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Pigment and qE protein accumulation in CC-125 and Mut-5 cultured in three light conditions. Pigment contents and qE protein accumulation in C. reinhardtii strains CC-125 (blue) and Mut-5 (red) acclimated to low light (LL; 70 µmol photons m² s⁻¹), medium light (ML; 150 µmol photons m² s⁻¹), and high light (HL; 400 µmol photons m² s⁻¹). Total chlorophyll (Chl) content in pg per cell A, total carotenoid (Car) content in pg per cell B, Chl a/Chl b ratios C, and Chl/Car ratios D are displayed. Data are represented as the mean of 3 independent replicates with error bars depicting standard deviation from the mean. For each parameter, significant differences between each strain and light condition were calculated by two-way ANOVA with a multiple comparisons test (compare cell means regardless of rows and columns) and post hoc Bonferroni correction. Means marked with the same letter are not significantly different (p-value > 0.05). E Immunoblots showing LHCSR1, LHCSR3, and PSBS expression in CC-125 (WT) and Mut-5 (M5) under LL, ML, and HL. Antibodies detecting α-ATPase β-subunit were included as a control
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Microalgae are emerging hosts for the sustainable production of lutein, a high-value carotenoid; however, to be commercially competitive with existing systems, their capacity for lutein sequestration must be augmented. Previous attempts to boost microalgal lutein production have focussed on upregulating carotenoid biosynthetic enzymes, i...
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Citations
... The biological production of astaxanthin, however, is restrained by the slow growth of its native producer, the freshwater Chlorophyte Haematococcus lacustris (previously named Haematococcus pluvialis) [176]. Accordingly, the establishment of optimal cultivation strategies of H. lacustris and the domestication of high-yielding strains are key to accruing astaxanthin accumulation [177][178][179][180]. ...
From sea shores to the abysses of the deep ocean, marine ecosystems have provided humanity with valuable medicinal resources. The use of marine organisms is discussed in ancient pharmacopoeias of different times and geographic regions and is still deeply rooted in traditional medicine. Thanks to present-day, large-scale bioprospecting and rigorous screening for bioactive metabolites, the ocean is coming back as an untapped resource of natural compounds with therapeutic potential. This renewed interest in marine drugs is propelled by a burgeoning research field investigating the molecular mechanisms by which newly identified compounds intervene in the pathophysiology of human diseases. Of great clinical relevance are molecules endowed with anti-inflammatory and immunomodulatory properties with emerging applications in the management of chronic inflammatory disorders, autoimmune diseases, and cancer. Here, we review the historical development of marine pharmacology in the Eastern and Western worlds and describe the status of marine drug discovery. Finally, we discuss the importance of conducting sustainable exploitation of marine resources through biotechnology.
... In C. reinhardtii, α-carotene is hydroxylated by the activity of P450 ε/ß-ring hydroxylases (CYP97A and CYP97C) [9] at both C3 positions for the synthesis of lutein, a common, yellow-red colored xanthophyll found in all green plants and their progenitors. The native cellular abundance in C. reinhardtii varies depending on the present light intensity [10], is reported to range between 1.77 and 4.13 mg/g [11][12][13], and was engineered to 8.9 mg/g [12] by the overexpression of Xanthophyllomyces dendrorhous phytoene-β-carotene synthase (crtYB). An alternative strategy, by the overexpression of C. reinhardtii LCYE, resulted in a 2.6-fold increased lutein production (to 0.48 mg/L) [14]. ...
