Genetic materials from marine derived microorganisms as new anticancer leads

这是由Phil Crews（加州大学化学与生物化学系）领导的实验室计划#5。圣克鲁斯）。该项目名为“海洋微生物遗传物质作为新的抗癌领导者”，将探索潜在的海洋微生物在组合生物合成和组合生物学中的应用。一个培养的海洋来源微生物库将用于组合生物学。一组七个先导结构是组合生物合成工作中待探索的候选结构。这两种方法的目标是发现新的生物活性天然产物抗癌化疗线索。该项目的目标分为以下几类：1。构建海洋微生物文库作为组合生物学基因组DNA的来源。2.以海绵来源的真菌、粘细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，从事组合生物合成研究。4.利用微生物抽提物的机制依赖性分析来评估组合生物学和生物合成的进展。5. 通过高通量筛选从活性提取物中有效分离次级代谢产物。6. 通过重组微生物的再培养来启动扩大规模的再分离，以便在我们财团资助的临床前模型中进行进一步研究。7.完成活性化合物的全结构鉴定。8.为重要的新活性化合物获得患者保险。

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.