Genetic materials from marine derived microorganisms as new anticancer leads

这是由Phil Crews(加州大学圣克鲁斯分校化学和生物化学系)领导的实验室计划#5。该项目名为《来自海洋衍生微生物的遗传物质作为新的抗癌领导者》，将探索海洋衍生材料在组合生物合成和组合生物学中的潜在应用。培养的海洋微生物文库将用于组合生物学。一组七个铅结构是组合生物合成工作中有待探索的候选结构。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。该项目的目标分为以下几类：1.构建海洋来源微生物文库，作为组合生物学基因组DNA的来源。2.以海绵中的真菌、粘细菌和放线菌为基础构建微生物文库。3.通过探索作为UCSC文库化合物来源的生物体的基因组DNA进行组合生物合成研究，特别是马兜铃素A和Swinholide A。4.对微生物提取物进行机制依赖的分析，以评估组合生物学和生物合成的进展。5.在高通量筛选的指导下，有效地从活性提取物中分离次生代谢物。6.通过重新培养重组微生物开始大规模再分离，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.获得重要新活性化合物的患者覆盖范围。

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.