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

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 under control various regulatory mechanisms. In recent years, by introducing enzymology, thermodynamics, other multiomics-based constraints into GEMs, state cells different conditions was more simulated a series algorithms presented for microbial phenotypic analysis. Herein, development multiconstrained GEMs reviewed taking enzyme kinetics, transcriptional mechanisms as examples. This review focused on summarizing application tools cases factory design. The challenges prospects were also discussed.