Acetate as a metabolic booster for glucose-based bioproduction in Escherichia coli

Abstract Escherichia coli , a key workhorse in industrial biotechnology, is commonly grown on glucose, which supports rapid growth but leads to acetate overflow, which instead inhibits growth, diverts carbon from the production pathway, and reduces productivity. Recent studies suggest that acetate may also have beneficial effects in glucose-grown E. coli , but its potential in bioprocesses remains unexplored. In this study, we systematically investigated acetate’s impact on bioproduction using a kinetic model of glucose and acetate metabolism in E. coli . The model predicts that acetate can enhance bioproduction in glucose-grown E. coli through three mechanisms: (i) by minimizing acetate overflow, thereby reducing carbon loss, (ii) by increasing acetyl-CoA levels, thereby boosting the biosynthetic flux of acetyl-CoA-derived compounds, and (iii) by promoting biomass accumulation, thus improving overall productivity. We experimentally validated the predictions of the model for mevalonate and 3-hydroxypropionate production, where acetate supplementation increased productivity by 117% and 34%, respectively. Our findings provide a valuable framework for optimizing E. coli -based bioprocesses and highlight acetate’s underutilized potential in biotechnology. By leveraging acetate from waste streams as a metabolic booster, this approach could contribute to more sustainable and environmentally friendly bioprocesses. Highlights - A kinetic model was used for rational optimization of E. coli -based bioprocesses - Acetate can enhance growth and production of acetyl-CoA-derived bioproducts - Model predictions were validated for mevalonate and 3-hydroxypropionate production - Acetate can be used as a metabolic booster for glucose-based bioproduction in E. coli