well as biosynthetic gene mining studies across the globe [13,59,60]. Regarding Actinobacteria, the chemically rich order Strepromycetales is widely distributed and accounts for 58% of KS domains sequences in sample 54 ( Figure 6C).…”

New Approaches to Detect Biosynthetic Gene Clusters in the Environment

“…Aquatic ecosystems are relatively unexplored but have been reported to harbor a high diversity of microorganisms, which may reflect the biosynthetic potential of these ecosystems [14,44]. A previous study observed marine Actinomycetes as a robust source for beneficial SMs [45].…”

“…In a recent study, antiSMASH and NAPDOS were used to screen for SMs in recovered genome bins from Lake Stechlin, north-east Germany [14]. Of the 243 BGCs identified, 125 were classified as terpenes and represent the most abundant cluster type.…”

“…To date, studies have screened for SMs in environments hosting large bacterial diversity and presumably large chemical diversity, such as aquatic ecosystems, soils and host microbiomes [13,14,15]. The purpose of this review is to highlight various methods used to identify BGCs in the environment and provide examples of how recent studies have explored the genetic basis for novel natural product synthesis, which have wide ranging medical and industrial applications.…”