The potential of the diverse chemistries present in natural products (NP) for biotechnology and medicine remains untapped because NP databases are not searchable with raw data and the NP community has no way to share data other than in published papers. Although mass spectrometry techniques are well-suited to high-throughput characterization of natural products, there is a pressing need for an infrastructure to enable sharing and curation of data. We present Global Natural Products Social molecular networking (GNPS, http://gnps.ucsd.edu), an open-access knowledge base for community wide organization and sharing of raw, processed or identified tandem mass (MS/MS) spectrometry data. In GNPS crowdsourced curation of freely available community-wide reference MS libraries will underpin improved annotations. Data-driven social-networking should facilitate identification of spectra and foster collaborations. We also introduce the concept of ‘living data’ through continuous reanalysis of deposited data.

Microbial communities often undergo intricate compositional changes yet also maintain stable coexistence of diverse species. The mechanisms underlying long-term coexistence remain unclear as system-wide studies have been largely limited to engineered communities, ex situ adapted cultures, or synthetic assemblies. Here we show how kefir, a natural milk-fermenting community of prokaryotes (predominantly lactic and acetic acid bacteria) and yeasts (family Saccharomycetaceae), realizes stable coexistence through spatiotemporal orchestration of species and metabolite dynamics. During milk fermentation, kefir grains (a polysaccharide matrix synthesized by kefir microbes) grow in mass but remain unchanged in composition. In contrast, the milk is colonized in a sequential manner in which early members open the niche for the followers by making available metabolites like amino acids and lactate. Through metabolomics, transcriptomics and large-scale mapping of inter-species interactions, we show how microbes poorly suited for milk survive in — and even dominate — the community, through metabolic cooperation and uneven partitioning between grain and milk. Overall, our findings reveal how inter-species interactions partitioned in space and time lead to stable coexistence.

We here combine chemical analysis and genomics to probe for new bioactive secondary metabolites based on their pattern of distribution within bacterial species. We demonstrate the usefulness of this combined approach in a group of marine Gram-negative bacteria closely related to Pseudoalteromonas luteoviolacea, which is a species known to produce a broad spectrum of chemicals. The approach allowed us to identify new antibiotics and their associated biosynthetic pathways. Combining chemical analysis and genetics is an efficient “mining” workflow for identifying diverse pharmaceutical candidates in a broad range of microorganisms and therefore of great use in bioprospecting.

Microbial communities in nature often feature complex compositional dynamics yet also stable coexistence of diverse species. The mechanistic underpinnings of such dynamic stability remain unclear as system-wide studies have been limited to small engineered communities or synthetic assemblies. Here we show how kefir, a natural milk-fermenting community, realizes stable coexistence through spatio-temporal orchestration of species and metabolite dynamics. During milk fermentation, kefir grains (a polysaccharide matrix synthesized by kefir microbes) grow in mass but remain unchanged in composition. In contrast, the milk is colonized in a dynamic fashion with early members opening metabolic niches for the followers. Through large-scale mapping of metabolic preferences and inter-species interactions, we show how microbes poorly suited for milk survive in, and even dominate the community through metabolic cooperation and uneven partitioning between the grain and the liquid phase. Overall, our findings reveal how spatio-temporal dynamics promote stable coexistence and have implications for deciphering and modulating complex microbial ecosystems.

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