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ABSTRACT Coral reefs are experiencing unprecedented loss in coral cover due to increased incidence of disease and bleaching events. Thus, understanding mechanisms of disease susceptibility and resilience, which vary by species, is important. In this regard, untargeted metabolomics serves as an important hypothesis-building tool enabling the delineation of molecular factors underlying disease susceptibility or resilience. In this study, we characterize metabolomes of four species of visually healthy stony corals, includingMeandrina meandrites,Orbicella faveolata,Colpophyllia natans, andMontastraea cavernosa, collected at least a year before stony coral tissue loss disease reached the Dry Tortugas, Florida, and demonstrate that both symbiont and host-derived biochemical pathways vary by species. Metabolomes ofMeandrina meandritesdisplayed minimal intraspecies variability and the highest biological activity against coral pathogens when compared to other species in this study. The application of advanced metabolite annotation methods enabled the delineation of several pathways underlying interspecies variability. Specifically, endosymbiont-derived vitamin E family compounds, betaine lipids, and host-derived acylcarnitines were among the top predictors of interspecies variability. Since several metabolite features that contributed to inter- and intraspecies variation are synthesized by the endosymbiotic Symbiodiniaceae, which could be a major source of these compounds in corals, our data will guide further investigations into these Symbiodiniaceae-derived pathways. IMPORTANCEPrevious research profiling gene expression, proteins, and metabolites produced during thermal stress have reported the importance of endosymbiont-derived pathways in coral bleaching resistance. However, our understanding of interspecies variation in these pathways among healthy corals and their role in diseases is limited. We surveyed the metabolomes of four species of healthy corals with differing susceptibilities to the devastating stony coral tissue loss disease and applied advanced annotation approaches in untargeted metabolomics to determine the interspecies variation in host and endosymbiont-derived pathways. Using this approach, we propose the survey of immune markers such as vitamin E family compounds, acylcarnitines, and other metabolites to infer their role in resilience to coral diseases. As time-resolved multi-omics datasets are generated for disease-impacted corals, our approach and findings will be valuable in providing insight into the mechanisms of disease resistance. 

ABSTRACT Microcystisspp. are renowned for producing the hepatotoxin microcystin in freshwater cyanobacterial harmful algal blooms around the world, threatening drinking water supplies and public and environmental health. However,Microcystisgenomes also harbor numerous biosynthetic gene clusters (BGCs) encoding the biosynthesis of other secondary metabolites, including many with toxic properties. Most of these BGCs are uncharacterized and currently lack links to biosynthesis products. However, recent field studies show that many of these BGCs are abundant and transcriptionally active in natural communities, suggesting potentially important yet unknown roles in bloom ecology and water quality. Here, we analyzed 21 xenicMicrocystiscultures isolated from western Lake Erie to investigate the diversity of the biosynthetic potential of this genus. Through metabologenomic andin silicoapproaches, we show that theseMicrocystisstrains contain variable BGCs, previously observed in natural populations, and encode distinct metabolomes across cultures. Additionally, we find that the majority of metabolites and gene clusters are uncharacterized, highlighting our limited understanding of the chemical repertoire ofMicrocystisspp. Due to the complex metabolomes observed in culture, which contain a wealth of diverse congeners as well as unknown metabolites, these results underscore the need to deeply explore and identify secondary metabolites produced byMicrocystisbeyond microcystins to assess their impacts on human and environmental health.IMPORTANCEThe genusMicrocystisforms dense cyanobacterial harmful algal blooms (cyanoHABs) and can produce the toxin microcystin, which has been responsible for drinking water crises around the world. While microcystins are of great concern,Microcystisalso produces an abundance of other secondary metabolites that may be of interest due to their potential for toxicity, ecological importance, or pharmaceutical applications. In this study, we combine genomic and metabolomic approaches to study the genes responsible for the biosynthesis of secondary metabolites as well as the chemical diversity of produced metabolites inMicrocystisstrains from the Western Lake Erie Culture Collection. This unique collection comprisesMicrocystisstrains that were directly isolated from western Lake Erie, which experiences substantial cyanoHAB events annually and has had negative impacts on drinking water, tourism, and industry.