Identification of Secondary Metabolites and Biosynthesis Pathways in A. nidulans

该项目的目标是通过化学方法确定40种次生代谢物及其 真菌nidulans能够产生的相应的生物合成基因簇。作为 这个多学科项目的化学成分，我们将使用化学技术来识别 到目前为止还不能在金黄色葡萄球菌中描述的化合物。基因组学时代呈现了一个完整的 确定新的治疗线索的新的令人兴奋的方法。传统天然产物药物发现 过去几十年的计划表明，曲霉等真菌物种一直是一种丰富的 针对多种疾病的化疗药物来源。几种曲霉菌的基因组研究 最近对物种进行了测序，有趣的是，基因组揭示了产生 令人惊讶的大范围的天然产品，其中许多目前尚不为人所知。更重要的是，这个物种 产生的化合物彼此之间截然不同，这表明有丰富的天然 尚未发现的产品。这一发现将反过来取决于操纵工具的进步 曲霉遗传学(项目1)和对曲霉次生代谢物规则的理解(项目1) 2)。我们的组成部分将包括分析由这两个亚组创造的曲霉突变株。此外 由于我们在聚酮合成酶和非核糖体合成酶方面的经验，我们将与这两者互动 设计实验来阐明这些目前未知的次生代谢物。 在实验方面，我们将分析由 Oakley组和Keller组使用我们的Thermofinnigan LCQ。将开发新的分离方法 已发现的次生代谢物及其用核磁共振解析的化学结构。

The goal of this Project is to chemically identify each of the 40+ secondary metabolites and their corresponding biosynthetic gene clusters that the fungus Aspergillus nidulans is capable of producing. As the chemical component of this multidisciplinary program project, we will use chemical techniques to identify the compounds that have thus far eluded characterization in A. nidulans. The era of genomics presents a whole new exciting approach for identifying new therapeutic leads. Traditional natural product drug discovery programs in the past few decades have demonstrated that fungi species such as Aspergillus have been a rich source of chemotherapeutic agents against a variety of diseases. The genomes of several Aspergillus species have recently been sequenced and interestingly the genomes revealed a potential to produce surprising large range of natural products many of which are currently unknown. More importantly the species produce compounds that are drastically different from each other suggesting that there is a wealth of natural products yet to be discovered. This discovery will in turn depend on advancements in tools manipulating Aspergillus genetics (Project 1) and understanding of Aspergillus secondary metabolite regulations (Project 2). Our component will involve analyzing the Aspergillus mutants created by the two subgroups. In addition because of our experience in polyketide synthase and nonribosomal synthetase, we will interact with the two subgroups to design experiments to elucidate these currently unknown secondary metabolites. Experimentally we will analyze secondary metabolites produced by A. nidulans strains provided by the Oakley group and Keller group using our Thermofinnigan LCQ. Methods will be developed to isolate newly discovered secondary metabolites and their chemical structures solved using NMR.