Pseudomonas fluorescens is a prevalent spoilage bacterium in various chilled aquatic products, producing toxic biogenic amines (BAs) through the decarboxylation of amino acids via amino acid decarboxylases. Our previous studies revealed that P. fluorescens PF12 regulates BA production through its quorum sensing (QS) system, suggesting that disrupting QS could be a potential approach to control BA generation. In this study, we targeted the three-dimensional structure of the LuxI-type protein in P. fluorescens PF12 to screen for QS inhibitors (QSIs) through high-throughput screening from Seaweed Metabolite Database and Comprehensive Marine Natural Products Database. Nine compounds with high binding scores to the LuxI-type protein were identified. Considering cost-effectiveness and safety, phytol was selected for further investigation. Experimental results demonstrated that sub-inhibitory concentrations of phytol significantly suppressed BA production, siderophore production, motility, extracellular protease secretion, and biofilm formation in P. fluorescens PF12. Specifically, when the salmon fillets were stored for 288 h, the histamine content in the fillets treated with 25 mg/mL phytol decreased by 43.81 %. RT-qPCR revealed that the expression levels of key genes hisD and hisC related to histamine synthesis in the phytol treatment group were reduced by 7.68 ( p < 0.05) and 8.23 % ( p < 0.05), respectively, compared to the control group. Molecular docking analysis revealed that phytol interacts with key residues in the LuxI-type protein, thereby blocking the synthesis of acyl-homoserine lactones (AHLs) and downstream QS signaling. These findings indicate that phytol has great potential for controlling BA production in aquatic products and ensuring food safety.
Targeting ferroptosis, an iron-dependent form of regulated cell death triggered by the lethal overload of lipid peroxides, in cancer therapy is impeded by our limited understanding of the intersection of tumour’s metabolic feature and ferroptosis vulnerability. In the present study, arginine is identified as a ferroptotic promoter using a metabolites library. This effect is mainly achieved through arginine’s conversion to polyamines, which exerts their potent ferroptosis-promoting property in an H 2 O 2 -dependent manner. Notably, the expression of ornithine decarboxylase 1 (ODC1), the critical enzyme catalysing polyamine synthesis, is significantly activated by the ferroptosis signal——iron overload——through WNT/MYC signalling, as well as the subsequent elevated polyamine synthesis, thus forming a ferroptosis-iron overload-WNT/MYC-ODC1-polyamine-H 2 O 2 positive feedback loop that amplifies ferroptosis. Meanwhile, we notice that ferroptotic cells release enhanced polyamine-containing extracellular vesicles into the microenvironment, thereby further sensitizing neighbouring cells to ferroptosis and accelerating the “spread” of ferroptosis in the tumour region. Besides, polyamine supplementation also sensitizes cancer cells or xenograft tumours to radiotherapy or chemotherapy through inducing ferroptosis. Considering that cancer cells are often characterized by elevated intracellular polyamine pools, our results indicate that polyamine metabolism exposes a targetable vulnerability to ferroptosis and represents an exciting opportunity for therapeutic strategies for cancer.
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