海洋Uncultured放线菌资源挖掘及新天然产物发现

Marine actinomycetes are important sources of drug lead compounds. Uncultured actinomycetes, which constitute 99% of environmental actinomycetes, have yet been studied. Therefore, they are huge potential sources of microorganisms. Scientific evidences have demonstrated that in situ cultivation is the key to the growth of uncultured microbes. The present project plans to employ the new technique "Microbial Trap" which let actinomycetes grow in situ. Uncultured actinomycetes from surface sediments from the Dongji Island sea area (both near and far sea) are cultured in our lab, which are then purified by traditional methods and identified by molecular means to obtain pure cultures. Marine uncultured actinomycetes library with biological diversity will be established. Target strains are selected by gene and chemical screening. OSMAC strategy is applied to induce chemical diversity of secondary metabolics. Modern techniques for natural product isolation and characterization are used to discover marine bioactive natural products with novel chemical structures. This project will provide a new approach toward mining the rich source of marine actinomycetes in our country, and offer candidates for marine drug discovery.

海洋放线菌是药物先导化合物的重要来源。占海洋放线菌资源99％的Uncultured类群绝大多数未被研究，是潜在的巨大微生物资源。研究海洋Uncultured放线菌对海洋药物研发具有重要性和紧迫性。科学研究发现，"原位培养"是获得Uncultured微生物的关键。本项目拟采用放线菌原位培养新技术"Microbial Trap"，对东极岛海域（近海和远海）表层沉积物中的Uncultured放线菌进行实验室培养，结合经典放线菌分离纯化方法与分子鉴定技术，获得若干纯培养，建立多样性丰富的海洋Uncultured放线菌库。通过基因与化学筛选，确定目标菌株。应用OSMAC策略诱导次生代谢产物多样性，整合运用现代天然产物分离分析技术，发现若干具有新颖化学结构的海洋活性天然产物。本项目将为开发利用我国丰富的海洋放线菌资源探索新途径，为海洋药物开发提供新的研究对象。

海洋放线菌是药物先导化合物的重要来源。占海洋放线菌资源99％的Uncultured 类群绝大多数未被研究，是潜在的巨大微生物资源。本课题组采用放线菌原位培养新技术“Microbial Trap”，对东极岛海域（近海和远海）表层沉积物中的Uncultured 放线菌进行实验室培养，结合经典放线菌分离纯化方法与分子鉴定技术，建立多样性丰富的海洋Uncultured 放线菌库，共分离鉴定了68株放线菌，并筛选获得有研究潜力的海洋放线菌4株，其中一株为新种。整合运用现代天然产物分离分析技术，从中发现12个具有新颖化学结构的海洋活性天然产物。建立了海洋天然产物Streptochlorin的优化发酵方法。本项目为开发利用我国丰富的海洋放线菌资源探索了一种新途径，为海洋药物开发提供新的研究对象。