Microbial chassis as the platform for production of dihydroxy xanthophyll-based carotenoids: an overview of recent advances in biomanufacturing.

Physiological and environmental cues prompt microbes to synthesize diverse carotenoids, including dihydroxy xanthophylls, facilitating their adaptation and survival. Lutein and its isomeric counterpart, zeaxanthin, are notable dihydroxy xanthophylls with bioactive properties such as antioxidative, anti-inflammatory, anticancer, and neuroprotective effects, particularly beneficial for human ocular health. However, global natural resources for co-producing lutein and zeaxanthin are scarce, with zeaxanthin lacking commercial sources, unlike lutein sourced from marigold plants and microalgae. Traditionally, dihydroxy xanthophyll production primarily relies on petrochemical synthetic routes, with limited biological sourcing reported. Nonetheless, microbiological synthesis presents promising avenues as a commercial source, albeit challenged by low dihydroxy xanthophyll yield at high cell density. Strategies involving optimization of physical and chemical parameters are essential to achieve high-quality dihydroxy xanthophyll products. This overview briefly discusses dihydroxy xanthophyll biosynthesis and highlights recent advancements, discoveries, and industrial benefits of lutein and zeaxanthin production from microorganisms as alternative biofactories.

Astaxanthin induces plant tolerance against cadmium by reducing cadmium uptake and enhancing carotenoid metabolism for antioxidant defense in wheat (Triticum aestivum L.).

Soil cadmium (Cd) contamination poses a significant threat to global food security and the environment. Astaxanthin (AX), a potent biological antioxidant belonging to the carotenoid group, has been demonstrated to confer tolerance against diverse abiotic stresses in plants. This study investigated the potential of AX in mitigating Cd-induced damage in wheat seedlings. Morpho-physiological, ultrastructural, and biochemical analyses were conducted to evaluate the impact of AX on Cd-exposed wheat seedlings. Illumina-based gene expression profiling was employed to uncover the molecular mechanisms underlying the protective effects of AX. The addition of 100 µM AX alleviated Cd toxicity by enhancing various parameters: growth, photosynthesis, carotenoid content, and total antioxidant capacity (T-AOC), while reducing Cd accumulation, malondialdehyde (MDA), and hydrogen peroxide (H2O2) levels. RNA sequencing analysis revealed differentially expressed genes associated with Cd uptake and carotenoid metabolism, such as zinc/iron permease (ZIP), heavy metal-associated protein (HMA), 3-beta hydroxysteroid dehydrogenase/isomerase (3-beta-HSD), and thiolase. These findings suggest that AX enhances Cd tolerance in wheat seedlings by promoting the expression of detoxification and photosynthesis-related genes. This research offers valuable insights into the potential use of AX to address Cd contamination in agricultural systems, highlighting the significance of antioxidant supplementation in plant stress management.

Mediator subunit MED8 interacts with heat shock transcription factor HSF3 to promote fucoxanthin synthesis in the diatom Phaeodactylum tricornutum.

Fucoxanthin, a natural carotenoid that has substantial pharmaceutical value due to its anticancer, antioxidant, antiobesity, and antidiabetic properties, is biosynthesized from glyceraldehyde-3-phosphate (G3P) via a series of enzymatic reactions. However, our understanding of the transcriptional mechanisms involved in fucoxanthin biosynthesis remains limited. Using reverse genetics, the med8 mutant was identified based on its phenotype of reduced fucoxanthin content, and the biological functions of MED8 in fucoxanthin synthesis were characterized using approaches such as gene expression, protein subcellular localization, protein-protein interaction and chromatin immunoprecipitation assay. Gene-editing mutants of MED8 exhibited decreased fucoxanthin content as well as reduced expression levels of six key genes involved in fucoxanthin synthesis, namely DXS, PSY1, ZDS-like, CRTISO5, ZEP1, and ZEP3, when compared to the wild-type (WT) strain. Furthermore, we showed that MED8 interacts with HSF3, and genetic analysis revealed their shared involvement in the genetic pathway governing fucoxanthin synthesis. Additionally, HSF3 was required for MED8 association with the promoters of the six fucoxanthin synthesis genes. In conclusion, MED8 and HSF3 are involved in fucoxanthin synthesis by modulating the expression of the fucoxanthin synthesis genes. Our results increase the understanding of the molecular regulation mechanisms underlying fucoxanthin synthesis in the diatom P. tricornutum.

