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.

The low and high doses administration of lutein improves memory and synaptic plasticity impairment through different mechanisms in a rat model of vascular dementia.

BACKGROUND AND AIM: Vascular dementia (VD) is a common type of dementia. This study aimed to evaluate the effects of low and high doses of lutein administration in bilateral-carotid vessel occlusion (2VO) rats. EXPERIMENTAL PROCEDURE: The rats were divided into the following groups: the control, sham-, vehicle (2VO+V) groups, and two groups after 2VO were treated with lutein 0.5 (2VO+LUT-o.5) and 5mg/kg (2VO+LUT-5). The passive-avoidance and Morris water maze were performed to examine fear and spatial memory. The field-potential recording was used to investigate the properties of basal synaptic transmission (BST), paired-pulse ratio (PPR), as an index for measurement of neurotransmitter release, and long-term potentiation (LTP). The hippocampus was removed to evaluate hippocampal cells, volume, and MDA level. RESULT: Treatment with low and high doses improves spatial memory and LTP impairment in VD rats, but only the high dose restores the fear memory, hippocampal cell loss, and volume and MDA level. Interestingly, low-dose, but not high-dose, increased PPR. However, BST recovered only in the high-dose treated group. CONCLUSIONS: Treatment with a low dose might affect neurotransmitter release probability, but a high dose affects postsynaptic processes. It seems likely that low and high doses improve memory and LTP through different mechanisms.

Lutein encapsulation into dual-layered starch/zein gels using 3D food printing: Improved storage stability and in vitro bioaccessibility.

The ability of 3D printing to encapsulate, protect, and enhance lutein bioaccessibility was investigated under various printing conditions. A spiral-cube-shaped geometry was used to investigate the effects of printing parameters, namely zein concentration (Z; 20, 40, and 60 %) and printing speed (PS; 4, 8, 14, and 20 mm/s). Coaxial extrusion 3D printing was used with lutein-loaded zein as the internal flow material, and corn starch paste as the external flow material. The viscosities of the inks, microstructural properties, storage stability, and bioaccessibility of encapsulated lutein were determined. The sample printed with a zein concentration of 40 % at a printing speed of 14 mm/s (Z-40/PS-14) exhibited the best shape integrity. When lutein was entrapped in starch/zein gels (Z-40/PS-14), only 39 % of lutein degraded after 21 days at 25 °C, whereas 78 % degraded at the same time when crude lutein was studied. Similar improvements were also observed after storing at 50 °C for 21 days. Furthermore, after simulated digestion, the bioaccessibility of encapsulated lutein (9.8 %) was substantially higher than that of crude lutein (1.5 %). As a result, the developed delivery system using 3D printing could be an effective strategy for enhancing the chemical stability and bioaccessibility of bioactive compounds (BCs).

Effect of Antioxidant Supplementation on Macular Pigment Optical Density and Visual Functions: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

Antioxidants are bioactive molecules that function to scavenge free radicals and balance oxidative stress. Although all antioxidants can act as reactive oxygen species scavengers, their efficacy on eye health may vary. Moreover, the comparative effectiveness and potential additive effect between groups of antioxidants, hitherto, have not been systematically studied. A systematic review and network meta-analysis were conducted to investigate the comparative or additive effect of dietary antioxidant supplements on eye health. Four databases (PubMed, Embase, CINAHL, and Cochrane) were searched, and relevant randomized controlled trials were identified. Out of 60 articles selected for systematic review, 38 were included in the network meta-analysis, categorized into 8 distinct antioxidant-supplemented groups and placebo. All groups significantly increased macular pigment optical density and contrast sensitivity at low spatial frequency, whereas only the antioxidant mixture + lutein (L) + fatty acid combination exhibited significant improvements in visual acuity (hazard ratio = -0.15; 95% confidence interval: -0.28, -0.02) and L + zeaxanthin combination for photostress recovery time (hazard ratio = -5.75; 95% confidence interval: -8.80, -1.70). Especially, the L + zeaxanthin + fatty acid combination was ranked best for macular pigment optical density (surface under the cumulative ranking: 99.3%) and second best for contrast sensitivity at low spatial frequency (67.7%). However, these findings should be interpreted with caution due to low quality of evidence, primarily influenced by indirectness and potential publication bias. Overall, antioxidant supplementation was estimated to improve eye health parameters, whereas different combinations of antioxidants may also have varying effects on improving visual health from multiple perspectives. This study was registered at PROSPERO as CRD42022369250.

