Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA.
Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA.
Nat Rev Microbiol. 2020 Dec;18(12):731-743. doi: 10.1038/s41579-020-00440-4. Epub 2020 Sep 21.
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.
由于发表了大量详细描述大肠杆菌基因、基因组以及分子成分生化功能的研究，大肠杆菌被认为是最知名的微生物。这些大量的文献已经被系统地整合到一个重建的生化反应网络中，这个网络是大肠杆菌功能的基础，这个过程现在正在越来越多的微生物中应用。基于基因组规模的重建网络是有组织的和系统化的知识库，具有多种用途，包括转化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。这些基于基因组规模的模型（GEM）现在使我们能够开发泛基因组分析，提供机制见解，详细说明对蛋白质组分配的选择压力，并解决应激表型。在这篇综述中，我们首先讨论了 GEM 的总体发展及其应用。接下来，我们回顾了迄今为止开发的最完整的 GEM 的进化：大肠杆菌 GEM。最后，我们探讨了微生物表型基于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。
