A Synthetic Biology Toolbox for Natural Product Discovery from Actinomycetes

描述(由申请人提供)：最近的大规模合成生物学努力表明，现在可以系统地设计生物合成途径和中央代谢系统，为商品化学品和生物燃料市场生产大量的天然产品。在这些努力中开发的工具，包括模块化DNA构建库、用于途径平衡的已定义启动子和快速基因工程方法，旨在以高效的方式系统地解决异源天然产物的转录、翻译和生产问题。然而，这些先前的努力主要集中在缺乏复杂次生代谢物的宿主上，例如多酮和非核糖体肽。我们正在开发一系列合成生物学工具，专门设计富含细菌的细菌属。 为了获得在隐蔽基因簇中编码的代谢物，对天然产品进行了研究。这套工具有可能通过系统地提供获取由这一未开发的化学多样性的重要来源编码的分子的途径来重振天然产品的发现工作。

DESCRIPTION (provided by applicant): Recent large-scale synthetic biology efforts have demonstrated that it is now possible to systematically engineer biosynthetic pathways and central metabolic systems to produce massive quantities of natural products for the commodity chemicals and biofuels markets. The tools developed during these efforts, which include libraries of modular DNA constructs, defined promoters for pathway balancing, and rapid genetic engineering methods, were designed to systematically address the transcription, translation, and production of heterologous natural products in a highly efficient manner. These previous efforts, however, have focused primarily on hosts that are devoid of complex secondary metabolites such as polyketides and non-ribosomal peptides. We are developing a series of synthetic biology tools to specifically engineer bacterial genera that are rich producers of natural products in order to gain access to the metabolites encoded in cryptic gene clusters. This set of tools has the potential to revitalize natural product discovery efforts by systematicaly providing access to the molecules encoded by this important source of untapped chemical diversity.