Development and Applications of a Kinetic Model for Resveratrol Production in Escherichia coli Cell Factories

Resveratrol is a compound with significant medical and nutraceutical benefits, offering great economic value due to its diverse therapeutic effects. Traditional production of resveratrol from plants is limited by slow growth rates and challenges in maintaining consistent purity. Heterologous production in microbial systems has emerged as a promising alternative. Here, we developed a chemical kinetic model to improve our understanding of the factors influencing resveratrol production in engineered Escherichia coli. While computational models have been widely used in microbial cell factories, most focus on flux balance analyses, which are useful for identifying gene knockout targets and optimizing media. However, these models often overlook enzyme expression levels and kinetic parameters, which are critical for optimizing production. Our model specifically incorporates these parameters, providing a more detailed understanding of how changes in enzyme kinetics and expression affect production outcomes. Our model successfully explained experimental observations from our engineered E. coli strain, and other reported results in the literature. Despite limited data, we demonstrate that the model narrows down possible ranges for key kinetic parameters such as stilbene synthase expression level, especially when resveratrol production is high. Further validation and refinement of the model will enhance its predictive power, aiding the design of future microbial cell factories for resveratrol and other polyphenolic compounds. HIGHLIGHTS We built a kinetic model for resveratrol production in engineered coli. The model predicts possible ranges of resveratrol outputs and intermediate metabolites. Experimental results help narrow down possible ranges of intermediate metabolites and enzyme expression levels. Higher resveratrol productivity corresponds to narrower ranges of possible enzyme expression levels. GRAPHICAL ABSTRACT