Multi-omics profiling of Earth’s biomes reveals that microbial and metabolite composition are shaped by the environment

Abstract Microbes produce an array of secondary metabolites that perform diverse functions from communication to defense1. These metabolites have been used to benefit human health and sustainability2. In their analysis of the Genomes from Earth’s Microbiomes (GEM) catalog3, Nayfach and co-authors observed that, whereas genes coding for certain classes of secondary metabolites are limited or enriched in certain microbial taxa, “specific chemistry is not limited or amplified by the environment, and that most classes of secondary metabolites can be found nearly anywhere”. Although metagenome mining is a powerful way to annotate biosynthetic gene clusters (BCGs), chemical evidence is required to confirm the presence of metabolites and comprehensively address this fundamental hypothesis, as metagenomic data only identify metabolic potential. To describe the Earth’s metabolome, we use an integrated omics approach: the direct survey of metabolites associated with microbial communities spanning diverse environments using untargeted metabolomics coupled with metagenome analysis. We show, in contrast to Nayfach and co-authors, that the presence of certain classes of secondary metabolites can be limited or amplified by the environment. Importantly, our data indicate that considering the relative abundances of secondary metabolites (i.e., rather than only presence/absence) strengthens differences in metabolite profiles across environments, and that their richness and composition in any given sample do not directly reflect those of co-occurring microbial communities, but rather vary with the environment.