# Challenges and Potential in Increasing Lutein Content in Microalgae
## 1 Introduction  
Lutein ((3R, 3\({}^{\prime}\)R, 6\({}^{\prime}\)R)-\(\beta\), \(\varepsilon\)-carotene-3, 3\({}^{\prime}\)-diol) is a C40 hydroxyl-carotenoid with a chemical structure that has an unsaturated polyene chain as the skeleton, one \(\varepsilon\)-ring and one \(\beta\)-ring on each side of the skeleton, with a hydroxyl-group on the 3\({}^{\prime}\) site of each ring. Lutein is primarily synthesized by plants and algae with two forms. In the first configuration, lutein is present as a \"structural form\", and its function is primarily involved in light-harvesting and nonphotochemical quenching [1, 2]. In the second form, with one or two fatty acids bound to the hydroxyl-groups, lutein is converted into \"oil form\" that is accumulated in lipid vessels of many flowers and fruits [3]. Lutein has demonstrated use as an antioxidant, a food coloring agent and a nutraceutical, and is thus widely used in cosmetics, food additives and drugs [4, 5]. The conjugated double bonds of lutein provide substantial antioxidant property. Because the human body cannot synthesize lutein and other carotenoids, dietary intake is vital to human health. Lutein and its isomer zeaxanthin provide unique health benefits to the human macular region. These are the only two carotenoids that are greatly enriched in the human retinal macula region to improve visual function, filter blue light and prevent oxidative damage [6]. In fact, a six milligram of daily intake of lutein can significantly lower the risk of age-related macular degeneration (AMD) [7, 8]. Studies also suggest that lutein may reduce the risk of some cancers and prevent heart disease and stroke [9, 10, 11, 12]. These beneficial effects of lutein on human health have prompted increased demand for lutein and resulted in a significant global lutein market. Algal-based lutein production provides a promising alternative to that extracted from marigold, although currently the commercial supply of lutein mainly depends on farming and extracting marigold petals in China, India and Mexico [4, 13, 14]. Compared withmargigold, microalgae have several unique characteristics. Microalgae grow much faster than marigold, leading to higher lutein annual productivity. They can be cultured in large-scale fermenters, photobioreactors or even open ponds. Therefore, microalgae-based lutein production is an industrially scalable process. It is also less susceptible to seasonal, climatic and land limitations than marigold-based lutein production [4; 13; 15]. In the past two decades, several microalgae species such as _Chlorella_ spp., _Scenedesmus_ spp., _Muriellopsis_ spp., and _Dunaliella_ spp. have been investigated for lutein production [16; 17; 18; 19]. Considering the high cost of cell harvesting, cell disruption and pigment extraction in microalgae-based lutein production, the studies suggest that lutein content need be greater than 10 mg/g to be commercially feasible [13]. However, algal lutein content averages around 5 mg/g of dry cell weight (DCW). Therefore, microalgae-based lutein production has not been commercialized yet, due to low lutein content in microalgal cells. Extensive studies have explored new algal species with naturally high lutein content, and have enhanced lutein content with different cultivation methods in the recent years (Table 1). [PERSON] et al. isolated a lutein-rich microalgae species, _Chlorella sorokiniana_ FZU60 [20]. After optimizing sodium acetate and nitrate concentration in the growth medium, maximum lutein content, lutein productivity and biomass productivity reached 9.65 mg/g, 4.86 mg/L/d, and 503.55 mg/L/d, separately. Pilot-scale cultivation of _C. sorokiniana_ FZU60 in a 50 L column photobioreactor was conducted and optimized. Optimum lutein content, lutein yield and lutein productivity were achieved at 9.51 mg/g, 33.55 mg/L, and 4.67 mg/L/d, separately, under a novel, two-stage cultivation mode [21]. [PERSON] et al. optimized and evaluated the lutein production of microalgae _Parachlorella_ sp. JD-076 under different types of photobioreactors.