Improvement of Lutein Production in Auxenochlorella protothecoides Using Its Genome-Scale Metabolic Model and a System-Oriented Approach

Lutein is a valuable metabolite widely used in the food, pharmaceutical, cosmetic, and aquaculture industries. Marigold flowers are the most common source of commercial lutein, but cultivation area, weather conditions, and high manpower costs are among the disadvantages of lutein production from marigold flowers. Microalgae are an excellent alternative to plant sources of lutein as they do not have the limitations of plant extraction. Auxenochlorella protothecoides is a promising candidate for commercial production of lutein. In the present research, a genome-scale metabolic model was applied to introduce some strategies to improve lutein production in A. protothecoides. The effective reactions to improve lutein production were determined based on analysis of multiple optimal solutions. The enzymatic regulators of candidate reactions were identified using the BRENDA database. The effect of 13 activators was investigated experimentally. Our results showed that sodium citrate has the greatest effect on lutein production, so it was introduced as the most effective compound for increasing lutein production by A. protothecoides. Graphical abstract: [Figure not available: see fulltext.]