Escherichia coli is considered to be the best-known microorganism given the large number of published studies detailing its genes, its genome and the biochemical functions of its molecular components. This vast literature has been systematically assembled into a reconstruction of the biochemical reaction networks that underlie E. coli’s functions, a process which is now being applied to an increasing number of microorganisms. Genome-scale reconstructed networks are organized and systematized knowledge bases that have multiple uses, including conversion into computational models that interpret and predict phenotypic states and the consequences of environmental and genetic perturbations. These genome-scale models (GEMs) now enable us to develop pan-genome analyses that provide mechanistic insights, detail the selection pressures on proteome allocation and address stress phenotypes. In this Review, we first discuss the overall development of GEMs and their applications. Next, we review the evolution of the most complete GEM that has been developed to date: the E. coli GEM. Finally, we explore three emerging areas in genome-scale modelling of microbial phenotypes: collections of strain-specific models, metabolic and macromolecular expression models, and simulation of stress responses.

鉴于已发表的大量研究详细介绍了大肠杆菌的基因、基因组及其分子成分的生化功能，大肠杆菌被认为是最著名的微生物。这些大量文献已被系统地整合到对大肠杆菌功能基础的生化反应网络的重建中，这一过程现在正应用于越来越多的微生物。基因组规模的重建网络是有组织和系统化的知识库，具有多种用途，包括转换为解释和预测表型状态以及环境和遗传扰动后果的计算模型。这些基因组规模模型（GEM）现在使我们能够开发泛基因组分析，提供机制见解，详细说明蛋白质组分配的选择压力并解决应激表型。在这篇综述中，我们首先讨论 GEM 的整体发展及其应用。接下来，我们回顾一下迄今为止开发的最完整的 GEM：大肠杆菌GEM 的演变。最后，我们探索了微生物表型基因组规模建模的三个新兴领域：菌株特异性模型的集合、代谢和大分子表达模型以及应激反应的模拟。