In silico cell factory design driven by comprehensive genome-scale metabolic models: development and challenges

Jiangong Lu; Xinyu Bi; Yanfeng Liu; Xueqin Lv; Jianghua Li; Guocheng Du; Long Liu

doi:10.1007/s43393-022-00117-4

Systems Microbiology and Biomanufacturing ›› 2022, Vol. 3 ›› Issue (2) : 207-222. DOI: 10.1007/s43393-022-00117-4

Review

In silico cell factory design driven by comprehensive genome-scale metabolic models: development and challenges

Jiangong Lu¹^,² ,
Xinyu Bi¹^,² ,
Yanfeng Liu¹^,² ,
Xueqin Lv¹^,² ,
Jianghua Li¹^,²^,^e ,
Guocheng Du¹^,² ,
Long Liu¹^,²^,^g

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Abstract

Genome-scale metabolic models (GEMs) have been widely used to design cell factories in silico. However, initial flux balance analysis only considers stoichiometry and reaction direction constraints, so it cannot accurately describe the distribution of metabolic flux under the control of various regulatory mechanisms. In the recent years, by introducing enzymology, thermodynamics, and other multiomics-based constraints into GEMs, the metabolic state of cells under different conditions was more accurately simulated and a series of algorithms have been presented for microbial phenotypic analysis. Herein, the development of multiconstrained GEMs was reviewed by taking the constraints of enzyme kinetics, thermodynamics, and transcriptional regulatory mechanisms as examples. This review focused on introducing and summarizing GEMs application tools and cases in cell factory design. The challenges and prospects of GEMs development were also discussed.

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Jiangong Lu, Xinyu Bi, Yanfeng Liu, Xueqin Lv, Jianghua Li, Guocheng Du, Long Liu. In silico cell factory design driven by comprehensive genome-scale metabolic models: development and challenges. Systems Microbiology and Biomanufacturing, 2022, 3(2): 207‒222 https://doi.org/10.1007/s43393-022-00117-4

Funding

Key Research and Development Program of China,(2020YFA0908300); National Natural Science Foundation of China,(32021005); Fundamental Research Funds for the Central Universities,(Fundamental Research Funds for the Central Universities)