Carotenoids are valuable pigments naturally occurring in all photosynthetic plants and microalgae as well as in selected fungi, bacteria, and archaea. Green microalgae developed a complex carotenoid profile suitable for efficient light harvesting and light protection and harbor great capacity for carotenoid production through the substantial power of the endogenous 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway. Previous works established successful genome editing and induced significant changes in the cellular carotenoid content in Chlamydomonas reinhardtii. This study employs a tailored carotenoid pathway for engineered bioproduction of the valuable ketocarotenoid astaxanthin. Functional knockout of lycopene ε-cyclase (LCYE) and non-homologous end joining (NHEJ)-based integration of donor DNA at the target site inhibit the accumulation of α-carotene and consequently lutein and loroxanthin, abundant carotenoids in C. reinhardtii without changes in cellular fitness. PCR-based screening indicated that 4 of 96 regenerated candidate lines carried (partial) integrations of donor DNA and increased ß-carotene as well as derived carotenoid contents. Iterative overexpression of CrBKT, PacrtB, and CrCHYB resulted in a 2.3-fold increase in astaxanthin accumulation in mutant ∆LCYE#3 (1.8 mg/L) compared to the parental strain UVM4, which demonstrates the potential of genome editing for the design of a green cell factory for astaxanthin bioproduction.
... Lutein binds to proteins associated with the light-harvesting complex (LHC), part of photosystem II. The accumulation of the pigment is limited by the amount of LHC present in the chloroplast, linking increased lutein production in microalgae to expanded storage of this pigment [29,30]. Figure 3 illustrates the arrangement of xanthophylls in the microalgal cell. ...
... Table 1 presents the microalgae with the highest lutein content in the biomass (mg g −1 ) and those with the highest lutein productivity (mg L −1 d −1 ). Microalgae from the genus Chlamydomonas are commonly used in genetic manipulation [29,37] to improve lutein content, while Chlorella is the most studied so far for laboratory and industrial scales [38]. ...
Lutein, a yellow xanthophyll carotenoid, is increasingly recognized for its nutraceutical benefits, particularly in protecting the retina’s macula from age-related degeneration. Microalgae are a promising source of lutein, which can be a primary product or a coproduct in biorefineries. Certain microalgae exhibit lutein levels (up to 1.7%) surpassing those of common dietary sources like kale, spinach, and egg yolk (approximately 0.7–0.9%). Predominantly associated with photosystem II’s light-harvesting complex, lutein is crucial in photosynthesis and cellular defense. However, being quantitatively minor among cellular constituents, lutein necessitates specialized processing for efficient extraction. Although ubiquitous in microalgae, it is not as easily inducible as β-carotene and astaxanthin in Dunaliella salina and Haematococcus pluvialis, respectively. Currently, microalgal lutein production predominantly occurs at the bench scale, presenting challenges in scaling up. Factors like culture medium significantly influence biomass and lutein yields in industrial production, while downstream processing requires cost-effective, food-grade solvent extraction techniques. This review delves into contemporary methods and innovative progress in microalgal lutein production, emphasizing industrial-scale processes from biomass cultivation to final product formulation. A conceptual industrial process proposed in this review shows that two 10 m3 photobioreactors could produce 108 kg dry mass for Chlorella minutissima, which can be processed into approximately 616 g of lutein extract, or over 6000 capsules of finished nutraceutical daily. Despite lutein production via microalgae being in nascent stages at large scales, existing research provides a solid foundation for well-informed scale-up endeavors.
Rheumatoid arthritis (RA) is an invalidating chronic autoimmune disorder characterized by joint inflammation and progressive bone damage. Dietary intervention is an important component in the treatment of RA to mitigate oxidative stress, a major pathogenic driver of the disease. Alongside traditional sources of antioxidants, microalgae—a diverse group of photosynthetic prokaryotes and eukaryotes—are emerging as anti-inflammatory and immunomodulatory food supplements. Several species accumulate therapeutic metabolites—mainly lipids and pigments—which interfere in the pro-inflammatory pathways involved in RA and other chronic inflammatory conditions. The advancement of the clinical uses of microalgae requires the continuous exploration of phytoplankton biodiversity and chemodiversity, followed by the domestication of wild strains into reliable producers of said metabolites. In addition, the tractability of microalgal genomes offers unprecedented possibilities to establish photosynthetic microbes as light-driven biofactories of heterologous immunotherapeutics. Here, we review the evidence-based anti-inflammatory mechanisms of microalgal metabolites and provide a detailed coverage of the genetic engineering strategies to enhance the yields of endogenous compounds and to develop innovative bioproducts.
