Metabolic reprogramming and stress mitigation of Chlamydomonas reinhardtii using protective metal-phenolic networks

Abstract Single-cell encapsulation is widely used in biotechnology to protect highly sensitive living cells from environmental stress. However, the impact of encapsulation on biological function and metabolism remains rarely explored despite its importance for understanding stress response and modulating the production of valuable metabolites. Herein, we show that coating individual cells with protective metal-phenolic networks not only improves survival against stress, but also modifies cellular metabolism. Importantly, this encapsulation technique induces a reversible state of quiescence, which enables accumulation of high-energy-density compounds through selective nutrient diffusion and the resulting carbon flux redistribution. Specifically, light exposure favors the accumulation of nearly eightfold higher starches, while incubation in darkness leads to twofold higher lipid accumulation compared to native cells. This metabolic engineering approach via individual cell encapsulation expands the cell editing toolbox and will facilitate applications in synthetic biology, bioengineering, and cell-based therapeutics. Competing Interest Statement The authors have declared no competing interest. Footnotes Corrected a duplicated sentence in the abstract and fixed minor typographical errors.