From glycine peptides uptake to toxin surge: Decoding adaptation mechanisms under organic nitrogen enrichment in Microcystis aeruginosa

The structural specificity of organic nitrogen sources in modulating cyanobacterial physiology and toxin production remains poorly understood. This study systematically evaluated the bioavailability of exogenous glycine peptides in Microcystis aeruginosa ( M. aeruginosa ) and their regulatory roles in algal growth and microcystins (MCs) synthesis through an integrated physiological and transcriptomic approach. Glycine peptides demonstrated hierarchical bioavailability: glycine (Gly) > Glycylglycine (Gly2) > Tetraglycylglycine (Gly4) > Hexaglycylglycine (Gly6) > Cycloglycylglycine (CGly2). Gly and Gly2 were rapidly assimilated by M. aeruginosa , supporting robust algal growth comparable to the control group with nitrate as nitrogen source, while CGly2 and Gly6 induced nitrogen stress, damaging biomass and photosynthetic pigments. Notably, M. aeruginosa cultured with Gly4 as sole nitrogen source uniquely enhanced intracellular MCs production, and shifted MCs variants toward the highly toxic MC-LR. The shift in MCs variants ratios (MC-RR/MC-LR) reflected nitrogen availability, demonstrating a trade-off between nitrogen storage and toxin potency. Transcriptomic profiling unveiled nitrogen-centric metabolic rewiring, resulting in enhanced nitrogen assimilation, mcy genes for MCs biosynthesis, photosynthetic efficiency, and resource reallocation. While exogenous glycine peptides represent only a minor component of organic nitrogen in natural systems, these findings provide mechanistic insights into how peptide structure can influence cyanobacterial physiology and toxin profiles, contributing to a more nuanced understanding of organic nitrogen utilization by harmful cyanobacteria.