Mining the Aspergillus nidulans Secondary Metabolome

挖掘构巢曲霉次级代谢组

• 批准号: 8073833
• 负责人: BERL Ray OAKLEY
• 金额: $ 6.25万
• 依托单位: UNIVERSITY OF KANSAS LAWRENCE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8073833
• 关键词: Mining; Aspergillus; nidulans; Secondary; Metabolome

The primary goal of this Program Project is to use a synergistic combination of genomics, molecular genetics and natural products chemistry to identify and purify potentially useful secondary metabolites of the filamentous fungus Aspergillus nidulans. The recently published sequencing of genomes of three species of Aspergillus has revealed that these species have a surprisingly large number of secondary metabolism pathways that are potential sources of new and useful natural products. The products of most of the A. nidulans secondary metabolism pathways are currently unknown and the three research groups will work together towards the goal of identifying and purifying the product(s) of each of the secondary metabolism gene clusters in A. nidulans. Project #1 is headed by Dr. Berl Oakley at Ohio State University, the overall P.I., who will develop tools for systematic promoter exchanges and for the systematic disruption of genes through targeted gene replacements. A complete library of A. nidulans strains carrying deletions of key nonribosomal peptide synthetase or polyketide synthase genes will be created. Project #2 is headed by Dr. Nancy Keller at the University of Wisconsin, who will focus on chromatin mutants to enhance the production of minimally expressed clusters and to activate "silent" clusters. Project #3 is headed by Dr. Clay Wang at the University of Southern California, who will focus on isolation and characterization of secondary metabolites produced by A. nidulans strains from the Oakley and Keller laboratories. In summary, this multidisciplinary collaboration will discover new secondary metabolites from Aspergillus nidulans and develop methods that can be used to mine the secondary metabolomes of other species of fungi for valuable natural products.

该计划项目的主要目的是使用基因组学，分子遗传学和天然产品化学的协同组合来识别和净化丝状真菌曲霉的潜在有用的二级代谢物。最近发表的三种曲霉物质基因组的测序表明，这些物种具有令人惊讶的大量次级代谢途径，这些途径是新的和有用的天然产物的潜在来源。大多数A的产品。 Nidulans二级代谢途径目前尚不清楚，这三个研究小组将共同努力，以识别和净化A. nidulans中每个次级代谢基因簇的产物。 Project＃1由俄亥俄州立大学的Berl Oakley博士领导，他将开发用于系统启动子交流的工具，并系统地破坏基因 通过靶向基因置换。将创建一个完整的nidulans菌株的库，这些曲线含有关键的非核糖体肽合成酶或聚酮化合物合酶基因的缺失。项目＃2由威斯康星大学的南希·凯勒（Nancy Keller）博士领导，他将专注于染色质突变体，以增强最低表达的簇的生产并激活“无声”簇。项目＃3由南加州大学的克莱·王（Clay Wang）博士领导，他将专注于隔离和特征 来自奥克利和凯勒实验室的A. nidulans菌株产生的代谢产物。总而言之，这种多学科的合作将发现曲霉菌的新代谢产物，并开发可用于开采其他真菌种类的二级代谢组的方法，以作为有价值的天然产物。