微囊藻毒素及其转化产物抑制蛋白磷酸酶PP1/PP2A的毒性差异机制研究

Evaluation and regulation on the biological toxicity effect of Microcystins (MCs) and their derivants was an important guarantee of drinking water safety. Based on the characteristics of MCs pollution, the chemical structures of MCs, the toxic mechanism on PPs and related regulation strategies, MC derivants were obtained by simulating the chlorination process, the electrophilic addition reaction and the microbial degradation process target to MCs. Based on MCs/MC derivants identification and preparation, the toxicity of MCs and their derivatives on protein phosphatases was analyzed by means of molecular toxicity test. Then, the regulating mechanism for the toxicity of MCs and their derivatives was investigated in combination with enzyme activity experiment and molecular simulation technology. Based on the biological toxicity features of MCs and MC derivatives, the related regulation processes for MCs could be optimized or adjust to reduce the risk of MCs. This study not only contributes to a comprehensive cognition on the hazards and control strategy for MCs, but also offers valid technique support for the safety of drinking water supply.

微囊藻毒素(MCs)及其转化产物的生物毒性效应评价与调控是饮用水安全供给的重要保障，对全面认识和防控微囊藻毒素的环境风险具有重要意义。本研究拟通过分析MCs污染特性、毒性作用机制与各类调控策略，以MCs为基础研究物，通过模拟氯消毒工艺、巯醇亲电加成反应、微生物降解过程制取MCs的各类转化产物；在MCs及其转化产物的结构准确鉴定和相应产物制备的基础上，借助分子毒性试验和分子对接模拟技术对MCs及其转化产物的毒性作用进行解析；将理论模拟数据与毒性试验结果相对照，探究MCs及其转化产物抑制蛋白磷酸酶PP1/PP2A生物活性的毒性作用差异机制，建立了对MCs及其转化产物毒性效应进行全面评价的新方法。本研究有利于全面认识微囊藻毒素的毒性危害与调控策略，并能够为饮用水的安全供给提供科学的技术支持与保障。预计发表SCI论文5-8篇，其中IF≥3的3-4篇。

微囊藻毒素(MCs)及其转化产物的生物毒性效应评价与调控是饮用水安全供给的重要保障，对全面认识和防控微囊藻毒素的环境风险具有重要意义。本研究通过分析MCs污染特性、毒性作用机制与各类调控策略，以MCs为基础研究物，通过模拟氯消毒工艺、巯醇亲电加成反应、微生物降解过程制取MCs的各类转化产物；在MCs及其转化产物的结构准确鉴定和相应产物制备的基础上，借助分子毒性试验和分子对接模拟技术对MCs及其转化产物的毒性作用进行解析；将理论模拟数据与毒性试验结果相对照，探究MCs及其转化产物抑制蛋白磷酸酶PP1/PP2A生物活性的毒性作用差异机制，建立了对MCs及其转化产物毒性效应进行全面评价的新方法。本研究有利于全面认识微囊藻毒素的毒性危害与调控策略，并能够为饮用水的安全供给提供科学的技术支持与保障。本课题发表SCI论文15篇，其中IF≥3的15篇。