•Astaxanthin and β-carotene have the highest demand in global carotenoid market.•Solvent extraction provides the highest productivity in carotenoid extraction.•Pretreatment methods have a significant ...impact on recovery percentage of carotenoid.•Bio refinery routes are cost effective and efficient to use in industrial scale.•Microalga based bio refineries have higher productivity than conventional methods.
Astaxanthin and β-carotene are important carotenoids used in numerous pharmaceutical and nutraceutical applications, owing to their vigorous antioxidant properties. The microalgal strains Haematococcus pluvialis and Dunaliella salina accumulate the highest quantities of astaxanthin and β-carotene (up to 7% and 13% dry weight respectively) and are therefore considered as sustainable feedstock for the commercial production of carotenoids. Thus, from an economical perspective, it becomes desirable to optimize recovery of carotenoids from microalgal cells. To this end, here, we have summarized the conventional and modern extraction techniques generally used for the recovery of astaxanthin from Haematococcus pluvialis and β-carotene from Dunaliella salina. Furthermore, we have also discussed the optimum process conditions employed for numerous extraction protocols including solvent extraction, ultrasonic-assisted extraction (UAE), microwave-assisted extraction (MAE) and supercritical fluid extraction (SFE). Overall, our study highlights the sustainability of integrated co-production of biofuels and carotenoids in a biorefinery framework.
Vitamin A deficiency is a major public health problem in developing countries. Some studies also implicate a suboptimal vitamin A intake in certain parts of the population of the industrialized ...world. Provitamin A carotenoids such as β-carotene are the major source for retinoids (vitamin A and its derivatives) in the human diet. However, it is still controversial how much β-carotene intake is required and safe. An important contributor to this uncertainty is the lack of knowledge about the biochemical and molecular basis of β-carotene metabolism. Recently, key players of provitamin A metabolism have been molecularly identified and biochemically characterized. Studies in knockout mouse models showed that intestinal β-carotene absorption and conversion to retinoids is under negative feedback regulation that adapts this process to the actual requirement of vitamin A of the body. These studies also showed that in peripheral tissues a conversion of β-carotene occurs and affects retinoid-dependent physiologic processes. Moreover, these analyses provided a possible explanation for the adverse health effects of carotenoids by showing that a pathologic accumulation of these compounds can induce oxidative stress in mitochondria and cell signaling pathways related to disease. Genetic polymorphisms in identified genes exist in humans and also alter carotenoid homeostasis. Here, the advanced knowledge of β-carotene metabolism is reviewed, which provides a molecular framework for understanding the role of this important micronutrient in health and disease.
Mammalian genomes encode two provitamin A-converting enzymes as follows: the β-carotene-15,15′-oxygenase (BCO1) and the β-carotene-9′,10′-oxygenase (BCO2). Symmetric cleavage by BCO1 yields retinoids ...(β-15′-apocarotenoids, C20), whereas eccentric cleavage by BCO2 produces long-chain (>C20) apocarotenoids. Here, we used genetic and biochemical approaches to clarify the contribution of these enzymes to provitamin A metabolism. We subjected wild type, Bco1−/−, Bco2−/−, and Bco1−/−Bco2−/− double knock-out mice to a controlled diet providing β-carotene as the sole source for apocarotenoid production. This study revealed that BCO1 is critical for retinoid homeostasis. Genetic disruption of BCO1 resulted in β-carotene accumulation and vitamin A deficiency accompanied by a BCO2-dependent production of minor amounts of β-apo-10′-carotenol (APO10ol). We found that APO10ol can be esterified and transported by the same proteins as vitamin A but with a lower affinity and slower reaction kinetics. In wild type mice, APO10ol was converted to retinoids by BCO1. We also show that a stepwise cleavage by BCO2 and BCO1 with APO10ol as an intermediate could provide a mechanism to tailor asymmetric carotenoids such as β-cryptoxanthin for vitamin A production. In conclusion, our study provides evidence that mammals employ both carotenoid oxygenases to synthesize retinoids from provitamin A carotenoids.
Background: Mammalian genomes encode two carotenoid oxygenases, but their contributions to vitamin A homeostasis remain undefined.
Results: Mammals employ symmetric and eccentric cleaving carotenoid oxygenases to convert different provitamin A carotenoids to vitamin A.
Conclusion: Both carotenoid oxygenases contribute to vitamin A production.
Significance: Carotenoids are the major source for vitamin A in the human diet.
