The dynamic architecture of the metabolic switch in Streptomyces coelicolor.

The dynamic architecture of the metabolic switch in Streptomyces coelicolor.
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DOI:
10.1186/1471-2164-11-10
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发表时间:
2010-01-06
期刊:
影响因子:
4.4
通讯作者:
Wellington EM
Wellington EM
中科院分区:
生物学2区
文献类型:
--
作者:
Nieselt K;Battke F;Herbig A;Bruheim P;Wentzel A;Jakobsen ØM;Sletta H;Alam MT;Merlo ME;Moore J;Omara WA;Morrissey ER;Juarez-Hermosillo MA;Rodríguez-García A;Nentwich M;Thomas L;Iqbal M;Legaie R;Gaze WH;Challis GL;Jansen RC;Dijkhuizen L;Rand DA;Wild DL;Bonin M;Reuther J;Wohlleben W;Smith MC;Burroughs NJ;Martín JF;Hodgson DA;Takano E;Breitling R;Ellingsen TE;Wellington EM

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在发酵罐培养的生命周期中,土壤细菌S. coelicolor经历了一个主要的代谢转换,从指数增长到抗生素生产。我们使用专门设计的Affymetrix基因芯片和高分辨率的发酵剂生长样本时间序列研究了这种转换过程中的基因表达模式。令人惊讶的是,我们发现代谢开关实际上由多个精心安排的开关事件组成。在经典定义的从初级代谢到次级代谢的转换阶段之前,强烈连贯的基因簇已经显示出基因表达的剧烈变化。基因表达的主要开关只需要2小时,而抗生素生物合成基因的变化相对于代谢重排是延迟的。此外,形态发生基因的全球变异表明,在决定阶段,细胞分化途径的参与导致了抗生素生物合成的承诺。我们的研究首次提供了对S. coelicolor主要代谢开关期间和之前的复杂早期调控事件序列的详细见解,这将成为未来在生物技术环境下工程抗生素生产尝试的起点。
During the lifetime of a fermenter culture, the soil bacterium S. coelicolor undergoes a major metabolic switch from exponential growth to antibiotic production. We have studied gene expression patterns during this switch, using a specifically designed Affymetrix genechip and a high-resolution time-series of fermenter-grown samples. Surprisingly, we find that the metabolic switch actually consists of multiple finely orchestrated switching events. Strongly coherent clusters of genes show drastic changes in gene expression already many hours before the classically defined transition phase where the switch from primary to secondary metabolism was expected. The main switch in gene expression takes only 2 hours, and changes in antibiotic biosynthesis genes are delayed relative to the metabolic rearrangements. Furthermore, global variation in morphogenesis genes indicates an involvement of cell differentiation pathways in the decision phase leading up to the commitment to antibiotic biosynthesis. Our study provides the first detailed insights into the complex sequence of early regulatory events during and preceding the major metabolic switch in S. coelicolor, which will form the starting point for future attempts at engineering antibiotic production in a biotechnological setting.
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