Metabolic engineering strategies for astaxanthin biosynthesis in non-native microbial cell factories

Astaxanthin, a C₄₀ carotenoid with exceptional antioxidant, anti-inflammatory, and anticancer physiological activities, has experienced surging market demand across cosmeceutical, food, and pharmaceutical industries. Traditional astaxanthin production methods have critical limitations, including high costs, significant environmental impact, limited scalability, and stereochemical inadequacies, underscoring the urgent need for alternative production platforms. Metabolic engineering of industrial microorganisms provides a paradigm-shifting solution, leveraging rapid growth, genetic tractability, scalable fermentation, and climate-independent production to achieve sustainable, cost-effective astaxanthin biosynthesis. In this review, we comprehensively review the metabolic engineering strategies employed in non-native astaxanthin producers for higher production of astaxanthin, including directing carbon fluxes toward astaxanthin productivity, balanced expression of either engineered or non-engineered enzymes, their compartmentalization, morphology, and membrane engineering, cofactors, and precursor optimization. Additionally, we highlight emerging technologies aimed at overcoming current bottlenecks faced by non-native producers to advance their industrial applicability and further boost astaxanthin yields toward industrial competitiveness.