Whereas conventional white cassava roots are devoid of provitamin A, biofortified yellow varieties are naturally rich in β-carotene, the primary provitamin A carotenoid.
We assessed the effect of ...consuming yellow cassava on serum retinol concentration in Kenyan schoolchildren with marginal vitamin A status.
We randomly allocated 342 children aged 5-13 y to receive daily, 6 d/wk, for 18.5 wk 1) white cassava and placebo supplement (control group), 2) provitamin A-rich cassava (mean content: 1460 μg β-carotene/d) and placebo supplement (yellow cassava group), and 3) white cassava and β-carotene supplement (1053 μg/d; β-carotene supplement group). The primary outcome was serum retinol concentration; prespecified secondary outcomes were hemoglobin concentration and serum concentrations of β-carotene, retinol-binding protein, and prealbumin. Groups were compared by using ANCOVA, adjusting for inflammation, baseline serum concentrations of retinol and β-carotene, and stratified design.
The baseline prevalence of serum retinol concentration <0.7 μmol/L and inflammation was 27% and 24%, respectively. For children in the control, yellow cassava, and β-carotene supplement groups, the mean daily intake of cassava was 378, 371, and 378 g, respectively, and the total daily supply of provitamin A and vitamin A from diet and supplements was equivalent to 22, 220, and 175 μg retinol, respectively. Both yellow cassava and β-carotene supplementation increased serum retinol concentration by 0.04 μmol/L (95% CI: 0.00, 0.07 μmol/L); correspondingly, serum β-carotene concentration increased by 524% (448%, 608%) and 166% (134%, 202%). We found no effect on hemoglobin concentration or serum concentrations of retinol-binding protein and prealbumin.
In our study population, consumption of yellow cassava led to modest gains in serum retinol concentration and a large increase in β-carotene concentration. It can be an efficacious, new approach to improve vitamin A status. This study was registered with clinicaltrials.gov as NCT01614483.
A significant progressive decline in beta-carotene (βC) levels in the brain is associated with cognitive impairment and a higher prevalence of Alzheimer's disease (AD). In this study, we investigated ...whether the administration of 9-cis beta-carotene (9CBC)-rich powder of the alga Dunaliella bardawil, the best-known source of βC in nature, inhibits the development of AD-like neuropathology and cognitive deficits. We demonstrated that in 3 AD mouse models, Tg2576, 5xFAD, and apoE4, 9CBC treatment improved long- and short-term memory, decreased neuroinflammation, and reduced the prevalence of β-amyloid plaques and tau hyperphosphorylation. These findings suggest that 9CBC has the potential to be an effective preventive and symptomatic AD therapy.
Plasma cholesterol is one of the strongest risk factors associated with the development of atherosclerotic cardiovascular disease (ASCVD) and myocardial infarction. Human studies suggest that ...elevated plasma β-carotene is associated with reductions in circulating cholesterol and the risk of myocardial infarction. The molecular mechanisms underlying these observations are unknown.
The objective of this study was to determine the impact of dietary β-carotene and the activity of β-carotene oxygenase 1 (BCO1), which is the enzyme responsible for the conversion of β-carotene to vitamin A, on circulating cholesterol concentration.
In our preclinical study, we compared the effects of a 10-d intervention with a diet containing 50 mg/kg of β-carotene on plasma cholesterol in 5-wk-old male and female C57 Black 6 wild-type and congenic BCO1-deficient mice. In our clinical study, we aimed to determine whether 5 common small nucleotide polymorphisms located in the BCO1 locus affected serum cholesterol concentrations in a population of young Mexican adults from the Universities of San Luis Potosí and Illinois: A Multidisciplinary Investigation on Genetics, Obesity, and Social-Environment (UP AMIGOS) cohort.
Upon β-carotene feeding,Bco1-/-mice accumulated >20-fold greater plasma β-carotene and had ~30 mg/dL increased circulating total cholesterol (P< 0.01) and non–HDL cholesterol (P< 0.01) than wild-type congenic mice. Our results in the UP AMIGOS cohort show that the rs6564851 allele ofBCO1, which has been linked to BCO1 enzymatic activity, was associated with a reduction in 10 mg/dL total cholesterol concentrations (P = 0.009) when adjusted for vitamin A and carotenoid intakes. non–HDL-cholesterol concentration was also reduced by 10 mg/dL when the data were adjusted for vitamin A and total carotenoid intakes (P = 0.002), or vitamin A and β-carotene intakes (P = 0.002).