Association between carotenoid intake and periodontitis in diabetic patients.

This study aimed to evaluate the association between dietary carotenoid intake and periodontitis in diabetic patients. Data on diabetic patients were collected from the National Health and Nutrition Examination Survey (NHANES) 2009-2014 for this cross-sectional study. Dietary intake of carotenoids was assessed through the first 24-hour dietary recall interview. Full-mouth periodontal examinations were conducted by trained dental examiners. Subgroup analysis was conducted in terms of age, gender, the number of missing teeth, cardiovascular disease, smoking, and anti-diabetic drugs. Totally 1914 diabetic patients were included, with 1281 (66.93%) in the periodontitis group. After adjusting for age, gender, race, education, smoking, dental implants, hepatitis, and the number of missing teeth, α-carotene intake ≥55.82 mcg was associated with lower odds of periodontitis than α-carotene intake <55.82 mcg [OR = 0.70, 95% CI: 0.53-0.91, P = 0.010]; lutein and zeaxanthin intake ≥795.95 mcg was associated with decreased odds of periodontitis than lutein and zeaxanthin intake <795.95 mcg (OR = 0.75, 95%CI: 0.57-0.98, P = 0.039). The association between carotenoid intake and periodontitis varied across different subpopulations. In diabetes, dietary intake of α-carotene and lutein and zeaxanthin was inversely associated with the odds of periodontitis, which may facilitate clinical periodontitis management.

Supplementation of rumen-protected lysine during the close-up period improves vaginal discharge clearance in Holstein dairy cows.

We aimed to evaluate the effects of rumen-protected lysine (RPL) supplementation during the close-up period on uterine involution and the resumption of ovarian function in dairy cows. Fifty-two multiparous Holstein cows were categorized based on parity and expected calving date and randomly assigned to the RPL or control (CON) groups. The RPL group received 80 g of RPL daily from day 21 before the expected calving date until parturition. Blood samples were obtained twice weekly from pre-supplementation to 6 weeks postpartum. The onset of luteal activity postpartum was determined via ultrasonography twice weekly for up to 6 weeks postpartum. Uterine involution was tracked at 3 and 5 weeks postpartum through the vaginal discharge score, percentage of polymorphonuclear cells (PMN) in endometrial cytology samples, presence of intrauterine fluid, and gravid horn diameter via ultrasonography. Before supplementation, the RPL group showed amino acid imbalance, which was improved by RPL supplementation. There were no significant differences in the onset of luteal activity, percentage of PMN, intrauterine fluid, or the diameter of the uterine horn between the two groups. The vaginal discharge score in the RPL group decreased from 3 to 5 weeks postpartum, whereas that in the CON groups did not decrease. The number of cows with clinical endometritis was lower in the RPL group. Overall, RPL supplementation during the close-up period enhanced vaginal discharge clearance, potentially averting clinical endometritis, but did not affect the first ovulation in dairy cows.

Continuous microalgal culture module and method of culturing microalgae containing macular pigment.

This study established and investigated continuous macular pigment (MP) production with a lutein (L):zeaxanthin (Z) ratio of 4-5:1 by an MP-rich Chlorella sp. CN6 mutant strain in a continuous microalgal culture module. Chlorella sp. CN6 was cultured in a four-stage module for 10 days. The microalgal culture volume increased to 200 L in the first stage (6 days). Biomass productivity increased to 0.931 g/L/day with continuous indoor white light irradiation during the second stage (3 days). MP content effectively increased to 8.29 mg/g upon continuous, indoor white light and blue light-emitting diode irradiation in the third stage (1 day), and the microalgal biomass and MP concentrations were 8.88 g/L and 73.6 mg/L in the fourth stage, respectively. Using a two-step MP extraction process, 80 % of the MP was recovered with a high purity of 93 %, and its L:Z ratio was 4-5:1.

Longitudinal analysis of carotenoid content in preterm human milk.

