The research was conducted from August to October 2025 at the Clinical Pathology Laboratory of Hasanuddin University Hospital in Makassar, Indonesia. It used a pretest–posttest control-group design without placebo treatment. Eligible participants were adults without diabetes mellitus who had abdominal obesity, defined as a waist circumference of at least 80 cm for women and 90 cm for men. People with a current infection or acute inflammation and those using antioxidant supplements or vitamins were excluded.

Participants were assigned systematically according to their arrival sequence rather than through true randomization. Those arriving with odd sequence numbers received astaxanthin, while those arriving with even sequence numbers served as untreated controls. The intervention consisted of 4 mg of astaxanthin per day for four weeks. Participants in both groups were asked to maintain their usual diet and physical activity and avoid other supplements. Each group included 17 women and four men, and no adverse reactions were reported during the study period.

Blood samples were collected at baseline and again on day 28. Before baseline sampling, participants fasted for 8–10 hours overnight. Researchers measured blood pressure, body mass index and waist circumference, collected 5 mL of blood for fasting plasma glucose testing, and conducted a two-hour oral glucose tolerance test. Serum was separated and stored at −20 °C before myeloperoxidase concentrations were measured by enzyme-linked immunosorbent assay at the Hasanuddin University Medical Research Center.

Among participants receiving astaxanthin, the reported median serum myeloperoxidase concentration fell from 20.30 pg/mL before supplementation to 17.29 pg/mL after four weeks. The corresponding interquartile ranges were 16.16 and 10.23 pg/mL. The before-and-after difference was statistically significant according to a Wilcoxon test, with p = 0.014. This was an analysis of changes within the supplemented group rather than a reported direct comparison of treatment effects between groups.

In the untreated control group, the reported median myeloperoxidase concentration changed from 19.94 pg/mL at baseline to 17.49 pg/mL after four weeks, with interquartile ranges of 7.17 and 9.14 pg/mL. That within-group change was not statistically significant, with p = 0.876. The source does not report a direct between-group treatment-effect estimate or a confidence interval for the difference in changes.

Myeloperoxidase is an enzyme produced primarily by neutrophils and also by other innate immune cells, including macrophages and monocytes. The study notes that plasma myeloperoxidase levels can be elevated in people with obesity and that increased infiltration of neutrophils and macrophages into adipose tissue may contribute to its release into circulation. Under pathological conditions, excessive enzyme release may increase oxidative stress and contribute to inflammation and tissue damage. Astaxanthin was investigated because of its reported antioxidant and anti-inflammatory properties, but the human experiment did not directly measure the proposed cellular pathway.

One possible explanation offered by the researchers was that astaxanthin’s antioxidant activity could reduce oxidative stress and thereby lessen proinflammatory activity among macrophages and monocytes in adipose tissue, potentially decreasing their production of myeloperoxidase. This mechanism remained a proposal rather than a pathway directly established by the study. Separate experiments in rats with carbon tetrachloride-induced liver injury and mice with Helicobacter pylori-induced gastric mucosal inflammation reported lower tissue myeloperoxidase activity after astaxanthin supplementation, but those animal findings do not by themselves demonstrate clinical benefits in humans.

The study has important constraints on interpretation. Systematic allocation rather than randomization may have introduced selection bias, and the open-label design meant that placebo effects or behavioral changes could not be completely ruled out. The trial was also registered retrospectively with the Thai Clinical Trials Registry on 18 March 2026, after completion of data collection. Its scope was limited to 42 adults with abdominal obesity who did not have diabetes, a four-week intervention period, and a biomarker-based outcome. The authors said further research is needed to assess different doses, longer treatment periods and populations with more severe obesity.

Subject of Research: Effects of four-week astaxanthin supplementation on serum myeloperoxidase in adults with abdominal obesity

Article Title: Astaxanthin supplementation is associated with a reduction in serum myeloperoxidase levels in subjects with abdominal obesity

Article References: Mulyamin, W., Kurniawan, L. B., Zainuddin, A. A., Leman, Y., Aminuddin, A., Pangkahila, W., Djabir, Y. Y., & As’ad, S. (2026). Astaxanthin supplementation is associated with a reduction in serum myeloperoxidase levels in subjects with abdominal obesity. Pharmacia, 73, Article e200901. https://doi.org/10.3897/pharmacia.73.e200901

Image Credits: AI Generated

DOI: 10.3897/pharmacia.73.e200901

Keywords: astaxanthin, abdominal obesity, myeloperoxidase, serum biomarkers, inflammation, oxidative stress, quasi-experimental study, supplementation, neutrophils, macrophages, associated, reduction

The molecule’s structure explains both its power and its problems. Astaxanthin possesses an extended conjugated polyene chain terminated by two polar rings, each bearing hydroxyl and keto groups. This architecture lets the molecule span lipid membranes, anchoring at the surface while the chain sits within the bilayer, where it can intercept reactive oxygen species on both the aqueous and lipid sides. But the polyene chain is also the site of vulnerability: each double bond can undergo oxidation, isomerization or cleavage when exposed to oxygen, elevated temperature or ultraviolet radiation. For food formulators, this means that an astaxanthin-rich ingredient can lose its color and its bioactivity during baking, pasteurization or months of retail shelf storage, a constraint that has historically kept the pigment confined to high-value niches such as aquafeed.

Not all astaxanthin is chemically identical, and the review places unusual emphasis on stereochemistry. The molecule exists in three stereoisomeric configurations, and the 3S,3’S form, produced naturally by the green microalga Haematococcus pluvialis, is described as the predominant bioactive configuration. Synthetic astaxanthin, manufactured by chemical synthesis for the feed industry, arrives as a mixture of isomers with different biological behavior. Beyond chirality, the geometry of the central chain matters too: the all-E (trans) configuration dominates in natural sources, but processing can convert a fraction of it to Z (cis) isomers, which are more soluble and, in some contexts, more bioavailable. Work cited in the review found that Z-isomer-rich diets enhanced egg yolk pigmentation in laying hens more effectively than all-E-rich diets, a finding that turns isomerization from a degradation problem into a potential design tool.

