Abstract Toxic cyanobacterial harmful algal blooms (cyanoHABs) threaten freshwater resources globally and are intensifying with increasing eutrophication. Bloom toxicity is strongly influenced by intraspecific variation in the biosynthetic repertoires of toxic cyanobacteria, yet few studies examine the diversity of cyanobacterial cyanopeptides beyond hepatotoxic microcystins. To understand the dynamics and drivers of cyanopeptide diversity in cyanoHABs, we analyzed temporal patterns of cyanobacteria, metabolites, and their biosynthetic gene clusters (BGCs) in western Lake Erie using a seven-year time series (2016–2022) of metagenomic and metabolomic data. Our findings demonstrate that shifts from Microcystis to Dolichospermum occur later in the bloom season, coinciding with lower temperatures. Modules of co-varying BGCs (biosynthesis modules) from these genera were identified with hierarchical clustering, with uncharacterized BGCs among the most abundant. Biosynthesis modules rich in nonribosomal peptide synthetases (NRPS) peaked in early August, coinciding with elevated levels of inorganic nitrogen, warmer temperatures, and high Microcystis abundance. In contrast, modules rich in polyketide synthases (PKS) and ribosomally synthesized and post-translationally modified peptides (RiPPs) peaked following the Microcystis maximum in mid-August. Metabolomic analyses confirmed that metabolites followed shared seasonal patterns with their associated biosynthesis modules, forming three phases characterized by (1) microcystins, (2) anabaenopeptins and aeruginosins, and (3) aerucyclamides. These phases co-varied with bottom-up and top-down pressures, with later phases coinciding with increased microbially processed organic nitrogen and reduced detection of grazers. This study demonstrates consistent seasonal patterns of cyanobacterial metabolite succession and co-occurrence beyond microcystins, suggesting tradeoffs between biosynthetic resource demands and ecological controls.
Hart et al. (2026) studied this question.