A simple method to control glycolytic flux for the design of an optimal cell factory.

BACKGROUND: A microbial cell factory with high yield and productivity are prerequisites for an economically feasible bio-based chemical industry. However, cell factories that show a kinetic imbalance between glycolysis and product formation pathways are not optimal. Glycolysis activity is highly robust for survival in nature, but is not optimized for chemical production.

RESULTS: Here, we propose a novel approach to balance glycolytic activity with the product formation capacity by precisely controlling expression level of ptsG (encoded glucose transporter) through UTR engineering. For various heterologous pathways with different maximum production rates, e.g., n-butanol, butyrate, and 2,3-butanediol, glycolytic fluxes could be successfully modulated to maximize yield and productivity, while minimizing by-product formation in Escherichia coli.

CONCLUSIONS: These results support the application of this simple method to explore the maximum yield and productivity when designing optimal cell factories for value-added products in the fields of metabolic engineering and synthetic biology.