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Saccharomyces cerevisiae phenotypes can be predicted by using constraint-based analysis of a genome-scale reconstructed metabolic network

机译:酿酒酵母的表型可以通过使用基于约束的基因组规模的重构代谢网络的分析来预测

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摘要

Full genome sequences of prokaryotic organisms have led to reconstruction of genome-scale metabolic networks and in silico computation of their integrated functions. The first genome-scale metabolic reconstruction for a eukaryotic cell, Saccharomyces cerevisiae, consisting of 1,175 metabolic reactions and 733 metabolites, has appeared. A constraint-based in silico analysis procedure was used to compute properties of the S. cerevisiae metabolic network. The computed number of ATP molecules produced per pair of electrons donated to the electron transport system (ETS) and energy-maintenance requirements were quantitatively in agreement with experimental results. Computed whole-cell functions of growth and metabolic by-product secretion in aerobic and anaerobic culture were consistent with experimental data, and thus mRNA expression profiles during metabolic shifts were computed. The computed consequences of gene knockouts on growth phenotypes were consistent with experimental observations. Thus, constraint-based analysis of a genome-scale metabolic network for the eukaryotic S. cerevisiae allows for computation of its integrated functions, producing in silico results that were consistent with observed phenotypic functions for ≈70–80% of the conditions considered.
机译:原核生物的全基因组序列已导致基因组规模的代谢网络的重建以及其整合功能的计算机计算。真核细胞酿酒酵母(Saccharomyces cerevisiae)的第一个基因组规模的代谢重建已经出现,它由1,175个代谢反应和733种代谢物组成。基于约束的计算机分析程序用于计算酿酒酵母代谢网络的属性。计算得出的每对捐赠给电子传输系统(ETS)的电子对产生的ATP分子数量和能量维持要求与实验结果一致。在有氧和厌氧培养中计算出的全细胞生长和代谢副产物分泌的全细胞功能与实验数据一致,从而计算了代谢转变过程中的mRNA表达谱。基因敲除对生长表型的计算结果与实验观察结果一致。因此,对酿酒酵母基因组规模的代谢网络进行基于约束的分析,可以计算其整合功能,产生计算机模拟结果,与观察到的表型功能一致(约70–80%)。

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