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作 者:Xiaoli Yan Benyin Zhang Wenya Tian Qi Dai Xiaoqin Zheng Ke Hu Xinxin Liu Zixin Deng Xudong Qu
机构地区:[1]Key Laboratory of Combinatorial Biosynthesis and Drug Discovery Ministry of Education,School of Pharmaceutical Sciences,Wuhan University,China [2]State Key Laboratory of Plateau Ecology and Agriculture,Qinghai University,China [3]Jiangshu National Synergetic Innovation Center for Advanced Materials(SICAM),China
出 处:《Synthetic and Systems Biotechnology》2018年第1期76-80,共5页合成和系统生物技术(英文)
基 金:This work was financially supported by NSFC(Nos.31322002,31500049 and 31270119,81760633);the State Key Laboratory of Microbial Metabolism(MMLKF17-08).
摘 要:Natural product discovery is pivot for drug development,however,this endeavor is often challenged by the wide inactivation or silence of natural products biosynthetic pathways.We recently developed a highly efficient approach to activate cryptic/silenced biosynthetic pathways through augmentation of the phosphopantetheinylation of carrier proteins.By applying this approach in the Streptomyces alboniger NRRL B-1832,we herein identified three cryptic nucleosides products,including one known puromycin A and two new derivatives(puromycin B and C).The biosynthesis of these products doesn't require the involvement of carrier protein,indicating the phosphopantetheinyl transferase(PPtase)indeed plays a fundamental regulatory role in metabolites biosynthesis.These results demonstrate that the PPtasebased approach have a much broader effective scope than the previously assumed carrier proteininvolving pathways,which will benefit future natural products discovery and biosynthetic studies.
关 键 词:PUROMYCIN Phosphopantetheinyl transferase Gene activation Streptomyces alboniger Genome mining
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