Expression of Microcystis biosynthetic gene clusters in natural populations suggests temporally dynamic synthesis of novel and known secondary metabolites in western Lake Erie

SummaryMicrocystis spp. produces diverse secondary metabolites within freshwater cyanoHABs around the world. In addition to the biosynthetic gene clusters (BGCs) encoding known compounds, Microcystis genomes harbor numerous BGCs of unknown function, indicating its poorly understood chemical repertoire. While recent studies show that Microcystis produces several metabolites in the lab and field, little work has focused on analyzing the abundance and expression of its broader suite of BGCs during cyanoHAB events. Here, we use metagenomic and metatranscriptomic approaches to track the relative abundance of Microcystis BGCs and their transcripts throughout the 2014 western Lake Erie cyanoHAB. Results indicate the presence of several transcriptionally active BGCs that are predicted to synthesize both known and novel secondary metabolites. The abundance and expression of these BGCs shifted throughout the bloom, with transcript abundance levels correlating with temperature, nitrate and phosphorus concentrations, and the abundance of co-occurring predatory and competitive eukaryotic microorganisms, suggesting the importance of both abiotic and biotic controls in regulating expression. This work highlights the need for understanding the chemical ecology and potential risks to human and environmental health posed by secondary metabolites that are produced but unmonitored, as well as the potential discovery of pharmaceutical compounds from cyanoHAB-derived BGCs. Originality-Statement of SignificanceMicrocystis spp. dominate cyanobacterial harmful algal blooms (cyanoHABs) worldwide and pose significant threats to water quality through the production of numerous secondary metabolites, many of which are toxic. While the toxicity and biochemistry of microcystins and several other compounds have been well studied, the broader suite of secondary metabolites produced by Microcystis remains poorly understood, leaving gaps in our understanding of their impacts on ecology, human and ecosystem health, or potential pharmaceutical application. In this study, we use metagenomic and transcriptomic datasets to examine the diversity of genes encoding synthesis of secondary metabolites in natural Microcystis populations and assess their patterns of transcription in the context of biotic and abiotic conditions in western Lake Erie cyanoHABs. Our results reveal the presence of a large diversity of both known gene clusters that encode toxic secondary metabolites as well as novel ones that encode cryptic compounds. This research highlights the need for targeted studies of the secondary metabolite diversity in western Lake Erie, a vital freshwater source to the United States and Canada.