Unraveling the inhibitory mechanism of composite allelochemicals on Microcystis aeruginosa: Integrated transcriptomic and metabolomic insights

Harmful cyanobacterial blooms (HCBs), driven by eutrophication, pose critical threats to aquatic ecosystems and public health. Current studies focused on inhibitory effect of single-component allelochemical on HCBs, yet cyanobacteria in natural environments are simultaneously exposed to multiple allelochemicals. Thus, it is more meaningful to study composite allelochemicals formulation for HCBs control. Our previous study found that the composite allelochemicals agent of 4-tert-butylcatechol and l -lysine (CAA-TL) can synergistically inhibit the growth of Microcystis aeruginosa . In this study, we investigated the inhibitory mechanism of CAA-TL against M. aeruginosa , integrating physiological, transcriptomic, and metabolomic approaches. CAA-TL reduced the cell density of M. aeruginosa by more than 90 % within four days, and significantly decreased the Chl- a content and chlorophyll fluorescence parameters. The integrated transcriptomic and metabolomic results showed that: (1) 471 upregulated and 312 downregulated differential expressed genes (DEGs) and 433 upregulated and 215 downregulated differential metabolites (DMs) were identified; (2) CAA-TL markedly impacted the expression of photosynthesis related genes (e.g., PsbA , PsbL , PsaB and PsaK ) indicating the inhibition of photosynthetic activity; (3) CAA-TL impacted DNA and protein synthesis through downregulation of nucleotide metabolism; (4) CAA-TL disrupted energy supply via the dysregulation of energy metabolism pathways. These findings reveal the inhibitory mechanism of CAA-TL via an integrated omics approach and provide theoretical support for their eco-friendly application in HCBs control.