To describe the variability in carotenoid content of human milk (HM) in mothers of very to extremely low birth weight preterm infants throughout lactation and to explore the relationship between lutein in HM and the occurrence of retinopathy of prematurity (ROP) in preterm infants. We recruited healthy mothers along with their preterm infants that were born at gestational age 24 + 2 to 29 + 6 weeks or with a birth weight under 1500 g and were exclusively breastfed HM. Each participant provided up to 7 HM samples (2-10 ml) on day 0-3 and once a week until 6 weeks. Additionally, when possible, a blood sample was collected from the infant at week 6. Concentrations of the major carotenoids (lutein, zeaxanthin, beta-carotene, and lycopene) in all HM and blood samples were assessed and compared. Thirty-nine mother-infant dyads were included and 184 HM samples and 21 plasma samples were provided. Mean lutein, zeaxanthin, beta-carotene, and lycopene concentration decreased as lactation progressed, being at their highest in colostrum samples (156.9 vs. 66.9 vs. 363.9 vs. 426.8 ng/ml, respectively). Lycopene (41%) and beta-carotene (36%) were the predominant carotenoids in colostrum and up to 2 weeks post-delivery. Inversely, the proportion of lutein and zeaxanthin increased with lactation duration to account for 45% of the carotenoids in mature HM. Lutein accounted for 58% of the carotenoids in infant plasma and only 28% in HM. Lutein content of transition and mature HM did not differ between mothers of ROP and non-ROP infants.Conclusion Carotenoid content of HM was dynamic and varied between mothers and as lactation progressed. Infant plasma displayed a distinct distribution of carotenoids from HM.

Comprehensive Analysis of Lutein and Loroxanthin in Scenedesmus obliquus: From Quantification to Isolation.

Carotenoids are hydrophobic pigments produced exclusively by plants, fungi, and specific microbes. Microalgae are well suited for the production of valuable carotenoids due to their rapid growth, efficient isoprenoid production pathway, and ability to store these compounds within their cells. The possible markets for bio-products range from feed additives in aquaculture and agriculture to pharmaceutical uses. The production of carotenoids in microalgae is affected by several environmental conditions, which can be utilized to enhance productivity. The current study focused on optimizing the extraction parameters (time, temperature, and extraction number) to maximize the yield of carotenoids. Additionally, the impact of various nitrogen sources (ammonia, nitrate, nitrite, and urea) on the production of lutein and loroxanthin in Scenedesmus obliquus was examined. To isolate the carotenoids, 0.20 g of biomass was added to 0.20 g of CaCO3 and 10.0 mL of ethanol solution containing 0.01% (w/v) pyrogallol. Subsequently, the extraction was performed using an ultrasonic bath for a duration of 10 min at a temperature of 30 °C. This was followed by a four-hour saponification process using a 10% methanolic KOH solution. The concentration of lutein and loroxanthin was measured using HPLC-DAD at 446 nm, with a flow rate of 1.0 mL/min using a Waters YMC C30 Carotenoid column (4.6 × 250 mm, 5 µm). The confirmation of carotenoids after their isolation using preparative chromatography was achieved using liquid chromatography-tandem mass spectrometry (LC-MS/MS) with an atmospheric pressure chemical ionization (APCI) probe and UV-vis spectroscopy. In summary, S. obliquus shows significant promise for the large-scale extraction of lutein and loroxanthin. The findings of this study provide strong support for the application of this technology to other species.

Fabrication of Microalgae Oil Vesicles for Drug Delivery Applications.

