Lanthanum (La³⁺)-associated metabolic shifts in Euglena gracilis: A sustainable biorefinery strategy for enhanced paramylon production

Euglena gracilis is a promising chassis for sustainable microalgal biorefineries, particularly for producing paramylon (β-1,3-glucan). However, commercial viability is often limited by several bioprocessing challenges, among which the physiological growth-storage trade-off, which limits resource use efficiency. Systematically screened 16 rare earth elements (REEs) and identified Lanthanum (La³⁺) as an effective metabolic regulator. Integrating physiological phenotyping and untargeted metabolomics, we explored how La³⁺ (35 µmol/L) enhances mixotrophic productivity. Results suggest La³⁺ treatment is associated with alleviation competition between cell division and storage. It exhibits a concurrent enhancement of growth and storage, accelerating specific growth rates while boosting intracellular paramylon by 22.04%. Crucially, this altered metabolic state is visually correlated with a population shift toward a distinct ovoid morphotype, offering a potential morphological indicator for process monitoring. Mechanistically, we propose a hypothesis based on observed static metabolic changes. Metabolomic profiling revealed putative lipid-associated metabolic shifts, including the pronounced elevation of a specific HETE isomer (upregulated 578-fold) and lysophosphatidic acids. In parallel, we observed the concurrent enrichment of static intermediate pools within the TCA and glyoxylate cycles, alongside a 5.53-fold surge in Acetyl-CoA levels. Rather than an established mechanistic chain, we hypothesize that these collective metabolic alterations might be associated with altered carbon partitioning, potentially providing the requisite energy and precursors to simultaneously support both rapid cell proliferation and distinct polysaccharide synthesis. This study establishes a scalable metabolic engineering strategy using REEs, offering an effective processing method to improve resource use efficiency and synergistically enhance yields in sustainable microalgal biorefineries. • La³⁺ enhances sustainable Euglena biorefineries via associated metabolic shifts. • Modulating the growth-storage trade-off correlates with a 22% paramylon boost. • Putative lipid shifts correlate with enriched TCA and glyoxylate intermediate pools. • The ovoid morphotype offers a visual indicator for bioprocess monitoring.