Mining the Aspergillus nidulans Secondary Metabolome

该计划项目的主要目标是利用基因组学，分子遗传学和天然产物化学的协同组合，以识别和纯化丝状真菌构巢曲霉的潜在有用的次级代谢产物。最近发表的三种曲霉属的基因组测序结果表明，这些物种具有惊人数量的次级代谢途径，这些途径是新的和有用的天然产物的潜在来源。大多数A. nidulans的次级代谢途径目前尚不清楚，三个研究小组将共同努力，以鉴定和纯化A. nidulans。项目#1由俄亥俄州州立大学的Berl奥克利博士领导，总体PI，他将开发系统性启动子交换和系统性基因破坏的工具， 通过有针对性的基因替换。一个完整的A.将产生携带关键的非核糖体肽合成酶或聚酮化合物合成酶基因缺失的构巢菌菌株。项目#2由威斯康星州大学的Nancy Keller博士领导，他将专注于染色质突变体，以增强最低表达簇的产生并激活“沉默”簇。项目#3由南加州大学的Clay Wang博士领导，他将专注于中学的隔离和表征。 A.代谢产物来自奥克利和凯勒实验室的构巢菌菌株。总之，这项多学科合作将发现构巢曲霉的新次级代谢产物，并开发可用于挖掘其他真菌物种的次级代谢组以获得有价值的天然产物的方法。

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.