In this study, it is demonstrated that natural microalgae oils, which contain fatty acid components including docosahexaenoic acid (DHA), could be directly applied to fabricate vesicular structures in aqueous phase through a forced formation process. The microalgae oil vesicles had initial average diameters of 170- 230 nm with negative charges apparently caused by dissociation of the fatty acid components. The vesicles possessed excellent stability with lifetimes for at least 450 days. The formation of the vesicular structures with hydrophilic cores/regions was confirmed by the transmission electron microscopy (TEM) image and successful encapsulation of a hydrophilic material. For encapsulation of a hydrophobic material, lutein, the vesicle size was increased probably due to the insertion of lutein into the hydrophobic vesicular bilayer structures. The analysis of Fourier transform infrared (FTIR) spectroscopy suggested that the vesicular bilayer fluidity was decreased by encapsulating lutein. However, the lutein-encapsulating microalgae oil vesicles still possessed high stability and the vesicular structures could maintain intact even at an environmental temperature up to 60℃. Applicability of the microalgae oil vesicles as drug delivery carriers was also demonstrated by successful encapsulation of curcumin. However, when the loaded curcumin was increased to a certain amount, physical stability of the microalgae oil vesicles was significantly reduced. This is probably because the vesicular structures with only limited spaces for accommodating hydrophobic materials were strongly affected by encapsulating a large amount of curcumin. It is interesting to note that by adding egg L-α-phosphatidylcholine, the curcumin encapsulation-induced instability of the microalgae oil vesicles could be alleviated. The results indicated that vesicular structures could be fabricated from microalgae oils and the microalgae oil vesicles were capable of encapsulating hydrophilic or hydrophobic materials for drug delivery applications. The findings lay a background for further dosage form development of nutritional supplements encapsulated by natural microalgae oils.

Lutein Production and Extraction from Microalgae: Recent Insights and Bioactive Potential.

Microalgae have been reported to be excellent producers of bioactive molecules. Lutein is a pigment reported to have various beneficial effects for humans, and especially for eye well-being. In the current review, we summarize various methods that have been developed to optimize its extraction and bioactivities reported for human health. Several protective effects have been reported for lutein, including antioxidant, anticancer, anti-inflammatory, and cardioprotective activity. This review also reports attempts to increase lutein production by microalgae by changing culturing parameters or by using pilot-scale systems. Genetic engineering lutein production is also discussed. Considering the increasing aging of the worldwide population will create an increased need for lutein, a viable economic and eco-sustainable method to produce lutein is needed to face this market demand.

Site-Directed Mutagenesis of the Chlorophyll-Binding Sites Modulates Excited-State Lifetime and Chlorophyll-Xanthophyll Energy Transfer in the Monomeric Light-Harvesting Complex CP29.

We combine site-directed mutagenesis with picosecond time-resolved fluorescence and femtosecond transient absorption (TA) spectroscopies to identify excitation energy transfer (EET) processes between chlorophylls (Chls) and xanthophylls (Xant) in the minor antenna complex CP29 assembled inside nanodiscs, which result in quenching. When compared to WT CP29, a longer lifetime was observed in the A2 mutant, missing Chl a612, which closely interacts with Xant Lutein in site L1. Conversely, a shorter lifetime was obtained in the A5 mutant, in which the interaction between Chl a603 and Chl a609 is strengthened, shifting absorption to lower energy and enhancing Chl-Xant EET. Global analysis of TA data indicated that EET from Chl a Qy to a Car dark state S* is active in both the A2 and A5 mutants and that their rate constants are modulated by mutations. Our study provides experimental evidence that multiple Chl-Xant interactions are involved in the quenching activity of CP29.

Development of Novel Nanocarriers by Ultrasound and Ethanol-Assisted Soy Protein Isolate: Enhancing the Resistance of Lutein to Environmental Stress.

The aim of this work was to investigate the effects of the processing sequence of ultrasound and ethanol on the physicochemical properties of soy protein isolate (SPI), which were further evaluated for the morphology and stability of SPI-lutein coassembled nanoparticles. The results showed that the sequence of ultrasound followed by ethanol treatment was the optimal one. The samples were subjected to ultrasonication followed by subunit disassembly and reassembly induced by 40% (v/v) ethanol, with the resulting molecular unfolding and subsequent aggregation being attributed to intramolecular hydrogen bonds. The recombined nanoparticles had smaller particle size (142.43 ± 2.91 nm) and turbidity (0.16 ± 0.01), and the exposure of more hydrophobic groups (H0 = 6221.00 ± 130.20) induced a shift of SPI structure toward a more ordered direction. The homogeneous and stable particle provided excellent stability for the loading of lutein. The bioaccessibility (from 25.48 ± 2.35 to 65.85 ± 1.78%) and release rate of lutein were modulated in gastrointestinal digestion experiments. Our discoveries provide a new perspective for the development of combined physicochemical modification of proteins as nanocarriers in functional foods.

