Secondary metabolism of <i>Microcystis</i> : current understanding and recent advances in unlocking genomic and chemical diversity

The cyanobacterial genus <i>Microcystis</i> is globally distributed and known for its ability to produce microcystins, a structurally diverse group of cyanotoxins. However, the biosynthetic capacity of <i>Microcystis</i> is vast; its diverse genomes contain a variety of biosynthetic gene clusters (BGCs) encoding the synthesis of metabolites that may be toxic, have important ecological function, or have applications for biotechnology or drug discovery. Recent studies illustrate that these BGCs vary significantly across <i>Microcystis</i> strains, can be highly expressed in environmental conditions, and may play key roles in cellular physiology, grazer deterrence, and microbial interactions. However, many of these BGCs and metabolites remain poorly characterized or completely uncharacterized, having been identified only through genome sequencing or mass spectrometry, respectively, leaving no knowledge of their structure, bioactivity, or physiological or ecological functions. Here, we synthesize the current body of knowledge regarding the secondary metabolism of <i>Microcystis</i> in terms of genetic and chemical diversity, potential drivers of synthesis, and physiological and ecological functions. This review highlights the need for further research to characterize the largely unexplored genetic and chemical diversity of <i>Microcystis</i> in communities in the environment and discusses the challenges and opportunities of integrating high-throughput multiomic approaches to link uncharacterized gene clusters with their corresponding metabolites. <i>Microcystis</i> will continue to be a rich source for secondary metabolite research as its genetic and chemical potential likely plays a critical role in the persistence and observed dynamics of harmful algal blooms and may harbor uncharacterized toxins and metabolites.