Strategies for Overcoming the Metabolic Trade-off in Microbial Cell Factories: Balancing Cell Growth and Product Synthesis

Microbial cell factories (MCFs) are pivotal to green biomanufacturing, yet their industrial application is often hindered by d metabolic trade-off^ -the inherent competition for resources between cell growth and target product synthesis. To address this issue, this review systematically summarizes existing literature and categorizes three types of balancing strategies for metabolic trade-offs. The "rigid” strategy employs irreversible approaches, such as gene knockout and overexpression, to reconstruct metabolic networks and forcibly redirect metabolic flux. While straightforward, it often leads to metabolic burden and reduced robustness. The ’flexible” strategy adopts spatiotemporal regulation of gene expression based on transcriptional dynamics to decouple growth from production. It offers greater adaptability but relies heavily on regulatory elements and requires high specificity in target selection. The ^u rigid-flexible hybrid” strategy capitalizes on the strengths of both: rigid engineering provides a high-yield framework, while flexible regulation enables precise optimization, thereby balancing synthesis efficiency and cellular fitness. Finally, this review anticipates that AI-assisted component design, multi-omics-driven metabolic network analysis, and intelligent control system implementation will accelerate the resolution of metabolic trade-offs. This will ultimately enable the precise, efficient, and intelligent construction of advanced microbial cell factories.