Overall, our results in mice and young adults show that BCO1 activity impacts circulating cholesterol concentration, linking vitamin A formation with the risk of developing ASCVD.
Humans cannot synthesize vitamin A and thus must obtain it from their diet. β-Carotene 15,15′-oxygenase (BCO1) catalyzes the oxidative cleavage of provitamin A carotenoids at the central 15–15′ ...double bond to yield retinal (vitamin A). In this work, we quantitatively describe the substrate specificity of purified recombinant human BCO1 in terms of catalytic efficiency values (kcat/Km). The full-length open reading frame of human BCO1 was cloned into the pET-28b expression vector with a C-terminal polyhistidine tag, and the protein was expressed in the Escherichia coli strain BL21-Gold(DE3). The enzyme was purified using cobalt ion affinity chromatography. The purified enzyme preparation catalyzed the oxidative cleavage of β-carotene with a Vmax = 197.2 nmol retinal/mg BCO1 × h, Km = 17.2 μm and catalytic efficiency kcat/Km = 6098 m−1 min−1. The enzyme also catalyzed the oxidative cleavage of α-carotene, β-cryptoxanthin, and β-apo-8′-carotenal to yield retinal. The catalytic efficiency values of these substrates are lower than that of β-carotene. Surprisingly, BCO1 catalyzed the oxidative cleavage of lycopene to yield acycloretinal with a catalytic efficiency similar to that of β-carotene. The shorter β-apocarotenals (β-apo-10′-carotenal, β-apo-12′-carotenal, β-apo-14′-carotenal) do not show Michaelis-Menten behavior under the conditions tested. We did not detect any activity with lutein, zeaxanthin, and 9-cis-β-carotene. Our results show that BCO1 favors full-length provitamin A carotenoids as substrates, with the notable exception of lycopene. Lycopene has previously been reported to be unreactive with BCO1, and our findings warrant a fresh look at acycloretinal and its alcohol and acid forms as metabolites of lycopene in future studies.
Background: The human enzyme β-carotene 15,15′-oxygenase (BCO1) produces vitamin A from carotenoids in food.
Results: BCO1 catalyzes the oxidative cleavage of the 15–15′ double bond of major dietary provitamin A carotenoids, β-apocarotenals, and lycopene.
Conclusion: BCO1 reacts only with carotenoids and apocarotenoids that yield retinal or acycloretinal.
Significance: Elucidating the substrate specificity of BCO1 is crucial for understanding how humans metabolize carotenoids.
Vitamin A deficiency remains a nutritional concern in sub-Saharan Africa. Conventionally bred maize hybrids with high provitamin A carotenoid concentrations may have the potential to improve vitamin ...A status in maize-consuming populations.
We evaluated the efficacy of regular provitamin A carotenoid-biofortified "orange" maizemeal (∼15 μg β-carotene/g) consumption in improving vitamin A status and reducing vitamin A deficiency in children.
This was a cluster-randomized controlled trial in the rural farming district of Mkushi, Zambia. All 4- to 8-y-old children in an ∼400-km(2) area were identified and grouped by proximity into clusters of ∼15-25 children. We randomly assigned clusters to 1) orange maizemeal (n = 25), 2) white maizemeal (n = 25), or 3) a parallel, nonintervention group (n = 14). Children in intervention clusters (n = 1024) received 200 g maizemeal for 6 d/wk over 6 mo; the maizemeal was prepared according to standardized recipes and served in cluster-level kitchens. Staff recorded attendance and leftovers. We collected venous blood before and after the intervention to measure serum retinol, β-carotene, C-reactive protein, and α1-acid glycoprotein.
Intervention groups were comparable at baseline, and vitamin A status was better than anticipated (12.1% deficient on the basis of serum retinol <0.7 μmol/L). Although attendance at meals did not differ (85%), median daily maize intake was higher in white (154 g/d) than in orange (142 g/d) maizemeal clusters. At follow-up, mean serum β-carotene was 0.14 μmol/L (95% CI: 0.09, 0.20 μmol/L) higher in orange maizemeal clusters (P < 0.001), but mean serum retinol (1.00 ± 0.33 μmol/L overall) and deficiency prevalence (17.1% overall) did not differ between arms.
In this marginally nourished population, regular biofortified maizemeal consumption increased serum β-carotene concentrations but did not improve serum retinol. This trial was registered at clinicaltrials.gov as NCT01695148.
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