Astaxanthin from Haematococcus pluvialis and Chromochloris zofingiensis: Biosynthetic Pathways, Engineering Strategies, and Industrial Prospects

Astaxanthin, a high-value keto-carotenoid with potent antioxidant and health-promoting properties, has gained global attention as a sustainable nutraceutical and biotechnological product. The green microalgae <i>Haematococcus pluvialis</i> and <i>Chromochloris zofingiensis</i> represent two promising natural producers, yet they differ markedly in physiology, productivity, and industrial scalability. This review provides a focused comparative analysis of these two species, emphasizing their quantitative performance differences. <i>H. pluvialis</i> can accumulate astaxanthin up to ~3-5% of dry biomass but typically reaches biomass densities of only 5-10 g L^-1, whereas <i>C. zofingiensis</i> achieves ultrahigh biomass concentrations of 100-220 g L^-1 under heterotrophic fed-batch fermentation, although its astaxanthin content is much lower (~0.1-0.5% DW). While <i>H. pluvialis</i> remains the benchmark for natural astaxanthin due to its exceptionally high cellular content, its thick cell wall, slow growth, and strict phototrophic requirements impose major cost and operational barriers. In contrast, <i>C. zofingiensis</i> exhibits rapid and flexible growth under heterotrophic, mixotrophic, or phototrophic conditions and can achieve ultrahigh biomass in fermentation, though its ketocarotenoid flux and astaxanthin accumulation remain comparatively limited. Meanwhile, a rapidly growing patent landscape demonstrates global technological competition, with major portfolios emerging in China, the United States, and Europe, spanning chemical synthesis, microbial fermentation, algal metabolic engineering, and high-density cultivation methods. These patents reveal clear innovation trends-ranging from solvent-free green synthesis routes to engineered microalgae and yeast chassis for enhanced astaxanthin production-which increasingly shape industrial development strategies. By synthesizing recent advances in metabolic engineering, two-stage cultivation, and green extraction technologies, this review identifies key knowledge gaps and outlines a practical roadmap for developing next-generation astaxanthin biorefineries, with an emphasis on scalable production and future integration into broader biorefinery frameworks. The findings aim to guide future research and provide actionable insights for scaling sustainable, cost-effective production of natural astaxanthin.