Esterification adds another layer of complexity. In Haematococcus and in shrimp by-products, much of the astaxanthin occurs as monoesters and diesters, with fatty acids attached to the hydroxyl groups on the terminal rings. These esters are generally more stable than the free molecule, and the attached fatty acids can influence both antioxidant performance and digestibility. Chromatographic analyses of shrimp and algal extracts have mapped these ester profiles in detail, and the review argues that understanding the ester composition of a given source is essential for predicting how it will behave in a food matrix. Free astaxanthin from the yeast Phaffia rhodozyma, by contrast, is unesterified, which simplifies formulation but may alter its stability and uptake.

Where does industrial astaxanthin actually come from? The review surveys three biological workhorses. Haematococcus pluvialis, a freshwater microalga that accumulates astaxanthin esters in thick-walled cyst cells when stressed by light and nutrient deprivation, remains the richest natural source and the dominant route for human nutraceutical products. The red yeast Phaffia rhodozyma (also called Xanthophyllomyces dendrorhous) offers fast fermentation in bioreactors and free, unesterified pigment, making it attractive for feed and increasingly for food applications. The bacterium Paracoccus carotinifaciens provides a dried cell powder used directly in animal diets. Meanwhile, shrimp processing waste, heads and shells that would otherwise be discarded, represents a circular-economy opportunity, with ultrasound-assisted extraction into vegetable oils, including extra virgin olive oil, demonstrating both good recovery and successful incorporation into functional foods with strong consumer acceptance.

Getting the pigment out of these tough biological matrices is half the battle. Haematococcus cysts are notoriously resistant, encased in a robust cell wall that must be disrupted before any solvent can reach the pigment. The review catalogs a progression of cell-disruption and extraction technologies: high-pressure homogenization, which physically fractures the cyst wall; pulsed electric fields, which permeabilize membranes and can trigger enzymatic processes that loosen the matrix; ultrasound-assisted extraction, which uses cavitation to accelerate mass transfer; and subcritical fluid extraction, which has been applied to yeast biomass after cell wall breaking. On the solvent side, green chemistry is displacing petrochemical solvents. Supercritical carbon dioxide with ethanol as a co-solvent extracts astaxanthin and lutein from red-phase algal biomass without leaving toxic residues, while deep eutectic solvents and ionic liquids have shown strong performance against conventional organic solvents, including acidic deep eutectic systems applied directly to Haematococcus biomass. Notably, one strategy recovered astaxanthin at high yield directly from wet algal biomass without any drying pretreatment, a potentially significant energy saving given how expensive dewatering microalgae can be.

Extraction, however, only delivers a fragile molecule into a hostile world, and the review devotes substantial attention to keeping astaxanthin intact. Microencapsulation is the workhorse: embedding the pigment in protective matrices of proteins, polysaccharides or lipid carriers shields it from oxygen and light. Researchers have produced food-grade microcapsules using vibrating nozzle technology, which generates uniform particles suitable for large-scale production, and have shown that the fatty acid composition of the encapsulating oil affects the kinetic stability of both astaxanthin and co-encapsulated alpha-tocopherol during storage. Stability testing in model food systems confirms the practical stakes, with incorporation and retention varying widely depending on the matrix, processing conditions and packaging. The message for manufacturers is that astaxanthin cannot simply be stirred into a recipe; it must be engineered into the product.

The most technically ambitious frontier is nanoscale delivery. Because astaxanthin is lipophilic and poorly water-soluble, its oral bioavailability is low, limited by micellar solubilization in the gut and by degradation en route. Nano-delivery systems attack this bottleneck directly. Nanoemulsions, nanoliposomes, lipid nanoparticles and polymeric nanocarriers can disperse the pigment in aqueous foods, protect it during digestion and improve its uptake by intestinal cells. The review highlights examples with almost pharmaceutical precision: a microenvironment-responsive pod-structured nanocarrier designed to release astaxanthin in the inflamed gut, where it ameliorated inflammatory bowel disease in experimental models, and a nano-lipidic astaxanthin formulated in a thermoreversible gel that showed efficacy in a model of drug-induced Parkinsonism. In the cosmetic sphere, astaxanthin-zeaxanthin nanoemulsions have been formulated into radiance serums evaluated for stability and anti-wrinkle activity, building on earlier clinical work showing cosmetic benefits and topical antioxidant protection for skin.

In animal agriculture, astaxanthin’s roles are both aesthetic and physiological. In aquaculture, it is indispensable: salmonids and other farmed fish cannot synthesize carotenoids and must obtain pigmentation from their diet, and the pigment also supports reproduction and survival. Supplementation studies show broader benefits, including enhanced hemato-biochemical parameters and innate immunity in Asian seabass, improved growth, immunity and tissue composition in largemouth bass, and better antioxidant capacity, immunity and disease resistance in coral trout. In poultry, dietary astaxanthin from red yeast improved growth performance, meat quality and even reduced fecal noxious gas emissions in broilers, while microalgae-derived astaxanthin improved cytoprotective capacity in the intestines of heat-stressed birds and benefited the gut health of yellow-feathered broilers. In laying hens, moderate and high dose supplementation trials have assessed responses in yolk pigmentation and physiology, with Z-isomer-rich formulations outperforming conventional all-E forms in yolk color enhancement.

The livestock evidence extends to mammals facing one of modern farming’s chronic challenges: heat stress. Astaxanthin supplementation ameliorated simulated heat stress in Sirohi goats by regulating physio-biochemical responses, altered muscle antioxidant activity and meat quality in broilers exposed to high ambient temperatures, reduced oxidative stress in sows with positive effects on piglet growth, improved antioxidant status and immunity in growing buffalo heifers when paired with copper, and even preserved sperm quality and antioxidant capacity in stored ram semen. Taken together, the review frames astaxanthin as a versatile tool for an agro-food sector grappling with climate pressure, consumer demand for natural ingredients and the valorization of processing waste. The obstacles that remain, cost-competitive production, scalable green extraction, and delivery systems that survive real-world food processing, are precisely the areas where the 2000 to 2025 literature shows the fastest movement, suggesting that the molecule once prized mainly for making salmon pink may soon be engineered into a far wider range of foods, feeds and therapies.

