Genetic materials from marine derived microorganisms as new anticancer leads

这是由菲尔·克鲁斯（加州大学圣克鲁斯分校化学与生物化学系）领导的5号实验室项目。该项目题为“海洋微生物遗传材料作为新的抗癌领导者”，将探索组合生物合成和组合生物学中潜在的海洋衍生材料。一个培养的海洋微生物库将用于组合生物学。在组合生物合成工作中，一组7个先导结构是有待探索的候选物。这两种方法的目标都是发现新的生物活性天然产物抗癌化疗先导物。该项目的目标分为以下几类：1。建立海洋微生物文库，作为组合生物学的基因组DNA来源。2. 以海洋海绵来源的真菌、黏菌和放线菌为基础建立微生物文库。3. 通过探索作为UCSC文库化合物来源的生物体的基因组DNA，特别是latrunculin a和swinholide a，进行组合生物合成研究。利用微生物萃取物的机制依赖性分析来评价组合生物学和生物合成的进展。5. 利用高通量筛选技术从活性提取物中高效分离次生代谢物。6. 通过重组微生物的再培养进行大规模再分离，以便在我们的财团资助的临床前模型中进一步研究。7. 完成活性化合物的总结构解析。8. 获得重要的新活性化合物的患者覆盖率。

This is Laboratory Program #5 led by Phil Crews (Department of Chemistry and Biochemistry at the U.C. Santa Cruz). The project entitled, Genetic Materials from marine-Derived Microorganisms as New Anti- cancer Leaders, will explore the potential marine derived materials in combinatorial biosynthesis and combinatorial biology. A library of cultured marine-derived microorganisms will be used for combinatorial biology. A group of seven lead structures are candidates to be explored in combinatorial biosynthetic work. The goal of both approaches is to discover new bioactive natural product anti-cancer chemotherapy leads. The aims of the project are divided into categories as follows: 1. To construct a library of marine-derived microorganisms as a source of genomic DNA for combinatorial biology. 2. To base the microorganism library on marine sponge-derived: fungi, myxobacteria and actinomycetes. 3. To engage in combinatorial biosynthesis studies by exploring genomic DNA from organisms that are a source of UCSC library compounds, especially latrunculin A and swinholide A. 4. To employ mechanism-dependent assays on microorganism extracts to assess the progress of combinatorial biology and biosynthesis. 5. To efficiently isolate secondary metabolites from active extracts guided by high throughput screens. 6. To initiate scale-up reisolation by reculture of recombinant microorganisms for further study in the preclinical models of our consortium grant. 7. To complete the total structure elucidation of active compounds. 8. To obtain patient coverage for important new active compounds.