The construction of high-performance microbial cell factories (MCFs) is the centerpiece of biomanufacturing. However, the complex metabolic regulatory network of microorganisms poses great challenges for the efficient design and construction of MCFs. The genome-scale metabolic network models (GSMs) can systematically simulate the metabolic regulation process of microorganisms , providing effective guidance for the rapid design and construction of MCFs. In this review, we summarized the development status of 16 important industrial microbial GSMs, and further outline the technologies or methods that continuously promote high-quality GSMs construction from five aspects: I) Databases and modeling tools facilitate GSMs reconstruction; II) evolving gap-filling technologies; III) constraint-based model reconstruction; IV) advances in algorithms; and V) developed visualization tools. In addition, we also summarized the applications of GSMs in guiding metabolic engineering from four aspects: I) exploring and explaining metabolic features; II) predicting the effects of genetic perturbations on metabolism; III) predicting the optimal phenotype; IV) guiding cell factories construction in practical experiment. Finally, we discussed the development of GSMs, aiming to provide a reference for efficiently reconstructing GSMs and guiding metabolic engineering.

中文翻译：

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工业微生物代谢工程的基因组规模代谢网络模型：当前进展和未来前景

高性能微生物细胞工厂（MCF）的建设是生物制造的核心。然而，微生物复杂的代谢调控网络给MCF的高效设计和构建带来了巨大的挑战。基因组规模的代谢网络模型（GSM）可以系统地模拟微生物的代谢调控过程，为MCF的快速设计和构建提供有效指导。本文综述了16个重要工业微生物GSM的发展现状，并从五个方面进一步概述了持续推动高质量GSM建设的技术或方法：一）数据库和建模工具促进GSM重建； II) 不断发展的填补空白的技术； III) 基于约束的模型重建； IV）算法的进步； V) 开发可视化工具。此外，我们还从四个方面总结了GSMs在指导代谢工程中的应用：I）探索和解释代谢特征； II) 预测遗传扰动对新陈代谢的影响； III) 预测最佳表型；四）指导实际实验中的细胞工厂建设。最后，我们讨论了 GSM 的发展，旨在为高效重建 GSM 和指导代谢工程提供参考。