ApbZIP2-mediated enhancement of lipid productivity supports sustainable plant-based omega-3 biomanufacturing

Rising demand for ω-3 fatty acids intensifies pressure on marine fish stocks, driving demand for sustainable alternatives. Microalgae offer a land-independent platform, but traditional induction methods compromise lipid quality and consume resources, limiting their alignment with green manufacturing principles. Through integrated bioinformatic screening and molecular validation of Auxenochlorella protothecoides, an S-type basic leucine zipper transcription factor, ApbZIP2, was characterized as a pivotal enhancer of lipid productivity by transcriptionally reprogramming carbon allocation to concurrently boost lipid accumulation and reduce carbohydrate deposition. An engineered strategy combining ApbZIP2 overexpression with improved fermentation processes yielded a lipid productivity of 594.65 mg/(L·d), a 4.98-fold increase compared to the wild-type under original conditions, without distorting native fatty acid profiles, retaining approximately 70% unsaturated fatty acids including 39% ω-3 species, a physiologically favorable ω-6/ω-3 ratio (1.10), and robust anti-atherogenic and anti-thrombogenic indices. The work provides a foundational framework for sustainable ω-3 manufacture, mitigating strain on marine ecosystems.