Subject of Research: Advances in astaxanthin sources, green extraction, stabilization, nano-delivery systems and nutritional applications in the agro-food industry

Article Title: Astaxanthin in the agro-food industry: advances in sources, processing, delivery systems, and nutritional applications

Article References: Qiang, J., Liao, S., Zhang, R., Piao, Y., Yu, M., Zhang, J., & Ren, L. (2026). Astaxanthin in the agro-food industry: advances in sources, processing, delivery systems, and nutritional applications. Food Science and Biotechnology. https://doi.org/10.1007/s10068-026-02345-z

Image Credits: AI Generated

DOI: 10.1007/s10068-026-02345-z

Keywords: astaxanthin, carotenoid, antioxidant, Haematococcus pluvialis, green extraction, nano-delivery systems, bioavailability, microencapsulation, aquaculture, animal feed, nutraceuticals, food science

TRPV channels are non-selective cation channels, meaning they form pores in cell membranes that allow positively charged ions, chiefly calcium and sodium, to flow into cells. They are best known for their roles in sensing heat, pain, and osmotic pressure, but the review emphasizes that they also participate in metabolic regulation. In diabetes, the chronic high blood sugar characteristic of the disease alters the expression of these channels and reduces calcium influx through them. That disturbance is not a minor biochemical footnote. Calcium entering a cell through TRPV channels acts as a second messenger, triggering cascades that influence how the cell responds to stress, how it communicates with the immune system, and how it maintains its own energy balance. When that signaling goes awry, the consequences ripple outward into tissues throughout the body.

The review identifies three downstream pathways as the critical links between TRPV dysfunction and diabetic tissue damage. The first is NF-κB, a transcription factor that functions as a master switch for inflammation. When NF-κB is activated, cells churn out inflammatory signaling molecules such as tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6, which sustain the low-grade chronic inflammation that is a hallmark of diabetes and its complications. The second pathway involves TGF-β, a growth factor that drives fibrosis, the pathological accumulation of extracellular matrix proteins that stiffens and eventually destroys organs such as the kidneys, heart, and liver. Diabetic kidney disease, in particular, is characterized by fibrotic remodeling driven by TGF-β signaling. The third pathway is AMPK, an energy-sensing enzyme that acts as a cellular fuel gauge, promoting metabolic homeostasis by regulating glucose uptake, fat metabolism, and mitochondrial health.

What makes the new review notable is its attempt to connect these three pathways to TRPV channel modulation by specific plant compounds. Terpenes are built from repeating five-carbon isoprene units, and their oxygenated derivatives, the terpenoids, constitute one of the largest and most structurally diverse families of natural products on Earth. The authors catalog preclinical work on several prominent members of the family, including d-limonene, the monoterpene that dominates citrus peel oil; p-cymene, found in thyme and cumin; and carvacrol, the pungent phenolic monoterpene in oregano. In diabetic animal models, these compounds have been reported to improve glucose tolerance and lower blood glucose levels through a variety of molecular mechanisms, some of which the authors propose may intersect with TRPV channel function.

The evidence for direct TRPV modulation by terpenoids is strongest for certain well-studied compounds. Capsaicin, the vanilloid from chili peppers, is the archetypal TRPV1 agonist, and the review notes that other plant molecules interact with the same channel in more subtle ways. The monoterpene (-)-carvone has been identified as a novel TRPV1 agonist in electrophysiological studies, while menthol, another familiar terpene, exerts reciprocal effects on thermosensation through its actions on TRPV1 and the related cold-sensing channel TRPM8. These interactions matter because TRPV1 activity has been implicated in neuroendocrine regulation of metabolism, in vascular function, and in the fibrotic processes that damage diabetic organs. Modulating the channel, the review argues, initiates a molecular cascade that can either upregulate or downregulate AMPK, TGF-β, and NF-κB signaling depending on the context.

Beyond the monoterpenes, the review surveys a range of larger terpenoids with documented effects on the diabetic phenotype. Triterpenoid acids such as ursolic acid, oleanolic acid, and betulinic acid have shown renoprotective and cardioprotective effects in diabetic rodent models, with mechanisms that include AMPK activation and suppression of TGF-β-driven fibrosis. Carnosic acid from rosemary has been reported to attenuate diabetic retinopathy through the SIRT1 signaling pathway, while carnosol increases glucose uptake in skeletal muscle cells by promoting AMPK-dependent translocation of the GLUT4 glucose transporter to the cell surface. Sesquiterpene lactones such as parthenolide have alleviated fibrosis by inhibiting the NF-κB/TGF-β/Smad signaling axis, and micheliolide has ameliorated diabetic kidney disease in db/db mice by suppressing renal inflammation.

On the clinical side, the evidence base is thinner but not empty. Astaxanthin, a tetraterpenoid pigment responsible for the pink color of salmon and shrimp, stands out as the compound with the most human trial data in type 2 diabetes. Multiple clinical studies have reported reductions in diabetic biomarkers including glycated hemoglobin, fasting glucose, and SIRT1 levels in patients taking astaxanthin supplements. Human pharmacokinetic data also exist for smaller terpenes such as menthol and thymol, confirming that these compounds are absorbed systemically and reach measurable concentrations in the bloodstream. However, the authors are careful to note that clinical evidence specifically linking terpenoid administration to TRPV modulation in metabolic syndrome remains limited, a gap they identify as a priority for future research.

