中文摘要
海洋放线菌中的非核糖体肽类天然产物是药用功能分子的重要来源,现在已有salinosporamide A和thiocoraline分别进入FDA抗癌一期临床研究和临床前评价。然而,当前对海洋放线菌非核糖体肽类天然产物的探索发现还有巨大的潜力可挖,对此类天然产物的生物合成研究更是较少开展。本课题拟通过基于PCR筛选的基因组挖掘技术和对小规模发酵提取物的质谱(MS)等化学筛查技术,对海洋(主要是我国南海海域)放线菌中的非核糖体肽类天然产物进行探索发现。在此基础上开展其生物合成研究,重点对其生物合成途径中、对化合物结构复杂性和生物活性重要的肽骨架修饰蛋白的催化功能进行研究。通过本课题的研究,将弥补国内外对海洋放线菌非核糖体肽类天然产物相关研究的不足,为我国开发具临床药用价值的创新药物及推动我国海洋资源的开发利用做出贡献。
英文摘要
The nonribosomal peptide natural products produced from marine actinomycetes are important sources of bioactive molecules. Two of these nonribosomal peptides, salinosporamide A and thiocoraline, have been in the FDA phase-I and preclinical development for anticancer drugs, respectively. However, only a few marine actinomycetes-produced nonribosomal peptides have been discovered, and little biosynthetic research has been done for these natural products. In this study, we plan to (1) discover more nonribosomal peptides from marine (mainly the south China sea) actinomycetes using PCR-based genome mining and MS-based chemical investigation; and (2) carry out the biosynthetic research for these natural products, especially characterizing the functions of peptide skeleton-modifying proteins, which contribute a lot to the chemical complexity and bioactivity. These studies will contribute to the discovery and biosynthetic research of marine actinomycetes-produced nonribosomal peptides, and to our country's novel clinical drug discovery and marine sources exploitation.