The impact of long-term acclimation to different growth light intensities on the regulation of zeaxanthin epoxidase in different plant species.

Proper short- and long-term acclimation to different growth light intensities is essential for the survival and competitiveness of plants in the field. High light exposure is known to induce the down-regulation and photoinhibition of photosystem II (PSII) activity to reduce photo-oxidative stress. The xanthophyll zeaxanthin (Zx) serves central photoprotective functions in these processes. We have shown in recent work with different plant species (Arabidopsis, tobacco, spinach and pea) that photoinhibition of PSII and degradation of the PSII reaction center protein D1 is accompanied by the inactivation and degradation of zeaxanthin epoxidase (ZEP), which catalyzes the reconversion of Zx to violaxanthin. Different high light sensitivity of the above-mentioned species correlated with differential down-regulation of both PSII and ZEP activity. Applying light and electron microscopy, chlorophyll fluorescence, and protein and pigment analyses, we investigated the acclimation properties of these species to different growth light intensities with respect to the ability to adjust their photoprotective strategies. We show that the species differ in phenotypic plasticity in response to short- and long-term high light conditions at different morphological and physiological levels. However, the close co-regulation of PSII and ZEP activity remains a common feature in all species and under all conditions. This work supports species-specific acclimation strategies and properties in response to high light stress and underlines the central role of the xanthophyll Zx in photoprotection.

A novel drying film culture method applying a natural phenomenon: Increased carotenoid production by Haematococcus sp.

Low productivity and high cost remain major bottlenecks for the large-scale production of Haematococcus sp. This study explored biomass production and carotenoid accumulation in Haematococcus sp. (KCTC 12348BP) using drying film culture. The broth-cultured strain (3.2 × 106 cells/mL, 0.83 ± 0.02 mg/mL for a 21 d culture) was cultured under various conditions (different inoculum volumes and mist feeding intervals) in waterless agar plates at 28 ± 0.5 °C, under fluorescent light (12 h light-dark cycle) for 1 month. The maximum biomass obtained was 17.60 ± 0.72 g/m2, while the maximum astaxanthin concentration was 8.23 ± 1.13 mg/g in the culture using 1 mL inoculum and 3 d feeding interval. Drought stress in drying film culture effectively induced the accumulation of carotenoids from ß-carotene, facilitating the production of canthaxanthin via the astaxanthin biosynthesis pathway. This cost-effective culture system can increase the biomass and carotenoid pigment production in Haematococcus sp.

The Amount of Zeaxanthin Epoxidase But Not the Amount of Violaxanthin De-Epoxidase Is a Critical Determinant of Zeaxanthin Accumulation in Arabidopsis thaliana and Nicotiana tabacum.

The generation of violaxanthin (Vx) de-epoxidase (VDE), photosystem II subunit S (PsbS) and zeaxanthin (Zx) epoxidase (ZEP) (VPZ) lines, which simultaneously overexpress VDE, PsbS and ZEP, has been successfully used to accelerate the kinetics of the induction and relaxation of non-photochemical quenching (NPQ). Here, we studied the impact of the overexpression of VDE and ZEP on the conversion of the xanthophyll cycle pigments in VPZ lines of Arabidopsis thaliana and Nicotiana tabacum. The protein amount of both VDE and ZEP was determined to be increased to about 3- to 5-fold levels of wild-type (WT) plants for both species. Compared to WT plants, the conversion of Vx to Zx, and hence VDE activity, was only marginally accelerated in VPZ lines, whereas the conversion of Zx to Vx, and thus ZEP activity, was strongly increased in VPZ lines. This indicates that the amount of ZEP but not the amount of VDE is a critical determinant of the equilibrium of the de-epoxidation state of xanthophyll cycle pigments under saturating light conditions. Comparing the two steps of epoxidation, particularly the second step (antheraxanthin to Vx) was found to be accelerated in VPZ lines, implying that the intermediate Ax is released into the membrane during epoxidation by ZEP.

