BioModelsapplication/xmlhttps://www.ebi.ac.uk/biomodels/model/download/MODEL2506160002?filename=Gosselin2025_Ecoli_bioproduction_sensitive.xmlprimaryOK200MillardNon-curatedordinary differential equation modelL2V4https://www.ebi.ac.uk/biomodels/MODEL2506160002falseBioModelsSBMLModelsGosselin2025 Ecoli bioproduction sensitiveMODEL2506160002Thomas Gosselin-Monplaisir, Denis Jallet, Erwana Harscoet, Uttenweiler-Joseph, Stéphanie HeuxThomas Gosselin-Monplaisir10.1101/2025.06.17.659982, Escherichia coli, a key workhorse in industrial biotechnology, is commonly grown on glucose, which supports rapid growth but leads to acetate overflow. Acetate has long been regarded as a toxic by-product, known to divert carbon away from production pathways, inhibit cellular growth, and reduce 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.. null, null. Toulouse Biotechnology Institutepierre.millard@insa-toulouse.fr10.1101/2025.06.17.659982INRAEallergic reaction, sensitive., sensitivityS-acetate, allergic reaction, CoA, Acetyl, Coenzyme A, Acetyl-CoA, Acetyl CoA, sensitivity, sensitive, DOI, doi.falseGosselin2025 - Ecoli_bioproduction_sensitiveKinetic model for bioproduction via an acetyl-CoA sensitive pathway, as detailed in DOI 10.1101/2025.06.17.659982.2025-06-232025-06-232025-06-16MODEL2506160002MODEL250616000210.1101/2025.06.17.659982