This study presents a compelling advancement in sustainable biopolymer production by demonstrating how cassava-derived dextrose can be efficiently converted into polyhydroxybutyrate (PHB) through a model-informed fed-batch strategy. By integrating genome-scale flux balance analysis with precisely timed pulse-feeding regimes, the authors shift Cupriavidus necator metabolism from biomass growth toward enhanced carbon storage. The work reveals that late-stage, carbon-only feeding under nitrogen-limited conditions significantly boosts PHB accumulation, achieving up to ~50% of cell dry weight, compared to substantially lower yields under growth-favoring regimes. This approach transforms fed-batch fermentation from an empirical process into a predictive, controllable system, enabling deliberate optimization of intracellular carbon flux. From an industrial perspective, the strategy reduces substrate wastage, improves polymer yield, and simplifies downstream processing, thereby strengthening process economics. Coupled with the use of low-cost cassava feedstocks, this framework offers a scalable and regionally adaptable pathway toward commercially viable, biodegradable plastics. Moreover, the integration of digital modeling with fermentation operations establishes a transferable blueprint for next-generation biomanufacturing platforms, with strong implications for startup innovation, IP development, and global deployment in emerging bioeconomies.

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