Lutein and zeaxanthin - radio- and chemoprotective properties. Mechanism and possible use.

Lutein and zeaxanthin are naturally occurring xanthophylls, mainly present in green, leafy vegetables and egg's yolk. Their presence is connected with blue spectrum light absorbance, including UV. This property, and fact, that these xanthophylls are accumulated by human eye's macula, leads to eye's protective functions of them including protection from age-related macular degeneration (AMD). Also, antioxidative features of lutein and zeaxanthin are boosting overall health of human body. Numerous studies proves anti-inflammatory and protective attributes of these compounds, based on many, different mechanisms. One of them is regulating redox potential in cells, and impact on expression of linked genes. In preventing of eye diseases, an important gene that is regulated by lutein and zeaxanthin is the Nrf2 gene, whose increased activity leads to optimizing the cellular response to reactive oxygen species (ROS) and preventing related diseases. Other research confirms antiproliferative properties of mentioned compounds in case of certain human cancer cell lines. There are e.g.: HepG2 (hepatitis cancer), MCF-7 (breast cancer), which treated in vitro with lutein solution showed reduction of cell growth. Lutein alone, during in vivo studies conducted on mice, exhibited also radioprotective properties, positively affecting the vitality of animals. Lutein provides also increasing of tolerance to UV radiation, reducing inflammatory processes in the skin and preventing oncogenesis. Low intake of lutein and zeaxanthin, associated with "western diet", rich in simple carbohydrates and processed food, common in developed countries, including Poland, is linked with diabetes and obesity incidence. Assuming, lutein and zeaxanthin significantly affect the well-being of the human body, and their appropriate amount in diet can help reduce risk of many diseases. For supplementation, the optimized dosage of these xanthophylls includes doses of 10 mg for lutein and 2 mg for zeaxanthin, and it is recommended to consume along with fats or meals rich in fats.

The Role of Fucoxanthin in Non-Alcoholic Fatty Liver Disease.

Chronic liver disease (CLD) has emerged as a leading cause of human deaths. It caused 1.32 million deaths in 2017, which affected men more than women by a two-to-one ratio. There are various causes of CLD, including obesity, excessive alcohol consumption, and viral infection. Among them, non-alcoholic fatty liver disease (NAFLD), one of obesity-induced liver diseases, is the major cause, representing the cause of more than 50% of cases. Fucoxanthin, a carotenoid mainly found in brown seaweed, exhibits various biological activities against NAFLD. Its role in NAFLD appears in several mechanisms, such as inducing thermogenesis in mitochondrial homeostasis, altering lipid metabolism, and promoting anti-inflammatory and anti-oxidant activities. The corresponding altered signaling pathways are the ß3-adorenarine receptor (ß3Ad), proliferator-activated receptor gamma coactivator (PGC-1), adenosine monophosphate-activated protein kinase (AMPK), peroxisome proliferator-activated receptor (PPAR), sterol regulatory element binding protein (SREBP), nuclear factor kappa B (NF-κB), mitogen-activated protein kinase (MAPK), protein kinase B (AKT), SMAD2/3, and P13K/Akt pathways. Fucoxanthin also exhibits anti-fibrogenic activity that prevents non-alcoholic steatohepatitis (NASH) development.

A Review of the Effects of Fucoxanthin on NAFLD.