The review’s most valuable contribution may be its epistemological honesty. Rather than presenting all terpenoid-TRPV connections as established fact, the authors explicitly distinguish between experimentally supported channel modulation, mechanistic associations that are plausible but unproven, and relationships that require further validation. This matters because the field of natural products research has long struggled with overclaiming, with correlations between plant compound consumption and health outcomes frequently presented as causal mechanisms. By laying out which links rest on direct electrophysiological data, which rest on downstream pathway measurements, and which are purely speculative, the review provides a framework that other researchers can use to design targeted experiments rather than simply accumulating more correlative studies.

The translational challenges ahead are substantial. Terpenes and terpenoids often suffer from poor bioavailability, rapid metabolism, and low aqueous solubility, which is why a significant portion of the recent literature the review cites involves nanoformulations designed to improve delivery of compounds such as ursolic acid, limonene, and eugenol. Dosing also presents a puzzle, since many terpenoids exhibit hormetic or biphasic effects, activating channels at low concentrations and inhibiting them at high ones. And because TRPV channels are expressed throughout the nervous system, vasculature, and immune system, any therapeutic strategy targeting them must contend with the possibility of off-target effects on thermoregulation, pain sensation, and blood pressure. The authors argue that pathway-specific interventions are urgently needed in diabetes, and that TRPV channels represent an underexploited target, but they stop short of claiming that terpenoids are ready for clinical deployment.

Still, the convergence of evidence is intriguing. Diabetes affects more than half a billion people worldwide according to the International Diabetes Federation, and its fibrotic and inflammatory complications remain incompletely treated by existing drugs. If plant terpenoids can indeed be harnessed to restore TRPV channel function and thereby rebalance NF-κB, TGF-β, and AMPK signaling, they would offer a multi-target approach that differs fundamentally from single-molecule pharmaceuticals. The review by Awate and Kaur does not prove that this therapeutic vision will be realized, but it maps the terrain with unusual clarity, identifying exactly which molecular connections are solid, which are shaky, and which experiments would settle the question. For a field often criticized for hype, that kind of disciplined map may be the most valuable compound of all.

Subject of Research: Modulation of TRPV ion channels by plant terpenes and terpenoids in diabetes, inflammation, and fibrosis

Article Title: Terpenes and terpenoids modulating TRPV channels in diabetes: role in fibrosis and inflammatory signaling

Article References: Awate, S. A., & Kaur, G. (2026). Terpenes and terpenoids modulating TRPV channels in diabetes: role in fibrosis and inflammatory signaling. Molecular Biology Reports, 53(1), Article 1695. https://doi.org/10.1007/s11033-026-12875-8

Image Credits: AI Generated

DOI: 10.1007/s11033-026-12875-8

Keywords: diabetes, TRPV channels, terpenes, terpenoids, NF-kappaB, TGF-beta, AMPK, fibrosis, inflammation, astaxanthin, hyperglycemia, phytotherapy

The new platform, described in the journal Materials Today Bio, is built from hyaluronic acid, a naturally occurring polysaccharide already familiar from cosmetic and biomedical applications. The key insight lies in the chemistry of crosslinking. Hyaluronic acid, with its abundant carboxyl groups, readily coordinates with multivalent cations such as calcium ions, forming a three-dimensional hydrogel network reinforced by hydrogen bonds in humid conditions. But when the gel encounters tissue fluid rich in monovalent sodium and potassium ions, ligand exchange displaces the pre-chelated calcium and the network rapidly falls apart. This dynamic, switchable coordination network gives the microneedles a rare combination of properties: enough mechanical strength to pierce the oral epithelium when dry, and near-instant disintegration once exposed to the salty microenvironment of ulcerated tissue.

The design inspiration came from nematocysts, the microscopic harpoon-like organelles that jellyfish use to discharge venom in response to osmotic pressure. To mimic this triggered-release strategy, the researchers first constructed drug-loaded nanofibers from glycyrrhizic acid, a natural saponin that self-assembles into long-range ordered structures with internal hydrophobic domains. Using a low-frequency acoustic resonance technique operating at 55 hertz, they co-assembled glycyrrhizic acid with two complementary plant-derived therapeutics: baicalein, a flavonoid that disrupts bacterial cell walls and inhibits bacterial DNA synthesis, and astaxanthin, a potent carotenoid antioxidant that scavenges reactive oxygen species and promotes tissue repair. The resulting nanofibers measured just 3 to 4 nanometers in diameter but stretched up to 5 micrometers in length, an extraordinary aspect ratio of 1250, with surface zeta potentials exceeding 40 millivolts that keep the suspensions physically stable.

Encapsulation within the nanofibers solved one of the most stubborn problems in phytochemical medicine: poor water solubility. Free baicalein and astaxanthin barely dissolve in aqueous media, but once loaded into the glycyrrhizic acid fibers their apparent solubilities rose to 775.50 and 95.16 micrograms per milliliter, corresponding to enhancements of 127.5-fold and 213.7-fold respectively. Because the nanofibers carry abundant surface carboxyl groups, they behave like anionic polymers and can themselves participate in calcium-mediated gelation, becoming woven into the hyaluronic acid matrix rather than merely suspended within it. When calcium chloride solution was added, a stable, self-healing gel formed within one minute, confirmed by scanning electron microscopy and rheological testing that revealed the characteristic thixotropic behavior of an electrostatically crosslinked network.

The finished microneedle patch, designated GA@BA&Ast MNs, was cast in polydimethylsiloxane molds using vacuum centrifugal casting. Each 10 by 10 millimeter patch carries a 15 by 15 array of needles, 600 micrometers tall with 300-micrometer bases, dimensions chosen to match the anatomy of the oral epithelium so the tips cross the stratum corneum without damaging deeper tissue. Mechanical testing showed the composite needles were 1.56 times stronger than pure hyaluronic acid microneedles, comfortably exceeding the 0.15-newton threshold required for epithelial penetration. Confocal imaging of fluorescently labeled patches confirmed uniform drug distribution throughout the tips, and in rat tissue the needles delivered their cargo to depths of at least 220 micrometers, reaching the deep epithelial layers that topical formulations cannot access.

