蓝藻II型FBAase抑制剂的生物合理设计与筛选研究

The class II fructose-1,6-bisphosphate aldolases (FBAase-II) are essential enzymes used in calvin cycle and glycolysis. Because of their occurrence in lower organisms such as bacteria, fungus and microalgae, and their absence in humans and animals, the FBAase-II could be such promising new potential "green" targets. Recent studies on molecular biology and transgenosis suggest that, FBAase-II are also can be treated as the novel targets for designing algaecides, however, no inhibitors of FBAase-II from algae were reported hitherto. Thus, integrating use of molecular simulation, gene, enzyme engineering and spectral analysis, the interactional mechanism between cyanobacteria FBAase-II and their substrate or probe molecule (lead inhibitors) were investigated. On the basis of the structure and interactional mechanism, we plan to rationally design, screen, optimize, synthesis and get novel high efficient inhibitors targeted into the cyanobacteria FBAase-II. The research is expected to provide us new ideas and some preliminary research for development of novel algaecides.

II型果糖-1,6-二磷酸醛缩酶(FBAase-II)是Calvin循环和糖质新生代谢过程中必不可少的一个调控酶。由于其只存在于藻类、细菌和真菌等低等生物中，在人和动物体内不存在，FBAase-II被作为一个最具潜力的"绿色"新靶标而越来越引起人们的关注。最近的分子生物学和转基因研究也表明，FBAase-II可被选作杀藻剂作用的潜在新靶标而进行研究，但以藻类FBAase-II为靶标的抑制剂却鲜有报道。因此，本项目拟综合运用分子模拟、基因克隆表达、定点突变、光谱表征等技术，系统深入地研究蓝藻FBAase-II与配体相互作用的分子机制，以获得准确可靠的酶-配体相互作用模型，并在此基础上合理设计、筛选及合成蓝藻FBAase-II抑制剂先导结构，为高效、绿色、具有应用前景的新型农药杀藻剂的研究工作提供一定的创制思路和前期研究基础

II型果糖-1,6-二磷酸醛缩酶(FBA-II)是Calvin循环和糖质新生代谢过程中必不可少的一个调控酶。由于其只存在于藻类、细菌和真菌等低等生物中，在人和动物体内不存在，FBAase-II被作为一个最具潜力的“绿色”新靶标而越来越引起人们的关注。最近的分子生物学和转基因研究也表明，FBA-II可被选作杀藻剂作用的潜在新靶标而进行研究，但以藻类FBA-II为靶标的抑制剂却鲜有报道。因此，本项目拟综合运用分子模拟、基因克隆表达、定点突变、光谱表征等技术，系统深入地研究蓝藻FBA-II (Cy-FBA-II) 与配体相互作用的分子机制，以获得准确可靠的酶-配体相互作用模型，并在此基础上合理设计、筛选及合成Cy-FBA-II抑制剂先导结构，为高效、绿色、具有应用前景的新型农药杀藻剂的研究工作提供一定的创制思路和前期研究基础