Uncharted biosynthetic potential of the ocean microbiome

Abstract

Microbes are phylogenetically and metabolically diverse. Yet capturing this diversity, assigning functions to host organisms and exploring the biosynthetic potential in natural environments remains challenging. We reconstructed >25,000 draft genomes, including from >2,500 uncharacterized species, from globally-distributed ocean microbial communities, and combined them with ~10,000 genomes from cultivated and single cells. Mining this resource revealed ~40,000 putative biosynthetic gene clusters (BGCs), many from unknown phylogenetic groups. Among these, we discovered Candidatus Eudoremicrobiaceae as one of the most biosynthetically diverse microbes detected to date. Discrete transcriptional states structuring natural populations were associated with a potentially niche-partitioning role for BGC products. Together with the characterization of the first Eudoremicrobiaceae natural product, this study demonstrates how microbiomics enables prospecting for candidate bioactive compounds in underexplored microbes and environments.

The rumen microbiome inhibits methane formation through dietary choline supplementation

“…All raw sequences can be accessed through the NCBI at BioProject PRJEB43305, and the code for all the analyses were detailed in submitted publication by Paoli et al . 60 .…”

A roadmap for metagenomic enzyme discovery

“…To enable marine bioprospecting, several studies have published meta-omics data resources [239][240][241][242] including the Tara Oceans sampling expeditions which sequenced over 600 metatranscriptomes and 1000 metagenomes from >200 globallydistributed sampling stations. 23 The combination of Tara Oceans data with Global Ocean Sampling, 10 Malaspina, 241 and bioGEOTRACES expeditions 240 enabled the assembly of the largest genome-resolved ocean resource to date.…”

“…Previous analysis in our lab also found that reference genomes from cultivated marine isolates rarely overlapped with marine SAGs or MAGs, indicating that multipronged approaches of cultivation and multiple types of sequencing contributes to a greater genome-resolved understanding of ecological community composition. 242 There are still relatively few cases of biosynthetic enzyme discovery from SAGs. As the earliest example applied to natural product studies, Grindberg et al detected the cyanobacterial apratoxin biosynthetic pathway in a mixed bacterial assemblage through a combination of single-cell sequencing, in silico mining, and a metagenomic fosmid library screening.…”

“… 239 From these data, >25 000 metagenome-assembled genomes were constructed and, together with ∼10 000 marine single and isolate genomes, processed with antiSMASH, 94 leading to the identification and functional characterization of new BGCs and biosynthetic enzymes. 242 The scale of this metagenomics repository for one specific environment type is perhaps only paralleled by the Human Microbiome Project. 24 Compared to the human gut microbiome, however, the variable ocean conditions promote a greater diversity of enzymes, particularly along the water column where a gradient of different temperature and pressure conditions exist.…”

“…Previous analysis in our lab also found that reference genomes from cultivated marine isolates rarely overlapped with marine SAGs or MAGs, indicating that multi-pronged approaches of cultivation and multiple types of sequencing contributes to a greater genome-resolved understanding of ecological community composition. 242 …”