Once inserted, the transformation was dramatic. In dissolution experiments simulating the oral environment at 37 degrees Celsius and high humidity, the needle tips vanished within 2 minutes, and quantitative analysis showed that more than 85 percent of the microneedle volume had decomposed within 20 minutes, leaving minimal remnants. Spectroscopic analysis with ATR-FTIR and X-ray photoelectron spectroscopy traced the mechanism: sodium ions from the tissue fluid infiltrate the matrix and associate with the hyaluronic acid carboxylates, initiating network rearrangement, while hyperosmotic conditions further drive hydration, swelling and diffusion. Compared with chitosan-based microneedles, the release rates of astaxanthin and baicalein were enhanced by factors of 15.49 and 596.31 respectively. Crucially, the released nanofibers were then rapidly taken up by surrounding cells: within 30 minutes, the absolute amounts of astaxanthin and baicalein absorbed by oral tissue exceeded those from chitosan microneedles by 91.71-fold and 401.47-fold.

Laboratory assays revealed how the two drugs divide the therapeutic labor. In endothelial cell models, the combined nanofibers drove a scratch-wound closure rate of 87.8 percent within 24 hours, significantly outperforming astaxanthin alone at 56.4 percent, and promoted the formation of orderly tubular networks on Matrigel, indicating robust pro-angiogenic activity. The dual-drug formulation also showed the strongest scavenging of reactive oxygen species in inflamed macrophages. On the antimicrobial front, baicalein proved to be the core active component: plate assays confirmed that the released nanofibers killed and inhibited both Escherichia coli and Staphylococcus aureus, while neither hyaluronic acid nor glycyrrhizic acid alone had significant effect. In lipopolysaccharide-stimulated macrophages, the combination produced the greatest reductions in the pro-inflammatory cytokines interleukin-6 and tumor necrosis factor-alpha among all tested groups.

The decisive test came in a rat model of oral ulceration induced by acetic acid chemical burn. Over a seven-day treatment period, ulcers treated with the full microneedle system achieved 77.3 percent wound closure, compared with just 25.5 percent natural healing in untreated animals, 34.9 percent with blank microneedles and 54.3 percent with baicalein-only patches. Macroscopically, the treated ulcers regained a healthy pink color, a sign of rapid revascularization absent in the controls. Histological examination told the same story: while untreated animals remained at the early granulation stage, the combination-treated tissue showed a smooth, continuous epithelial layer covering the wound with minimal inflammatory infiltration, hallmarks of the final maturation and remodeling phase of healing. Masson’s trichrome staining revealed uniformly organized collagen fibers resembling normal mucosa, and immunohistochemistry showed collagen deposition enhanced by 41 percent and vascular endothelial growth factor expression boosted by 47 percent relative to model controls, alongside elevated phosphorylation of PI3K and Akt, suggesting the pro-angiogenic effect runs through this well-known signaling pathway.

Safety results were equally encouraging. Major organs from treated animals showed intact architecture without inflammation, necrosis or fibrosis, the hemolysis rate stayed below the 5 percent acceptance criterion, and endothelial cell viability remained above 90 percent after exposure to patch extracts. Because the formulation relies on plant-derived compounds rather than antibiotics or corticosteroids, it sidesteps the side effects and resistance concerns associated with conventional pharmacological treatments. The researchers position the platform as a universal delivery system for hydrophobic small-molecule drugs, one whose osmolality-triggered disintegration requires no external stimulus and is tailored specifically to the wet, hyperosmotic and mechanically active environment of the mouth. If the approach translates to the clinic, the humble jellyfish sting, refined over hundreds of millions of years of evolution, may offer relief to the millions of people who suffer each year from the raw, painful lesions of oral ulcers, and potentially to patients with oral fibrosis and oral cancer as well.

Subject of Research: Osmolality-responsive dissolving microneedles for oral ulcer drug delivery

Article Title: Hyaluronic acid-based osmolality-responsive immediate-release microneedles co-loading baicalein and astaxanthin for oral ulcer therapy

Article References: Yang, J., Shi, K., Wang, J., Liu, H., Zhang, Y., Guang, X., Wang, S., Lei, W., Wang, Y., Tan, M., Ma, X., & Wu, H. (2026). Hyaluronic acid-based osmolality-responsive immediate-release microneedles co-loading baicalein and astaxanthin for oral ulcer therapy. Materials Today Bio, 41, Article 103702. https://doi.org/10.1016/j.mtbio.2026.103702

Image Credits: AI Generated

DOI: 10.1016/j.mtbio.2026.103702

Keywords: microneedles, oral ulcers, hyaluronic acid, drug delivery, baicalein, astaxanthin, glycyrrhizic acid, nanofibers, biomimetic, osmolality-responsive, wound healing, anti-inflammatory

Type 2 diabetes mellitus is the dominant form of a disease that now affects hundreds of millions of people worldwide, with prevalence projected to climb steeply over the coming decades. The condition is defined by insulin resistance—tissues failing to respond properly to the hormone insulin—combined with a relative shortfall in insulin production, producing chronically elevated blood sugar. Over time, that hyperglycemia damages blood vessels and organs, driving complications ranging from kidney disease and retinopathy to cardiovascular disease. Standard therapies such as metformin, sulfonylureas, and thiazolidinediones can be effective, but they often carry side effects including gastrointestinal distress and weight gain, prompting researchers to search for safer dietary adjuncts.

The two ingredients at the heart of the new study come from very different corners of the natural products world. Astaxanthin is a lipophilic carotenoid antioxidant produced by the microalga Haematococcus pluvialis, the only approved source for human consumption, as well as by krill, copepods, and the animals that eat them. Since the 1990s it has attracted scientific attention for its potent antioxidant, anti-inflammatory, and organ-protective properties, and prior research has suggested it can preserve pancreatic beta-cell function, ease insulin resistance, and enhance insulin secretion. Fish oil, meanwhile, delivers omega-3 polyunsaturated fatty acids—chiefly EPA and DHA—which are well documented to reduce inflammation, modulate blood lipids, and improve insulin sensitivity.

