天津古泻湖湿地微生物抗真菌活性成分的发掘

Fungal infections have become one of the important diseases that affect the quality of human life and health. With the extensive application of antifungal agents, the problems of fungal drug resistance have become increasingly prominent and the treatment of fungal infections has become increasingly difficult. Many marketed antifungal drugs were derived from microbial secondary metabolites, Therefore, from the microbiological resources to find compounds having antifungal activity is still an effective way for the development of antifungal agents. Wetlands provide microorganisms with a special living environment, which is more conducive to the specific fungi and the proliferation of actinomycetes for partial salinization soils, must contain rich microbial resources to find secondary metabolites with antifungal activity. The project will take Tianjin ancient lagoon wetlands rich microbial resources as the research object, and "microorganisms - fermentation culture - activity and chemical screening - extraction and separation - antifungal activity tracking - lead compounds" as research idea, to explore a number of important application value of microbial resources and antifungal activity of secondary metabolites and lay the foundation for research and development of innovative drugs with independent intellectual property rights.

真菌感染已成为影响人类生活质量、威胁生命健康的重要疾病之一。随着抗真菌药物的广泛应用，真菌的耐药问题日益凸显，使真菌感染的治疗变得越来越困难。因此研究新的高效安全的抗真菌药物成为国内外医疗领域的热点。目前上市的抗真菌药物中有很多来源于微生物次生代谢产物，所以从微生物资源中寻找具有抗真菌活性的化合物仍是开发抗真菌药物有效途径。湿地为微生物提供了一个特殊的生存环境，而且湿地土壤偏盐碱性，更有利于放线菌繁殖，同时也造就了真菌的特异性，因而必定蕴含了丰富多样的微生物资源，为寻找具有抗真菌活性的次生代谢产物提供了天然的宝库。本项目以天津古泻湖湿地丰富的微生物资源为研究对象，通过"湿地微生物-发酵培养-活性和化学筛选-提取分离-抗真菌活性追踪-先导化合物"的研究思路，发掘一批具有重要应用价值的微生物菌株资源及其抗真菌活性新次生代谢产物，为研发具有我国自主知识产权的创新药物奠定基础。

真菌的耐药问题日益凸显，寻找新的高效安全的抗真菌药物具有重要的意义。天津古泻湖湖湿地孕育了丰富的微生物资源，本项目从天津大黄堡、七里海古泻湖湿地采集的29泥样中，分离纯化出339株菌，其中包括放线菌248株，真菌91株。经过对菌株发酵产物进行活性和化学筛选筛选，选取了2株放线菌和1株真菌作为研究对象，进一步发掘菌株的次生代谢产物，寻找具有抗真菌活性的化合物。通过“湿地微生物-发酵培养-活性和化学筛选-提取分离-抗真菌活性追踪-先导化合物”的研究策略，目前已经分离纯化鉴定了化合物52个，其中包括3个新的Xanthones类化合物，抗真菌药物灰黄霉素。本项目首次以天津古泻湖湿地微生物为研究对象，不仅提供了丰富的菌株资源，还发现了新的化合物。