Comparison between oral dydrogesterone versus micronized vaginal progesterone gel in clinical outcome within the first HRT-FET cycle: a retrospective analysis.

OBJECTIVE: The purpose of this study is to compare the clinical efficacy of oral dydrogesterone and micronized vaginal progesterone (MVP) gel during the first HRT-FET cycle. METHODS: A retrospective cohort study based on a total of 344 women undergoing their first HRT-FET cycles without Gonadotropin-Releasing Hormone agonist (GnRH-a) pretreatment was conducted. All the cycles were allocated to two groups in the reproductive medical center at the University of Hong Kong-Shenzhen Hospital. One group (n = 193) received oral dydrogesterone 30 mg/d before embryo transfer, while the other group (n = 151) received MVP gel 180 mg/d. RESULTS: The demographics and baseline characteristics of two groups were comparable. We found no statistically significant difference in live birth rate (24.35% vs. 31.13%, P = 0.16), clinical pregnancy rate (34.72% vs. 36.42%, P = 0.74), embryo implantation rate (25.09% vs. 28.36%, P = 0.43), positive pregnancy rate (42.49% vs 38.41%, P = 0.45), miscarriage rate (9.33% vs 3.97%, P = 0.05), or ectopic pregnancy rate (0.52% vs. 0.66%, P = 0.86) between the oral dydrogesterone group and MVP gel group. In the multivariate logistic regression analysis for covariates, medication used for luteal support was not associated with live birth rate (OR = 0.73, 95% CI: 0.32-1.57, P = 0.45). And the different luteal support medication did not have a significant positive association with the live birth rate in the cycles with day 2 embryo transferred (OR = 1.39, 95% CI:0.66-2.39, P = 0.39) and blastocyst transferred (OR = 1.31 95% CI:0.64-2.69, P = 0.46). CONCLUSION: 30 mg/d oral dydrogesterone and 180 mg/d MVP gel revealed similar reproductive outcomes in HRT-FET cycles in the study.

Selective Removal of Chlorophyll and Isolation of Lutein from Plant Extracts Using Magnetic Solid Phase Extraction with Iron Oxide Nanoparticles.

In recent years, there has been a growing interest in plant pigments as readily available nutraceuticals. Photosynthetic pigments, specifically chlorophylls and carotenoids, renowned for their non-toxic antioxidant properties, are increasingly finding applications beyond their health-promoting attributes. Consequently, there is an ongoing need for cost-effective methods of isolation. This study employs a co-precipitation method to synthesize magnetic iron oxide nanoparticles. Scanning electron microscopy (SEM) coupled with energy dispersive spectrometry (EDS) confirms that an aqueous environment and oxidizing conditions yield nanosized iron oxide with particle sizes ranging from 80 to 140 nm. X-ray photoelectron spectroscopy (XPS) spectra indicate the presence of hydrous iron oxide FeO(OH) on the surface of the nanosized iron oxide. The Brunauer-Emmett-Teller (BET) surface area of obtained nanomaterial was 151.4 m2 g-1, with total pore volumes of pores 0.25 cm3 g-1 STP. The material, designated as iron oxide nanoparticles (IONPs), serves as an adsorbent for magnetic solid phase extraction (MSPE) and isolation of photosynthetic pigments (chlorophyll a, lutein) from extracts of higher green plants (Mentha piperita L., Urtica dioica L.). Sorption of chlorophyll a onto the nanoparticles is confirmed using UV-vis spectroscopy, Fourier transform infrared photoacoustic spectroscopy (FT-IR/PAS), and high-performance liquid chromatography (HPLC). Selective sorption of chlorophyll a requires a minimum of 3 g of IONPs per 12 mg of chlorophyll a, with acetone as the solvent, and is dependent on a storage time of 48 h. Extended contact time of IONPs with the acetone extract, i.e., 72 h, ensures the elimination of remaining components except lutein, with a spectral purity of 98%, recovered with over 90% efficiency. The mechanism of chlorophyll removal using IONPs relies on the interaction of the pigment's carbonyl (C=O) groups with the adsorbent surface hydroxyl (-OH) groups. Based on molecular dynamics (MD) simulations, it has been proven that the selective adsorption of pigments is also influenced by more favorable dispersion interactions between acetone and chlorophyll in comparison with other solutes. An aqueous environment significantly promotes the removal of pigments; however, it results in a complete loss of selectivity.

