Bacterial Secondary Metabolite Biosynthetic Potential in Soil Varies with Phylum, Depth, and Vegetation Type

Abstract

Bacteria isolated from soils are major sources of specialized metabolites, including antibiotics and other compounds with clinical value that likely shape interactions among microbial community members and impact biogeochemical cycles. Yet, isolated lineages represent a small fraction of all soil bacterial diversity. It remains unclear how the production of specialized metabolites varies across the phylogenetic diversity of bacterial species in soils and whether the genetic potential for production of these metabolites differs with soil depth and vegetation type within a geographic region. We sampled soils and saprolite from three sites in a northern California Critical Zone Observatory with various vegetation and bedrock characteristics and reconstructed 1,334 metagenome-assembled genomes containing diverse biosynthetic gene clusters (BGCs) for secondary metabolite production. We obtained genomes for prolific producers of secondary metabolites, including novel groups within the Actinobacteria, Chloroflexi, and candidate phylum “Candidatus Dormibacteraeota.” Surprisingly, one genome of a candidate phyla radiation (CPR) bacterium coded for a ribosomally synthesized linear azole/azoline-containing peptide, a capacity we found in other publicly available CPR bacterial genomes. Overall, bacteria with higher biosynthetic potential were enriched in shallow soils and grassland soils, with patterns of abundance of BGC type varying by taxonomy. IMPORTANCE Microbes produce specialized compounds to compete or communicate with one another and their environment. Some of these compounds, such as antibiotics, are also useful in medicine and biotechnology. Historically, most antibiotics have come from soil bacteria which can be isolated and grown in the lab. Though the vast majority of soil bacteria cannot be isolated, we can extract their genetic information and search it for genes which produce these specialized compounds. These understudied soil bacteria offer a wealth of potential for the discovery of new and important microbial products. Here, we identified the ability to produce these specialized compounds in diverse and novel bacteria in a range of soil environments. This information will be useful to other researchers who wish to isolate certain products. Beyond their use to humans, understanding the distribution and function of microbial products is key to understanding microbial communities and their effects on biogeochemical cycles.

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

“…From the twelve BGCs detected in Gemmatimonadetes, eight bacteriocins were detected suggesting this phylum may contain a greater biosynthetic capacity than previously thought (Figure 3). Similarly, a recent metagenomics soil study described bacteriocins being the prominent gene cluster detected in the genomes of Gemmatimonadetes (Sharrar et al, 2020). We report the prevalence of bacteriocin clusters in the genome of Gemmatimonadetes recovered from hypersaline microbial mats which appear to share similar biosynthetic capacities seen in the genomes of Gemmatimonadetes inhabiting soil environments.…”

“…A previous 16S rRNA survey of Shark Bay microbial mats revealed the surface layer being dominated and overrepresented by Alpha-, Gammaproteobacteria, Bacteroidetes, and Cyanobacteria (Wong et al, 2015). A recent study also found BGCs from Gammaproteobacteria were enriched in shallow sections of soil (Sharrar et al, 2020). Gammaproteobacteria and Cyanobacteria are known prolific secondary metabolite producers and Bacteroidetes have previously been reported to encode for a range of bacteriocins thus supporting the relatively high count of BGCs at the surface layer (Wang et al, 2014;Lopetuso et al, 2019;Reddy et al, 2020).…”

Unexpected diversity of CPR bacteria and nanoarchaea in the rare biosphere of rhizosphere-associated grassland soil

“…Notable was the unexpected phylum-level diversity of CPR lineages in the concentrate metagenomes. Previously, a genome of TM7 (Saccharibacteria) was reported from the same soil, but sampled at less than 1x coverage from bulk soil (6), and Microgenomates and Parcubacteria have been genomically sampled twice at low abundance (12,16). To our knowledge, this is the first report of Pacearchaeota, Doudnabacteria and potentially a novel clade of Saccharibacteria in soil.…”

Mining for novel antibiotics in the age of antimicrobial resistance

“…Actinobacteria continue to be the main source of clinically used antimicrobials (van Bergeijk et al ., 2020), but genome mining strategies are revealing the enormous genetic potential of alternative microbial taxa to discover novel antibiotics (Blin et al ., 2019; Sharrar et al ., 2020). This fact is exemplified in a recent study in Microbial Biotechnology where the combination of genome mining and phylogenetics of core polyketide synthase domains led to the discovery of an uncharacterized 35 kb biosynthetic gene cluster (BGC) in a fungal endophyte isolated from a traditional Chinese medicine plant.…”

“…Despite AMR being a rising threat, recent efforts aimed at discovering and developing new antimicrobials in public and private sectors have not advanced significantly, with only 12 new antibiotics (or combinations) being approved in the last two decades (Kaufmann et al ., 2018). However, the rapid progress in the development of integrative platforms based on the combination of genomics, metagenomics, metabolomics and bioinformatics is facilitating the analysis of thousands of microorganisms in order to mine the antimicrobial biosynthetic potential of specific taxonomic groups and ecosystems (Sharrar et al ., 2020; van der Hooft et al ., 2020). In addition, recent algorithmic advancements in modelling neural networks have started to influence the paradigm of drug discovery (Stokes et al ., 2020).…”