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent form of chronic liver disease. Fucoxanthin, a red-orange marine carotenoid, is found in natural marine seaweeds with high antioxidant activity and several other remarkable biological features. The aim of this review is to gather evidence of the positive benefits of fucoxanthin on NAFLD. Fucoxanthin provides an extensive list of physiological and biological properties, such as hepatoprotective, anti-obesity, anti-tumor, and anti-diabetes properties, in addition to antioxidant and anti-inflammatory properties. This review focuses on published research on the preventative effects of fucoxanthin on NAFLD from the perspective of human clinical trials, animal experiments in vivo, and in vitro cell investigations. Using a variety of experimental designs, including treatment dosage, experiment model, and experimental periods, the positive effects of fucoxanthin were demonstrated. Fucoxanthin's biological activities were outlined, with an emphasis on its therapeutic efficacy in NAFLD. Fucoxanthin showed beneficial effects in modulating lipid metabolism, lipogenesis, fatty acid oxidation, adipogenesis, and oxidative stress on NAFLD. A deeper comprehension of NAFLD pathogenesis is essential for the development of novel and effective therapeutic strategies.

Carotenoid Pathway Engineering in Tobacco Chloroplast Using a Synthetic Operon.

The carotenoid pathway in plants has been altered through metabolic engineering to enhance their nutritional value and generate keto-carotenoids, which are widely sought after in the food, feed, and human health industries. In this study, the aim was to produce keto-carotenoids by manipulating the native carotenoid pathway in tobacco plants through chloroplast engineering. Transplastomic tobacco plants were generated that express a synthetic multigene operon composed of three heterologous genes, with Intercistronic Expression Elements (IEEs) for effective mRNA splicing. The metabolic changes observed in the transplastomic plants showed a significant shift towards the xanthophyll cycle, with only a minor production of keto-lutein. The use of a ketolase gene in combination with the lycopene cyclase and hydroxylase genes was a novel approach and demonstrated a successful redirection of the carotenoid pathway towards the xanthophyll cycle and the production of keto-lutein. This study presents a scalable molecular genetic platform for the development of novel keto-carotenoids in tobacco using the Design-Build-Test-Learn (DBTL) approach. This study corroborates chloroplast metabolic engineering using a synthetic biology approach for producing novel metabolites belonging to carotenoid class in industrially important tobacco plant. The synthetic multigene construct resulted in producing a novel metabolite, keto-lutein with high accumulation of xanthophyll metabolites. This figure was drawn using BioRender ( https://www.biorender.com ).

Metabolite analysis of soybean oil on promoting astaxanthin production of Phaffia rhodozyma.

BACKGROUND: Astaxanthin is a carotenoid with strong antioxidant property. In addition, it has anti-cancer, anti-tumor, anti-inflammatory and many other functions. The micro-organisms that mainly produce astaxanthin are Haematococcus pluvialis and Phaffia rhodozyma. Compared with H. pluvialis, P. rhodozyma has shorter fermentation cycle and easier to control culture conditions, but the yield of astaxanthin in P. rhodozyma is low. This article studied how to improve the astaxanthin production of P. rhodozyma. RESULTS: The results showed that when 10 mL L-1 soybean oil was added to the culture medium, astaxanthin production increased significantly, reaching 7.35 mg L-1 , which was 1.4 times that of the control group, and lycopene and ß-carotene contents also increased significantly. Through targeted metabolite analysis, the fatty acids in P. rhodozyma significantly increased under the soybean oil stimulation, especially the fatty acids closely related to the formation of astaxanthin esters, included palmitic acid (C16:0), stearic acid (C18:0), oleic acid (C18:1n9), linoleic acid (C18:2n6), α-linolenic acid (C18:3n3) and γ-linolenic acid (C18:3n6), thereby increasing the astaxanthin esters content. CONCLUSION: It showed that the addition of soybean oil can promote the accumulation of astaxanthin by promoting the increase of astaxanthin ester content. © 2022 Society of Chemical Industry.

Anti-Oxidant and Anti-Inflammatory Effects of Astaxanthin on Gastrointestinal Diseases.

