土壤来源链霉菌Streptomyces sp. Gö66是一类对黑热病病原虫生长具有极强抑制活性的环庚三烯酚酮类化合物isatropolone的野生型产生菌。通过antiSMASH对其基因组序列进行初步分析，结果显示该菌的染色体上存在33个编码不同类型次级代谢产物的合成基因簇，除了已经明确的isatropolone的合成基因簇（II型聚酮）以外，其余绝大多数未知代谢产物的基因簇主要负责合成非核糖体肽类、I型、II型、III型聚酮类、萜类及羊毛硫肽类等化合物。本项目锁定了4个未知非核糖体肽基因簇作为主要研究目标，拟通过基因组挖掘的策略从Streptomyces sp. Gö66中获得4个或多个具有新颖结构和活性的非核糖体肽类及其衍生物，并通过体内或体外基因功能验证实验来阐明它们的生物合成机制，为后续通过人工设计和组合生物合成获得新颖活性肽类提供重要的功能元件。

Streptomyces is one of the most well-known prolific natural product producers, which can synthesizing antibacterial, antifungal, antitumor, antivirus and immunosuppressive agents. It has been reported that 2/3 of antibiotics used in clinic are from Streptomyces. With the great advances of high-throughput sequencing technology and bioinformatics, genome mining has become a very efficient strategy to tap novel natural products for drug discovery. ..Streptomyces sp. Gö66 was isolated from a soil sample collected from Göttingen in Germany, mainly producing isatropolones under normal lab condition. In our earlier study, we have sequenced the whole genome of strain Gö66 and identified isatropolone biosyntheitic gene cluster (BGC). However, antiSMASH analysis of the genome sequence revealed the presence of other 32 BGCs mostly encoding unknown secondary metabolites such as nonribosomal peptides (NRPs), Type I, II & III polyketides, terpenes, lantipeptides etc. ..In this proposal, we will focus on four unknown NRPS gene clusters and aim to obtain at least four new NRPs with diverse chemical structures and biological activities through genome mining approach. Moreover, their biosynthetic pathways will be investigated via in vivo and in vitro studies, which will provide important functional gene elements for synthesizing novel NRPs via artificial design and combinatorial biosynthesis.