Recent Advances in Cyanotoxin Synthesis and Applications: A Comprehensive Review.

Over the past few decades, nearly 300 known cyanotoxins and more than 2000 cyanobacterial secondary metabolites have been reported from the environment. Traditional studies have focused on the toxic cyanotoxins produced by harmful cyanobacteria, which pose a risk to both human beings and wildlife, causing acute and chronic poisoning, resulting in diarrhea, nerve paralysis, and proliferation of cancer cells. Actually, the biotechnological potential of cyanotoxins is underestimated, as increasing studies have demonstrated their roles as valuable products, including allelopathic agents, insecticides and biomedicines. To promote a comprehensive understanding of cyanotoxins, a critical review is in demand. This review aims to discuss the classifications; biosynthetic pathways, especially heterogenous production; and potential applications of cyanotoxins. In detail, we first discuss the representative cyanotoxins and their toxic effects, followed by an exploration of three representative biosynthetic pathways (non-ribosomal peptide synthetases, polyketide synthetases, and their combinations). In particular, advances toward the heterologous biosynthesis of cyanotoxins in vitro and in vivo are summarized and compared. Finally, we indicate the potential applications and solutions to bottlenecks for cyanotoxins. We believe that this review will promote a comprehensive understanding, synthetic biology studies, and potential applications of cyanotoxins in the future.