A moderate amount of reactive oxygen species (ROS) is produced under normal conditions, where they play an important role in cell signaling and are involved in many aspects of the immune response to pathogens. On the other hand, the excessive production of ROS destructs macromolecules, cell membranes, and DNA, and activates pro-inflammatory signaling pathways, which may lead to various pathologic conditions. Gastrointestinal (GI) mucosa is constantly exposed to ROS due to the presence of bacteria and other infectious pathogens in food, as well as alcohol consumption, smoking, and the use of non-steroidal anti-inflammatory drugs (NSAID). Prolonged excessive oxidative stress and inflammation are two major risk factors for GI disorders such as ulcers and cancers. Bioactive food compounds with potent anti-oxidant and anti-inflammatory activity have been tested in experimental GI disease models to evaluate their therapeutic potential. Astaxanthin (AST) is a fat-soluble xanthophyll carotenoid that is naturally present in algae, yeast, salmon, shrimp, and krill. It has been shown that AST exhibits protective effects against GI diseases via multiple mechanisms. Residing at the surface and inside of cell membranes, AST directly neutralizes ROS and lipid peroxyl radicals, enhances the activity of anti-oxidant enzymes, and suppresses pro-inflammatory transcription factors and cytokines. In addition, AST has been shown to inhibit cancer cell growth and metastasis via modulating cell proliferation-related pathways, apoptosis, and autophagy. Considering the potential benefits of AST in GI diseases, this review paper aims to summarize recent advances in AST research, focusing on its anti-oxidant and anti-inflammatory effects against gastric and intestinal ulcers and cancers.

Astaxanthin ameliorates serum level and spinal expression of macrophage migration inhibitory factor following spinal cord injury.

Astaxanthin (AST) is a lipid-soluble carotenoid with antioxidant and anti-inflammatory properties. Previous reports demonstrated the promising effects of AST on spinal cord injury (SCI)-induced inflammation and sensory-motor dysfunction. Macrophage migration inhibitory factor (MIF), as a cytokine, plays a critical role in the inflammatory phase of SCI. The aim of this study was to evaluate the effects of AST on post-SCI levels of MIF in serum and spinal cord. The possible correlation between MIF and mechanical pain threshold was also assessed. Adult male rats were subjected to a severe compression spinal injury and 30 min later were treated with AST (Intrathecal, 2 nmol) or vehicle. Neuropathic pain was assessed by von Frey filaments before the surgery, and then on days 7, 14, 21, and 28 post-SCI. Western blot and ELISA were used to measure the serum level and spinal expression of MIF following SCI in the same time points. AST treatment significantly attenuated the SCI-induced dysregulations in the serum levels and tissue expression of MIF. A negative correlation was observed between mechanical pain threshold and serum MIF level (r = -0.5463, P < 0.001), as well as mechanical pain threshold and spinal level of MIF (r = -0.9562; P < 0.001). AST ameliorates SCI-induced sensory dysfunction, probably through inhibiting MIF-regulated inflammatory pathways.

Astaxanthin Inhibits Matrix Metalloproteinase Expression by Suppressing PI3K/AKT/mTOR Activation in Helicobacter pylori-Infected Gastric Epithelial Cells.

Helicobacter pylori (H. pylori) increases production of reactive oxygen species (ROS) and activates signaling pathways associated with gastric cell invasion, which are mediated by matrix metalloproteinases (MMPs). We previously demonstrated that H. pylori activated mitogen-activated protein kinase (MAPK) and increased expression of MMP-10 in gastric epithelial cells. MMPs degrade the extracellular matrix, enhancing tumor invasion and cancer progression. The signaling pathway of phosphatidylinositol 3-kinase (PI3K)/serine/threonine protein kinase B (AKT)/mammalian target of rapamycin (mTOR) is associated with MMP expression. ROS activates PIK3/AKT/mTOR signaling in cancer. Astaxanthin, a xanthophyll carotenoid, shows antioxidant activity by reducing ROS levels in gastric epithelial cells infected with H. pylori. This study aimed to determine whether astaxanthin inhibits MMP expression, cell invasion, and migration by reducing the PI3K/AKT/mTOR signaling in H. pylori-infected gastric epithelial AGS cells. H. pylori induced PIK3/AKT/mTOR and NF-κB activation, decreased IκBα, and induced MMP (MMP-7 and -10) expression, the invasive phenotype, and migration in AGS cells. Astaxanthin suppressed these H. pylori-induced alterations in AGS cells. Specific inhibitors of PI3K, AKT, and mTOR reversed the H. pylori-stimulated NF-κB activation and decreased IκBα levels in the cells. In conclusion, astaxanthin suppressed MMP expression, cell invasion, and migration via inhibition of PI3K/AKT/mTOR/NF-κB signaling in H. pylori-stimulated gastric epithelial AGS cells.