Crucially, fish oil also appears to boost the bioavailability of astaxanthin, and earlier work has hinted at synergistic effects when the two are co-administered. Yet no one had rigorously tested whether combining them produces a genuine hypoglycemic benefit. To find out, the research team created an astaxanthin oil–fish oil complex, blending astaxanthin oil containing 10 percent astaxanthin with fish oil rich in EPA and DHA ethyl esters, and put it through a two-pronged battery of tests: insulin-resistant human liver cells in the lab, and mice engineered to develop type 2 diabetes through a high-fat diet.

In the cellular experiments, the team first established an insulin-resistant model using HepG2 liver cells, which are a standard workhorse for studying glucose metabolism. Cells exposed to elevated glucose and insulin showed sharply reduced glucose consumption, mimicking the insulin-resistant state seen in diabetes. When the researchers treated these cells with the complex at a 1:12 ratio of astaxanthin oil to fish oil, the results were striking. At the highest concentration, glucose consumption surged by 94.24 percent compared with untreated model cells—a dramatic improvement that neither ingredient achieved alone at equivalent doses.

The complex also reshaped the activity of key metabolic enzymes. Hexokinase, which catalyzes the first step of glycolysis by phosphorylating glucose, was significantly and dose-dependently elevated by the combination, even though neither astaxanthin oil nor fish oil individually moved the needle. Pyruvate kinase, another glycolytic regulator, was similarly restored. Meanwhile, activity associated with glucose-6-phosphatase—a marker of glucose production through gluconeogenic and glycogenolytic pathways, which was abnormally elevated in the resistant cells—was suppressed more strongly by the complex than by either component alone. Cellular glycogen stores, depleted in the insulin-resistant state, rebounded most robustly with the combination treatment.

Oxidative stress, a major driver of diabetic complications, also came under attack. Insulin-resistant cells showed depressed superoxide dismutase activity and elevated malondialdehyde, a marker of lipid peroxidation. The medium-dose complex raised SOD and catalase activities by 43.43 percent and 10.63 percent respectively while cutting malondialdehyde by 35.05 percent; the high dose pushed those improvements further, lifting SOD by 66.84 percent and slashing lipid peroxidation by more than 40 percent. The authors attribute this to the complementary chemistry of the two ingredients: astaxanthin’s exceptional free-radical-scavenging ability paired with the omega-3 fatty acids’ anti-inflammatory action.

The animal experiments told a consistent story. In mice made diabetic and insulin-resistant through two months on a high-fat diet, four weeks of daily oral treatment with the high-dose complex reduced fasting blood glucose from 12.76 to 8.81 millimoles per liter—a reduction comparable to that achieved with metformin, the standard positive control. Oral glucose tolerance tests showed the complex groups clearing glucose from the bloodstream faster than mice given either ingredient alone. Serum analysis revealed a broad metabolic cleanup: in the high-dose group, LDL cholesterol, total cholesterol, and triglycerides fell by 61.6, 26.5, and 53.3 percent respectively, while HDL cholesterol rose by 57.2 percent. Liver injury markers ALT and AST dropped by roughly 40 percent, signaling meaningful hepatic protection.

Under the microscope, the differences were visible to the naked eye of a pathologist. Livers from untreated diabetic mice were disordered and fatty, riddled with vacuoles and inflammatory infiltrates, while those from the high-dose complex group looked strikingly close to healthy tissue. Pancreatic islets, shrunken and blurred in the diabetic controls, regained their shape and cellular density with treatment. Hepatic antioxidant defenses told the same quantitative story: glutathione levels soared by 180.92 percent and catalase activity by 66.67 percent in the high-dose group compared with untreated diabetic mice, alongside a marked drop in malondialdehyde.

The authors are careful to note the limits of their work. The insulin-resistant cell model is an operational approximation that did not directly measure insulin signaling or glucose transport, and mouse models cannot fully capture human diabetes pathophysiology. Mechanisms such as glucose uptake, GLUT expression, and PI3K/Akt signaling remain to be clarified in more physiologically relevant systems. Still, the pattern is compelling: across every metric tested—glucose consumption, glycolytic enzyme activity, glycogen storage, oxidative stress, blood lipids, liver enzymes, and tissue architecture—the astaxanthin–fish oil complex consistently outperformed its individual components. If future studies confirm these effects in humans, the pink pigment of the sea and the omega-3 fats of fish oil could become a powerful dietary alliance in managing one of the world’s fastest-growing diseases.

Subject of Research: Hypoglycemic effects of an astaxanthin oil and fish oil complex in cellular and mouse models of type 2 diabetes

Article Title: Hypoglycemic Effect of Astaxanthin Oil–Fish Oil Complex in Mice With Type 2 Diabetes

Article References: Lin, Z., He, J., Xi, X., Zhang, Y., Le, Q., Guo, Y., Fang, H., Jin, W., Chen, H., Chen, S., & Chen, W. (2026). Hypoglycemic Effect of Astaxanthin Oil–Fish Oil Complex in Mice With Type 2 Diabetes. Food Science & Nutrition, 14(10), Article e72410. https://doi.org/10.1002/fsn3.72410

Image Credits: AI Generated

DOI: 10.1002/fsn3.72410

Keywords: astaxanthin, fish oil, type 2 diabetes, insulin resistance, omega-3 fatty acids, hypoglycemic effect, oxidative stress, HepG2 cells, blood glucose, dyslipidemia, nutraceuticals, carotenoids

The scale of the challenge is enormous. Population growth and rapid economic development have intensified global water shortages, while wastewater streams from domestic, municipal, industrial, agricultural and aquaculture activities carry nitrogen, phosphorus, heavy metals and high chemical oxygen demand into the environment. Conventional treatment processes, while useful, come with significant drawbacks, including greenhouse gas emissions, high energy requirements and nutrient-rich discharges. The review emphasizes that to build a sustainable future and support the circular economy, waste should be converted into valuable resources for recycling and reuse rather than simply discarded. Microalgae, with their ability to fix carbon dioxide and strip pollutants from water, offer an elegant biological solution that produces something useful in the process.

