Microalgae-derived tocopherols: Biotechnological advances in production and its therapeutic potentials

Tocopherols are antioxidants that have the potential to prevent chronic diseases. Currently, most tocopherols are produced via chemical synthesis that are often impure, less active, and have side effects. Natural tocopherols are only synthesized by photoautotrophs, and microalgae can accumulate a considerable amount of tocopherols up to 4 mg/g DW, in which alpha-tocopherol comprising up to 97% (similar to 3.88 mg/g DW) which is remarkably higher than other phototrophs. Microalgal tocopherol production is still limited to laboratory scale due to low biomass productivity, high cultivation cost, and low tocopherol recovery. This review aims to explore advanced biotechnological strategies such as optimizing cultivation conditions i.e., temperature, light intensity, and photoperiod, implementing nutrient stress, genetic manipulation, and producing valuable coproducts along tocopherols to overcome these challenges. The review provides a comprehensive comparison of advanced extraction technologies, including Solvent extraction, Ultrasoundassisted extraction, Microwave-assisted extraction, Matrix solid-phase dispersion, Pressurized liquid extraction, Supercritical fluid extraction, and Cell milking, and evaluates their efficiency and eco-friendliness in microalgal tocopherol extraction. This review discusses the potential therapeutic uses of microalgae-derived tocopherols in various diseases like cancer, Alzheimer's disease, cardiovascular disease, hyperglycemia, obesity, and skin aging. It also provides an update on their current market scenario and prospects.