Photoacclimation impacts the molecular features of photosystem supercomplexes in the centric diatom Thalassiosira pseudonana.

In diatoms, light-harvesting processes take place in a specific group of proteins, called fucoxanthin chlorophyll a/c proteins (FCP). This group includes many members and represents the major characteristic of the diatom photosynthetic apparatus, with specific pigments bound (chlorophyll c, fucoxanthin, diadino- and diatoxanthin besides chlorophyll a). In thylakoids, FCP and photosystems (PS) form multimeric supercomplexes. In this study, we compared the biochemical properties of PS supercomplexes isolated from Thalassiosira pseudonana cells grown under low light or high light conditions, respectively. High light acclimation changed the molecular features of the PS and their ratio in thylakoids. In PSII, no obvious changes in polypeptide composition were observed, whereas for PSI changes in one specific group of FCP proteins were detected. As reported before, the amount of xanthophyll cycle pigments and their de-epoxidation ratio was increased in PSI under HL. In PSII, however, no additional xanthophyll cycle pigments occurred, but the de-epoxidation ratio was increased as well. This comparison suggests how mechanisms of photoprotection might take place within and in the proximity of the PS, which gives new insights into the capacity of diatoms to adapt to different conditions and in different environments.

Antioxidant Activity and Carotenoid Content Responses of Three Haematococcus sp. (Chlorophyta) Strains Exposed to Multiple Stressors.

There has been increasing demands worldwide for bioactive compounds of natural origins, especially for the nutraceutical and food-supplement sectors. In this context, microalgae are viewed as sustainable sources of molecules with an array of health benefits. For instance, astaxanthin is a xanthophyll pigment with powerful antioxidant capacity produced by microalgae such as the chlorophyte Haematococcus sp., which is regarded as the most suitable organism for the mass production of this pigment. In this study, three Haematococcus sp. strains were cultivated using a batch mode under favourable conditions to promote vegetative growth. Their environment was altered in a second phase using a higher and constant illumination regime combined with either exposure to blue LED light, an osmotic shock (with NaCl addition) or supplementation with a phytohormone (gibberellic acid, GA3), a plant extract (ginger), an herbicide (molinate) or an oxidant reagent (hydrogen peroxide). The effects of these stressors were evaluated in terms of antioxidant response and astaxanthin and ß-carotene accumulation. Overall, strain CCAP 34/7 returned the highest Trolox Equivalent Antioxidant Capacity (TEAC) response (14.1-49.1 µmoL Trolox eq. g- 1 of DW), while the highest antioxidant response with the Folin-Ciocalteu (FC) was obtained for strain RPFW01 (62.5-155 µmoL Trolox eq. g- 1 of DW). The highest ß-ß-carotene content was found in strain LAFW15 when supplemented with the ginger extract (4.8 mg. g- 1). Strain RPFW01 exposed to blue light returned the highest astaxanthin yield (2.8 mg. g- 1), 5-fold that of strain CCAP 34/7 on average. This study documents the importance of screening several strains when prospecting for species with potential to produce high-value metabolites. It highlights that strain-specific responses can ensue from exposure of cells to a variety of stressors, which is important for the adequate tailoring of a biorefinery pipeline.