Association between carotenoids and the prevalence of chronic obstructive pulmonary disease in the United States.

BACKGROUND: Previous studies mainly concentrated on examining the correlation between single carotenoids and Chronic obstructive pulmonary disease (COPD). However, these findings have been inconsistent. OBJECTIVES: This study aimed to evaluate both the individual and overall associations of carotenoids with the prevalence of COPD. METHODS: This study comprised 2,939 participants chosen from the National Health and Nutrition Examination Survey (NHANES) 2017-2018. The logistic regression, quantile-based G-computation regression (qgcomp), and Bayesian kernel machine regression (BKMR) models were employed to explore the association between carotenoids and the prevalence of COPD. Mediation analyses were also conducted to explore the underlying mechanism of carotenoids on COPD. RESULTS: Individuals diagnosed with COPD had significantly lower serum carotenoid concentrations than those without COPD. We found a negative relationship between combined carotenoids and the prevalence of COPD, and lutein and zeaxanthin and alpha cryptoxanthin were identified as the main contributors to this negative association. Moreover, eosinophil acted as a mediator in the relationship between lutein and zeaxanthin, alpha cryptoxanthin, and the prevalence of COPD, with mediating proportions of 2.75 % and 3.67 %. CONCLUSION: A negative association was observed between combined carotenoids and COPD prevalence, with lutein and zeaxanthin, and alpha cryptoxanthin identified as the main contributors. Eosinophils could potentially mediate the association between carotenoids and COPD.

The Association between Circulating Carotenoids and Risk of Breast Cancer: A Systematic Review and Dose-Response Meta-Analysis of Prospective Studies.

Carotenoids appear to have anticancer effects. Prospective evidence for the relation between serum carotenoids and breast cancer is controversial. The present systematic review and meta-analysis aimed to investigate the link between circulating carotenoids and the risk of breast cancer. We performed a systematic search of PubMed, Scopus, and Web of Science up to 30 November, 2022. Prospective studies on adults aged ≥18 y that have reported risk estimates for the association between circulating carotenoids and breast cancer risk were considered. Study quality was assessed using the Newcastle-Ottawa Scale. A random-effects model was used for combining studies' risk estimates. Dose-response relations were explored through a 1-stage random-effects model. Fifteen publications (17 nested case-control studies and 1 cohort study) with 20,188 participants and 7608 cases were included. We observed an inverse association between the highest level of circulating total carotenoids (relative risk [RR]: 0.76; 95% confidence interval [CI]: 0.62, 0.93; n = 8), α-carotene (RR: 0.77; 95% CI: 0.68, 0.87; n = 13), ß-carotene (RR: 0.80; 95% CI: 0.65, 0.98; n = 15), ß-cryptoxanthin (RR: 0.85; 95% CI: 0.74, 0.96; n = 11), lycopene (RR: 0.86; 95% CI: 0.76, 0.98; n = 13), and lutein (RR: 0.70; 95% CI: 0.52, 0.93; n = 6) and the risk of breast cancer compared with the lowest level. Additionally, each 10 µg/dL of total carotenoids, α-carotene, ß-carotene, and ß-cryptoxanthin was associated with 2%, 22%, 4%, and 10% lower risk of breast cancer, respectively. This relationship was stronger at lower levels of total carotenoids and ß-cryptoxanthin. The certainty of evidence was rated from very low to low. Most studies were performed among Western nations, which should be acknowledged for extrapolation of findings. Total circulating carotenoids, α-carotene, ß-carotene, ß-cryptoxanthin, lycopene, and lutein seem to be related to a decreased risk of breast cancer. Our findings could have practical importance for public health. This study was registered at PROSPERO as CRD42023434983.

A robust multinutrient kinetic model for enhanced lutein and biomass yields in mixotrophic microalgae cultivation: A step towards successful large-scale productions.

