Feist Adam M, Henry Christopher S, Reed Jennifer L, Krummenacker Markus, Joyce Andrew R, Karp Peter D, Broadbelt Linda J, Hatzimanikatis Vassily, Palsson Bernhard Ø
Department of Bioengineering, University of California San Diego, La Jolla, CA 92093, USA.
Mol Syst Biol. 2007;3:121. doi: 10.1038/msb4100155. Epub 2007 Jun 26.
An updated genome-scale reconstruction of the metabolic network in Escherichia coli K-12 MG1655 is presented. This updated metabolic reconstruction includes: (1) an alignment with the latest genome annotation and the metabolic content of EcoCyc leading to the inclusion of the activities of 1260 ORFs, (2) characterization and quantification of the biomass components and maintenance requirements associated with growth of E. coli and (3) thermodynamic information for the included chemical reactions. The conversion of this metabolic network reconstruction into an in silico model is detailed. A new step in the metabolic reconstruction process, termed thermodynamic consistency analysis, is introduced, in which reactions were checked for consistency with thermodynamic reversibility estimates. Applications demonstrating the capabilities of the genome-scale metabolic model to predict high-throughput experimental growth and gene deletion phenotypic screens are presented. The increased scope and computational capability using this new reconstruction is expected to broaden the spectrum of both basic biology and applied systems biology studies of E. coli metabolism.
本文介绍了大肠杆菌K-12 MG1655代谢网络的更新后的全基因组规模重建。这个更新后的代谢重建包括:(1)与最新的基因组注释和EcoCyc的代谢内容进行比对,从而纳入1260个开放阅读框(ORF)的活性;(2)对与大肠杆菌生长相关的生物质成分和维持需求进行表征和量化;(3)所包含化学反应的热力学信息。详细阐述了将这个代谢网络重建转化为计算机模拟模型的过程。引入了代谢重建过程中的一个新步骤,称为热力学一致性分析,其中检查反应与热力学可逆性估计的一致性。展示了全基因组规模代谢模型预测高通量实验生长和基因缺失表型筛选能力的应用。预计使用这个新重建所增加的范围和计算能力将拓宽大肠杆菌代谢的基础生物学和应用系统生物学研究的范围。