基于iChip技术的海洋“未培养”微生物资源挖掘及新天然产物发现

海洋独特的生态环境孕育了海洋微生物复杂的生命机制，占海洋微生物资源99％以上的“未培养”类群因无法用传统技术培养而未被有效利用，是具有巨大潜在应用前景的新资源。科学证据表明，绝大多数微生物的生长依赖于特定生境以及微生物种群之间的群体感应与化学交流，因此，“原位培养”是获得“未培养”微生物的关键。本项目拟运用高通量原位培养新技术iChip，以红树林沉积物、近海沉积物、海水等作为研究对象，原位培养获得多样性丰富的海洋“未培养”微生物新资源，通过多相分类法鉴定若干新分类单元。运用分子网络技术研究其次级代谢产物的化学多样性与独特性，结合现代色谱和波谱方法，发现具有新颖化学结构的天然产物。并进一步开展体外抗菌、抗肿瘤、抗阿尔兹海默病活性筛选，获得高活性化合物。本项目的实施将为挖掘利用海洋“未培养”微生物新资源开辟一条有效途径，为我国海洋创新药物研发提供新的对象。

The marine special ecological environment has led to complex life mechanism of marine microbes. However, more than 99% of marine microbial resource still can’t be cultured by traditional cultivation technique. Marine uncultured microbes are therefore new resource with huge application potential. Scientific evidence showed that most microbes need special environment and chemical communication among them to grow. Therefore, in situ cultivation is the key to access uncultured microbes. This project plans to use new high-throughput in situ cultivation technique iChip to cultivate marine uncultured microbes with rich biodiversity from mangrove sediment, nearshore sediment, and sea water. Polyphasic approach is employed to characterize new taxa. Their secondary metabolites are analyzed by molecular networking technology to investigate their chemodiversity and uniqueness. We expect to discover structurally novel compounds by modern chromatographic and spectroscopic means. The new natural products will be screened by antibacterial, antitumor, and anti-Alzheimer’s disease models to discover potent compounds. This project will pave a new way for exploiting marine uncultured microbial new resources, and to provide candidates for marine new drug discovery in our country.