Engineering Microalgae for Enhanced Astaxanthin Production: Integrating Metabolic Pathways and Nano-Biotechnologies.

Astaxanthin is a high-value metabolite with substantial market demand, owing to its potent antioxidant activity and diverse health benefits. Microalgae are considered the primary producers of esterified astaxanthin, yet their industrial-scale cultivation is constrained by low productivity, stress-dependent induction, and challenges in metabolic engineering. This review examines strategies to enhance microalgae-derived esterified astaxanthin production through nanoformulation and modulation of metabolic pathways. We highlight that precise, efficient, and multiplexed genetic modifications of the carotenoid biosynthetic pathway can significantly increase astaxanthin accumulation. Downregulation of competing metabolic routes further improves astaxanthin yields. Additionally, targeted engineering of acyltransferases and lipid metabolism regulators enhances astaxanthin esterification, thereby improving its intracellular stability against oxidative degradation. Modifying lipid metabolism also redirects metabolic fluxes toward altered fatty acid saturation in stored lipids, which increases the bioavailability of esterified astaxanthin. The integration of nanoparticles into cultivation systems represents another promising approach, facilitating improved nutrient delivery and light management, and consequently boosting astaxanthin production. However, the application of genetic engineering and nanotechnology faces challenges such as biosafety legislation, regulatory approval processes, and potential ecological impacts. A synergistic combination of both approaches may help overcome these limitations and maximize astaxanthin production from microalgae.