Among the many genera studied, Chlorella species stand out for their versatility in treating municipal wastewater at multiple stages, from pre-settling to post-activated sludge. But the review highlights that the real magic often happens in partnership. Many microalgae form symbiotic relationships with aerobic and anaerobic bacteria and fungi, and these consortia can dramatically improve treatment outcomes. In one striking example, bacteria coexisting with Chlorella pyrenoidosa in soybean processing wastewater enhanced the biodegradation of glucose, nitrogen, phosphorus and chemical oxygen demand. Bacterial partners synthesize antibiotics, growth stimulants, micronutrients, siderophores and vitamin B12 that support algal growth while protecting the algae from pathogens. In poultry wastewater, bacteria reduced nitrogen and organic matter while releasing carbon dioxide that the algae consumed, with the algae reciprocating with dissolved oxygen.

The technical details of cultivation matter enormously to the economics. Microalgae are grown in open raceway ponds or closed photobioreactors, using water, atmospheric carbon dioxide and nutrient-rich media. Because water itself contributes heavily to operational costs, substituting wastewater as the growth medium is a major economic lever. Yet raw wastewater can be too harsh for sensitive strains, so pretreatment or dilution is often essential. Studies cited in the review show that titanium oxide plus intense pulse light pretreatment of swine wastewater boosted growth of Tribonema and Synechocystis species, while diluting textile wastewater to 50 percent increased Chlorella vulgaris biomass suitable for biofuel production. Under tropical conditions, Arthrospira achieved 84 to 96 percent removal of ammoniacal nitrogen and 72 to 87 percent phosphorus removal in outdoor raceway ponds, and olive oil mill wastewater treated with microalgae yielded 73 percent chemical oxygen demand removal along with complete elimination of phenols, phosphorus and nitrates.

What makes this approach commercially compelling is the sheer value of what the algae produce. Countries including China, Germany, Japan and Taiwan collectively yield roughly 19,000 tonnes of dehydrated microalgal biomass annually, generating a turnover of 5.7 billion US dollars through derived high-value products. The biomass contains lipids, proteins, pigments, carbohydrates, vitamins and minerals that can be converted into biofuels such as biogas, biodiesel, bio-hydrogen, bioethanol and biobutanol through thermochemical and biological routes. Third-generation biofuels from microalgae avoid the food-versus-fuel conflicts of earlier generations, and when combined with co-product extraction, the economics improve substantially. The review notes that pyrolysis of microalgae also yields astaxanthin, carotenoids, phycocyanin, fatty acids, lectins and polysaccharides, creating multiple revenue streams from a single feedstock.

Pigments represent some of the most lucrative products in the microalgal portfolio. Phycocyanin, the brilliant blue water-soluble protein extracted mainly from red algae and cyanobacteria, is projected to reach a global market value of 245.5 million dollars by 2027. Spirulina, or Arthrospira platensis, remains the primary industrial source, supplying powder and aqueous formulations for cosmetics, food and analytical applications. Beyond its role as a natural colorant replacing synthetic dyes with their adverse effects, phycocyanin exhibits immunomodulating, antioxidant, anti-nephrolith and anti-cancer activities, and its fluorescence properties have inspired phycofluor probes for immunodiagnostics and biosensors capable of detecting heavy metals like mercury at low concentrations. Phycoerythrin, a 263-kilodalton phycobiliprotein from Porphyridium species, has been produced in quantity from microalgae grown in slaughterhouse wastewater, demonstrating that even the most challenging effluents can support premium product formation.

Carotenoids form another pillar of the value proposition. Astaxanthin, a naturally occurring keto-carotenoid, boasts antioxidant power approximately 1,000 times greater than vitamin E and ten times greater than other microalgal carotenoids. Its annual market value has surpassed 550 million US dollars, with Haematococcus pluvialis and Chlorella zofingiensis serving as the main producers. Researchers have grown these species in palm oil mill effluent, achieving phycoremediation and astaxanthin production simultaneously, and two-stage LED lighting strategies have further enhanced yields. Fucoxanthin, a xanthophyll from brown algae and diatoms, commands prices between 40,000 and 80,000 US dollars per kilogram for pure material, with a global market estimated at roughly 600 million dollars in 2020. The diatom Phaeodactylum tricornutum, grown in diluted swine wastewater, produced high fucoxanthin yields while removing toxic nutrients, and the Israeli firm Algatechnologies launched the first commercial microalgal fucoxanthin product, Fucovital, in 2018 using closed tubular photobioreactors.

Beyond pigments, the biochemical versatility of wastewater-grown microalgae extends into nutrition and materials science. Under stress conditions, microalgae can accumulate up to 60 percent triacylglycerols, providing viable biodiesel feedstock, with wastewater-derived biodiesel reaching 0.40 to 0.78 tonnes per hectare per year. Polyunsaturated fatty acids such as omega-3, EPA and DHA, produced by species like Nannochloropsis oceanica cultivated in industrial effluents, can replace fish oil in aquaculture feeds. Spirulina strains contain gamma-linolenic acid at levels rivaling the best plant sources, and Arthrospira biomass is roughly 70 percent protein by dry weight with digestibility of 83 to 90 percent. Microalgae also synthesize polyhydroxyalkanoates, biodegradable biopolyesters with thermoplastic and elastomeric qualities that promise alternatives to conventional plastics, and their biomass serves as biofertilizer, with field trials in Indian paddy systems showing doubled chlorophyll and carbohydrate content in algal mats and significantly enriched iron, magnesium and calcium in rice grains.

