Single-atom iron delivered by nanoliposomes boosts biomass accumulation and energy-rich metabolite production in Chlamydomonas reinhardtii

NLCs stabilize Fe 1 /NC to prevent aggregation in culture media for over 7 days. • NLCs bypass the cytomembrance barrier to enable efficient Fe 1 /NC cellular. • Fe 1 /NC-NLCs increase biomass, lipid and carbohydrate accumulation. • Fe 1 /NC-NLCs scavenge ROS, elevate POD activity by 35% and CAT activity by 200%. • Fe 1 /NC-NLCs regulate related genes and significantly modulate carbon flux. To overcome the inherent bottlenecks of low metabolic efficiency and biomass yield in microalgal biomanufacturing, this study presents an innovative strategy using single-atom iron dispersed within nanoliposomes (Fe 1 /NC-NLCs). Traditional metal additives often suffer from severe aggregation and toxicity. Here, nanoliposomes not only prevented single-atom iron aggregation but also ensured superior aqueous dispersion and effective cellular uptake by Chlamydomonas reinhardtii ( C. reinhardtii ). Functioning as highly dispersed bioactive regulators rather than conventional catalysts, these composites profoundly rewired cellular metabolism. Consequently, upon continuous treatment with an optimized dosage of 8.62 g/L Fe 1 /NC-NLCs over a 7-day cultivation period, microalgal biomass concentration significantly increased from 1.27 to 1.50 g/L. Crucially, the treatment orchestrated a metabolic shift toward energy-rich storage compounds, achieving carbohydrate and lipid yields of 203.35 mg/(L·d) and 613.36 mg/(L·d), which were approximately 2.2-fold and 2.0-fold higher than the control, respectively. Mechanistically, Fe 1 /NC-NLCs maintained cellular redox homeostasis by amplifying endogenous antioxidant enzymes, specifically POD and CAT, whose activities reached 646.8 U/g and 224.3 U/g, respectively. Transcriptomic analysis further revealed that this physiological enhancement was coupled with the upregulation of nitrogen assimilation, pyruvate metabolism, and amino acid biosynthesis. Ultimately, by efficiently coordinating carbon and nitrogen fluxes, this novel nanoplatform maximizes microalgal bioproduction, demonstrating profound potential for sustainable biofuel and biochemical applications. Download: Download high-res image (177KB) Download: Download full-size image