Mixotrophic cultivation holds great promise to significantly enhance the productivities of biomass and valuable metabolites from microalgae. In this study, a new kinetic model is developed, explicitly describing the effect of the most influential environmental factors on both biomass growth and the production of the high-value product lutein. This extensive study of multinutrient kinetics for Tetradesmus obliquus in a mixotrophic regime covers various nutritional conditions. Crucial nutrients governing the model include nitrate, phosphate, and glucose. Using seven state variables and 13 unknown parameters, the model's accuracy was ensured through a well-designed two-factor, four-level experimental setup, providing ample data for reliable calibration and validation. Results accurately predict dynamic concentration profiles for all validation experiments, revealing broad applicability. Optimizing nitrogen availability led to significant increases in biomass (up to fourfold) and lutein production (up to 12-fold), with observed maximum biomass concentration of 6.80 g L-1 and lutein reaching 25.58 mg L-1. Noticeably, the model exhibits a maximum specific growth rate of 4.03 day-1, surpassing reported values for photoautotrophic and heterotrophic conditions, suggesting synergistic effects. Valuable guidance is provided for applying the method to various microalgal species and results are large-scale production-ready. Future work will exploit these results to develop real-time photobioreactor operation strategies.

De Novo Biosynthesis of Lutein in Yarrowia lipolytica.

Lutein is a high-value tetraterpenoid carotenoid that is widely used in feed, cosmetics, food, and drugs. Microbial synthesis of lutein is an important method for green and sustainable production, serving as an alternative to plant extraction methods. However, an inadequate precursor supply and low catalytic efficiency of key pathway enzymes are the main reasons for the low efficacy of microbial synthesis of lutein. In this study, some strategies, such as enhancing the MVA pathway and localizing α-carotene synthase OluLCY within the subcellular organelles in Yarrowia lipolytica, were adopted to enhance the synthesis of precursor α-carotene, which resulted in a 10.50-fold increase in α-carotene titer, reaching 38.50 mg/L. Subsequently, by improving hydroxylase activity with truncated N-terminal transport peptide and locating hydroxylases to subcellular organelles, the final strain L9 producing 75.25 mg/L lutein was obtained. Eventually, a lutein titer of 675.40 mg/L (6.13 mg/g DCW) was achieved in a 5 L bioreactor by adding the antioxidant 2,6-ditert-butyl-4-methylphenol. This study realizes de novo synthesis of lutein in Y. lipolytica for the first time and achieves the highest lutein titer reported so far.

TgLUT1 regulated by TgWRKY10 enhances the tolerance of Torreya grandis to drought stress.

Drought stress is a major abiotic stress which severely reduces the plant growth and limits agricultural productivity. Previous studies have demonstrated that lutein directly synthesized by the carotenoid epsilon-ring hydroxylase gene (LUT1) played crucial roles in regulating drought response. Notwithstanding the myriad studies on LUT1's response to drought stress in certain plant species such as Arabidopsis, the precise function mechanisms within tree species remain ambiguously understood. Our study reveals that under drought stress, TgLUT1, a novel LUT gene instrumental in ß-lutein biosynthesis, was markedly up-regulated in Torreya grandis. Subcellular localization assay indicated that TgLUT1 protein was localized to chloroplasts. Phenotypic analysis showed that overexpression of TgLUT1 enhanced the tolerance of tomato to drought stress. Overexpressing of TgLUT1 increased the values of maximal photochemical efficiency of photosystem II (Fv/Fm), net photosynthetic rate (Pn) and non-photochemical quenching (NPQ), and reduced the accumulation of hydrogen peroxide (H2O2), malondialdehyde (MDA) content and electrolyte leakage percentage in response to drought stress. Furthermore, overexpression of TgLUT1 decreased the stomatal conductance to reduce the water loss rate exposed to drought stress. In addition, yeast one-hybrid assay, dual luciferase assay system and qRT-PCR results showed that TgWRKY10 down-regulated by drought stress inhibited the expression of TgLUT1 by directly binding to the TgLUT1 promoter. Collectively, our results show that TgWRKY10, down-regulated by drought stress, negatively regulates the expression of TgLUT1 to modulate the drought stress response. This study contributes to a more comprehensive understanding of LUT1's function in the stress responses of economically significant forest plants.