免疫抑制剂广泛应用于器官移植抗排斥反应和自身免疫性疾病的治疗，现有的免疫抑制剂多存在治疗范围小、价格昂贵、毒副作用多等缺点，快速增长的药物市场也迫切需要更多高效、低毒的新型免疫抑制剂的出现。本项目立足于丰富的昆虫共生菌资源，采用T淋巴细胞增殖实验模型，前期筛选获得了三株显示较强免疫抑制活性的昆虫共生菌，但活性物质基础、结构与强度的关系、选择性及作用机制还不明确。计划采用现代分离纯化技术，结合LC-MS/MS快速排重和免疫抑制活性导向追踪手段，高效快速分离结构新颖、活性显著的次生代谢产物；运用多种现代波谱学技术进行结构解析，并对单体化合物进行免疫抑制活性的综合评价；对活性强、毒性小、作用方式独特的单体化合物进行作用机理的初步研究，为研制新型免疫抑制药物提供先导化合物及相关理论和实验依据。该研究有望揭示昆虫共生菌卓越的生物合成潜力，为其成为寻找新活性天然产物的重要资源提供有力的证据。

Immunosuppressants have been widely used for anti-rejection response in organ transplantation and the treatment of autoimmune diseases. The existing immunosuppressants exhibit narrow therapeutic window, expensive cost, significant toxic effects, and other disadvantages. On the other hand, the demand of new immunosuppressive drugs with high efficacy and low toxicity is more and more urgent because of the rapidly increasing market. In order to search for immunosuppressive lead compounds, we have obtained three insect symbiotic microbes for further studies. These microbes, showing higher immunosuppressive bioactivity, were screened by the model of T lymphocytes transformation experiment. However, we do not clearly know the definite bioactive substances, structure-activity relationship, selectivity and mechanism. Firstly, we plan to isolate the new active secondary metabolites with the follow-up fractionation procedure co-guided by LC-MS/MS rapid dereplication and immunosuppressive activity bioassay. Secondly, The structures of the active compounds will be elucidated by many kinds of modern means of natural products research and spectroscopic methods. And the bioactivity will be comprehensive evaluatied by other screening models. Finally, we will select the monomer with stronger bioactivity, less toxicity and distinct mode of action to study the mechanism. This research will give some lead compounds, related theories, and experimental bases for the development of new immunosuppressive drugs. The study aims to reveal the excellence in the biosynthetic potential of the insect symbiotic microbes. It will provide powerful evidence that the insect symbiotic microbes might become important resources for new active natural products.