角环素为放线菌中II型聚酮合酶产生的芳香聚酮类天然产物，具有极强的结构多样性和成为抗菌和抗癌药物的巨大潜力。与角环素结构类似的四环素类和蒽环类已有至少13个天然产物或其化学衍生物被FDA批准上市。海洋特有生境放线菌是新颖角环素类天然产物的宝库，然而目前国内外对海洋放线菌中角环素类天然产物的挖掘较少，生物合成的研究更是亟待开展。本课题拟通过PCR筛选结合对小规模发酵提取物的HPLC、MS等化学筛查技术，对来自于我国南海和东南沿海海域放线菌中的角环素类天然产物进行探索发现。在此基础上开展其生物合成的深入研究，重点对角环素类化合物中特殊结构片段的生物合成机制和新颖酶催化反应进行阐明，为生物合成的工程改造以产生成药性更好的天然产物类似物提供依据。通过本课题的研究，将弥补国内外对海洋放线菌角环素类天然产物相关研究的不足，为我国开发具有临床药用价值的创新药物先导物及海洋药用资源的开发利用做出贡献。

Angucyclines are aromatic polyketides exclusively discovered from actinomycetes and produced by type II polyketide synthases (PKS). This family of natural products possess high degree of structural diversity and are potential antibacterial and anticancer drugs. Angucyclines are structurally similar to tetracyclines and anthracyclines, and at least 13 of tetracyclines and anthracyclines have been approved by FDA as antibacterial and anticancer drugs. Marine actinomycetes are promising sources of new angucycline natural products. However, only a few angucyclines have been discovered from marine actinomycetes and their biosynthetic research is even less carried out. In this application, we discover new angucyclines from marine actinomycetes collected from South China Sea and southeast coast of China, on the basis of PCR screening method combined with HPLC and MS analyses. We further sequence the gene clusters of angucyclines, reveal the biosynthetic genesʹ functions based on gene deletion and chemical investigation of the mutants, and especially characterize the enzymatic reactions in key biosynthetic steps. The biosynthetic research will set stage for engineering of biosynthetic pathways to generate more "drug-like" angucycline analogues. These studies will contribute to the deep discovery and biosynthetic research of angucyclines from marine actinomycetes, and to novel clinical lead drugs development and marine sources exploitation.