Max Planck Institute for Dynamics of Complex Technical Systems, Sandtorstrasse 1, 39106 Magdeburg, Germany.
Sci Rep. 2017 Jan 3;7:39647. doi: 10.1038/srep39647.
Genome-scale metabolic modeling has become an invaluable tool to analyze properties and capabilities of metabolic networks and has been particularly successful for the model organism Escherichia coli. However, for several applications, smaller metabolic (core) models are needed. Using a recently introduced reduction algorithm and the latest E. coli genome-scale reconstruction iJO1366, we derived EColiCore2, a model of the central metabolism of E. coli. EColiCore2 is a subnetwork of iJO1366 and preserves predefined phenotypes including optimal growth on different substrates. The network comprises 486 metabolites and 499 reactions, is accessible for elementary-modes analysis and can, if required, be further compressed to a network with 82 reactions and 54 metabolites having an identical solution space as EColiCore2. A systematic comparison of EColiCore2 with its genome-scale parent model iJO1366 reveals that several key properties (flux ranges, reaction essentialities, production envelopes) of the central metabolism are preserved in EColiCore2 while it neglects redundancies along biosynthetic routes. We also compare calculated metabolic engineering strategies in both models and demonstrate, as a general result, how intervention strategies found in a core model allow the identification of valid strategies in a genome-scale model. Overall, EColiCore2 holds promise to become a reference model of E. coli's central metabolism.
基因组规模代谢建模已成为分析代谢网络特性和能力的宝贵工具,尤其在模式生物大肠杆菌中取得了巨大成功。然而,对于某些应用,较小的代谢(核心)模型是必要的。我们使用最近引入的一种简化算法和最新的大肠杆菌基因组规模重建 iJO1366,推导出了大肠杆菌的中心代谢核心模型 EColiCore2。EColiCore2 是 iJO1366 的一个子网,保留了包括在不同底物上最优生长等预定义表型。该网络包含 486 种代谢物和 499 种反应,可进行基础模式分析,如果需要,可进一步压缩为包含 82 种反应和 54 种代谢物的网络,其解空间与 EColiCore2 相同。EColiCore2 与其基因组规模的父模型 iJO1366 的系统比较表明,中心代谢的几个关键特性(通量范围、反应重要性、生产包络)在 EColiCore2 中得以保留,同时忽略了生物合成途径中的冗余。我们还比较了两个模型中的计算代谢工程策略,并得出一个普遍的结论,即核心模型中的干预策略可以识别基因组规模模型中的有效策略。总体而言,EColiCore2 有望成为大肠杆菌中心代谢的参考模型。