Fucoxanthin Attenuates Free Fatty Acid-Induced Nonalcoholic Fatty Liver Disease by Regulating Lipid Metabolism/Oxidative Stress/Inflammation via the AMPK/Nrf2/TLR4 Signaling Pathway.

Fucoxanthin, a xanthophyll carotenoid abundant in brown algae, is reported to have several biological functions, such as antioxidant, anti-inflammatory, and anti-tumor activities, in mice. We investigated the effects and mechanisms of fucoxanthin in the mixture oleate/palmitate = 2/1(FFA)-induced nonalcoholic fatty liver disease (NAFLD) cell model in this study. The results showed that the content of superoxide dismutase in the FFA group was 9.8 ± 1.0 U/mgprot, while that in the fucoxanthin high-dose (H-Fx) group (2 µg/mL) increased to 22.9 ± 0.6 U/mgprot. The content of interleukin-1ß in the FFA group was 89.3 ± 3.6 ng/mL, while that in the H-Fx group was reduced to 53.8 ± 2.8 ng/mL. The above results indicate that fucoxanthin could alleviate the FFA-induced oxidative stress and inflammatory levels in the liver cells. Oil red-O staining revealed visible protrusions and a significant decrease in the number of lipid droplets in the cytoplasm of cells in the fucoxanthin group. These findings on the mechanisms of action suggest that fucoxanthin can repair FFA-induced NAFLD via the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway and nuclear factor erythroid-2-related factor 2-mediated (Nrf2) signaling pathway, as well as by downregulating the expression of the Toll-like receptor 4-mediated (TLR4) signaling pathway. Fucoxanthin exhibited alleviating effects in the FFA-induced NAFLD model and could be explored as a potential anti-NAFLD substance.

ß-Carotene-production methods, biosynthesis from Phaffia rhodozyma, factors affecting its production during fermentation, pharmacological properties: A review.

ß-Carotene is the most treasured provitamin A carotenoid molecule exhibiting antioxidant and coloring properties and significant applications in the food, pharmaceutical, and nutraceutical industries. ß-Carotene has many biological functions within the human body; however, it is not synthesized within the human body, so its requirements are fulfilled through food and pharmaceuticals. Its manufacturing via chemical synthesis or extraction from plants offers low yields with excessive manufacturing expenses, which attracted the researchers toward microbial production of ß-carotene. This alternative provides higher yield and low expenses and thus is more economical. Phaffia rhodozyma is a basidiomycetous yeast that is utilized to prevent cardiovascular diseases and cancer and to enhance immunity and antiaging in people. This paper reviews the methods of production of ß-carotene, biosynthesis of ß-carotene fromP. rhodozyma, factors affecting ß-carotene production during fermentation, and pharmacological properties of ß-carotene.

Enhancement of astaxanthin incorporation by pulsed high-intensity ultrasound in LPS-stimulated macrophages.

PURPOSE: Ultrasound (US) has been reported to improve the permeability of cell membranes to pharmaceuticals by causing cavitation. Astaxanthin (AX) potently terminates the induction of inflammation, but it has low oral bioavailability, which limits its incorporation in local cells and organs and its therapeutic potential. In this study, we aimed to investigate the contribution of US to AX incorporation to compensate for the limited incorporation of AX, and regulation of the pro-inflammatory factor interleukin-1ß (IL-1ß) by AX. METHODS: Murine bone marrow-derived macrophages were stimulated by lipopolysaccharide (LPS). After 2 h, cells were treated with 10 µM AX and/or pulsed high-intensity US irradiation. The cells were then incubated for another 3 h and harvested. AX incorporation in cells was measured by absorbance, and the expression of IL-1ß was measured by qPCR. All values are expressed as means ± standard error of the mean. RESULTS: The combination of AX and US significantly increased AX incorporation in cells compared to AX alone (p < 0.05). In addition, this combination further suppressed the expression of IL-1ß compared to AX alone (p < 0.05). CONCLUSION: Pulsed high-intensity US irradiation combined with AX treatment promoted AX incorporation in cells and enhanced the anti-inflammatory effect on macrophages.