2-Hydroxychalcone as a Novel Natural Photosynthesis Inhibitor against Bloom-Forming Cyanobacteria

The control of harmful cyanobacterial blooms has been becoming a global challenge. The development of eco-friendly algicides with strong specificity is urgently needed. The photosynthetic apparatus is a promising target site for algicides to minimize the possible harmful effects on animals and humans. In this study, biologically derived 2-hydroxychalcone efficiently inhibited the growth of bloom-forming M. aeruginosa by selectively interfering with photosynthesis. 2-Hydroxychalcone targeting Photosystem II (PSII) inhibited electron transfer between the primary and secondary electron acceptors (Q_A and Q_B) and the binding of plastoquinone (PQ) molecules to the Q_B binding pocket at the acceptor side of PSII, as revealed by polyphasic chlorophyll (Chl) a fluorescence induction and Q_A^- reoxidation kinetics. Molecular docking for 2-hydroxychalcone to D1 protein and the proteomic responses of M. aeruginosa suggested that 2-hydroxychalcone formed a stable monodentate ligand with the nonheme iron in D1 protein, provoking significant modulation of PSII proteins. The unique binding mode of 2-hydroxychalcone with PSII differentiated it from classical PSII inhibitors. Furthermore, 2-hydroxychalcone down-regulated the expression of microcystin (MC) synthesis-related genes to restrain MC synthesis and release. These results indicated the potential application of 2-hydroxychalcone as an algicide or a template scaffold for designing novel derivatives with superior algicidal activity.