Targeted activation of silent natural product biosynthesis pathways by reporter-guided mutant selection----中国科学院微生物研究所

科研成果

论文题目:	Targeted activation of silent natural product biosynthesis pathways by reporter-guided mutant selection
作者:	Fang Guo, Sihai Xiang, Liyuan Li, Bin Wang, Johanna Rajas？rkk？, Kirsi Gr？ndahl-Yli-Hannuksela, Guomin Ai, Mikko Mets？-Ketel？, and Keqian Yang.
联系作者:
刊物名称:	Metabolic Engineering
期:	28
卷:	0
页:	134-142
年份:	2015
影响因子:	6.714
论文下载:	http://www.sciencedirect.com/science/article/pii/S1096717614001657
摘要:	The continuously increasing genome sequencing data has revealed numerous cryptic pathways, which might encode novel secondary metabolites with interesting biological activities. However, utilization of this hidden potential has been hindered by the observation that many of these gene clusters remain silent (or poorly expressed) under laboratory conditions. Here we present reporter-guided mutant selection (RGMS) as an effective and widely applicable method for targeted activation of silent gene clusters in the native producers. The strategy takes advantage of genome-scale random mutagenesis for generation of genetic diversity and a reporter-guided selection system for the identification of the desired target-activated mutants. It was first validated in the re-activation of jadomycin biosynthesis in Streptomyces venezuelae ISP5230, where high efficiency of activation was achieved. The same strategy was then applied to a hitherto unactivable pga gene cluster in Streptomyces sp. PGA64 leading to the identification of two new anthraquinone aminoglycosides, gaudimycin D and E.