Evolving perspectives on lutein production from microalgae - A focus on productivity and heterotrophic culture

Increased consumer awareness for healthier and more sustainable products has driven the search for naturally sourced compounds as substitutes for chemically synthesized counterparts. Research on pigments of natural origin, such as carotenoids, particularly lutein, has been increasing for over three decades. Lutein is recognized for its antioxidant and photoprotective activity. Its ability to cross the blood-brain barrier allows it to act at the eye and brain level and has been linked to benefits for vision, cognitive function and other conditions. While marigold flower is positioned as the only crop from which lutein is extracted from and commercialized, microalgae are proposed as an alternative with several advantages over this terrestrial crop. The main barrier to scaling up lutein production from microalgae to the commercial level is the low productivity compared to the high costs. This review explores strategies to enhance lutein production in microalgae by emphasizing the overall productivity over lutein content alone. Evaluation of how culture parameters, such as light quality, nitrogen sufficiency, temperature and even stress factors, affect lutein content and biomass development in batch phototrophic cultures was performed. Overall, the total lutein production remains low under this metabolic regime due to the low biomass productivity of photosynthetic batch cultures. For this reason, we describe findings on microalgal cultures grown under different metabolic regimes and culture protocols (fed-batch, pulse-feed, semibatch, semi-continuous, continuous). After a careful literature examination, two-step heterotrophic or mixotrophic cultivation strategies are suggested to surpass the lutein productivity achieved in single-step photosynthetic cultures. Furthermore, this review highlights the urgent need to develop technical feasibility studies at a pilot scale for these cultivation strategies, which will strengthen the necessary techno-economic analyses to drive their commercial production.