The review also points to genetic engineering as the next frontier. Advances in CRISPR gene editing and omics technologies have opened unprecedented prospects for creating modified microalgal strains with elevated pigment production and tailored metabolic pathways. Promoters, gene vectors, selection markers and gene editors are now available for rewiring microalgal metabolism, potentially enabling fourth-generation energy feedstocks and enhanced secondary metabolite output. Yet the authors caution that commercialization remains hindered by high cultivation costs, and that most products derive from only a handful of genera. Poor productivity, slow growth rates, lack of robustness and continued reliance on conventional technology explain why only around fifteen strains are cultivated at industrial scale despite tens of thousands of known species. Optimized upstream and downstream processing, combined with symbiotic co-cultivation systems and strategic wastewater pretreatment, will be crucial to closing the gap between laboratory promise and full-scale operation.

The vision that emerges from this synthesis is one of integrated biorefineries where wastewater treatment, carbon dioxide fixation and high-value product generation happen in a single loop. Combining pigment extraction with biogas production from residual biomass, for instance, yields an estimated 5 to 10 percent additional energy recovery while advancing circular economy goals. The authors argue that collaborative efforts among researchers, industries and policymakers will be decisive in scaling microalgae-based wastewater treatment, and that sustained investment in research and development can unlock the full potential of these organisms. If the technical and economic barriers fall, the humble microalga could become a cornerstone of sustainable resource management, simultaneously delivering cleaner water, renewable fuels, nutritious foods, natural colorants and biodegradable materials from streams we currently flush away.

Subject of Research: Microalgae-based wastewater treatment and biorefinery production of high-value products

Article Title: Microalgae cultivation and value-based products from wastewater: insights and applications

Article References: Gupta, R., Mishra, N., Singh, G., Mishra, S., & Lodhiyal, N. (2024). Microalgae cultivation and value-based products from wastewater: insights and applications. Blue Biotechnology, 1(1), Article 20. https://doi.org/10.1186/s44315-024-00019-1

Image Credits: AI Generated

DOI: 10.1186/s44315-024-00019-1

Keywords: microalgae, wastewater treatment, phycoremediation, biorefinery, phycocyanin, astaxanthin, fucoxanthin, biodiesel, circular economy, nutraceuticals, polyhydroxyalkanoates, biofertilizers

The commercial stakes are enormous. The global carotenoid market was valued at 1.44 billion dollars in 2019 and is projected to reach 1.84 billion dollars by 2027, driven by demand for natural antioxidants, pro-vitamin A supplements, and clean-label colorants. Humans cannot synthesize carotenoids themselves, so they must come from diet or supplementation. Beta-carotene, with its two beta-ionone rings, carries full pro-vitamin A activity and supports vision, immune function, and reproduction. Astaxanthin, meanwhile, is a particularly fierce neutralizer of reactive oxygen species, outperforming lutein, lycopene, and beta-carotene in antioxidant assays. These health credentials explain why the pigments command premium prices in nutraceutical and skincare formulations.

Today, most carotenoids come from three routes: chemical synthesis, plant extraction, and microbial fermentation. Chemical synthesis relies on substrates such as acetone, butadiene, and methanol, generating hazardous waste and producing mixtures of stereoisomers, some of which are biologically inactive and face stricter regulatory scrutiny. Plant extraction suffers from low productivity, seasonal variability, and heavy demands on land and water. Fermentation, by contrast, offers year-round production, modest water and nutrient requirements, and the ability to grow microbes on cheap substrates such as lignocellulosic hydrolysates and waste biomass. Companies including DSM Nutritional Products, Cyanotech, AstaReal, Algatech, and Novozymes already use microbial fermentation to produce carotenoids at industrial scale, underscoring that the technology is not merely a laboratory curiosity.

Yeasts are especially attractive hosts because many strains are generally recognized as safe, they grow rapidly in bioreactors, and their genetics and metabolism are exceptionally well characterized. Some yeasts, such as Rhodotorula and Xanthophyllomyces species, naturally produce carotenoids, while workhorse organisms like Saccharomyces cerevisiae and Yarrowia lipolytica do not, but can be engineered to do so. The biosynthetic route runs through the mevalonate pathway: two molecules of acetyl-CoA are condensed to acetoacetyl-CoA, converted through HMG-CoA to mevalonate, and then processed into isopentenyl diphosphate and its isomer dimethylallyl pyrophosphate. These five-carbon building blocks are stitched together into farnesyl pyrophosphate and geranylgeranyl pyrophosphate, the immediate precursors of carotenoids. Phytoene synthase then catalyzes the first colored step, and a cascade of desaturases, cyclases, hydroxylases, and ketolases converts phytoene into lycopene, beta-carotene, zeaxanthin, and ultimately astaxanthin.

Engineering these pathways has produced striking results. Overexpressing the GGS1 gene in Yarrowia lipolytica using CRISPR-Cas9 integration raised beta-carotene titers from 17.1 to 40.4 milligrams per liter, and engineered strains have achieved beta-carotene contents of 4 percent of dry cell weight, several times the concentration found in carrots. Adding extra copies of the ERG13 gene, which encodes HMG-CoA synthase, boosted beta-carotene titers by 259 percent relative to wild type, while duplicating the erg10 gene increased production by 46.9 percent. Feeding hydrophobic substrates such as oleic acid or waste oil helps too, because beta-oxidation of fatty acids raises intracellular acetyl-CoA, the fundamental carbon skeleton from which all carotenoids are built.

Enzyme engineering adds another layer of control. Lycopene cyclase normally suffers from substrate inhibition, diverting flux away from beta-carotene, so researchers screened fifty variants of a bifunctional phytoene synthase/lycopene cyclase and identified a mutant, Y27R, that lost the inhibition entirely. That single change directed carotenoid flux completely toward beta-carotene, yielding an extraordinary 39.5 grams per liter in Yarrowia lipolytica. Directed evolution and adaptive laboratory evolution have also delivered: combining atmospheric and room temperature plasma mutagenesis with hydrogen peroxide-driven selection produced a Saccharomyces cerevisiae strain that reached 404.78 milligrams per liter of astaxanthin in a 5-liter fermenter, the highest reported titer in that organism.

Because carotenoids are hydrophobic molecules stored in lipid bodies, lipid engineering has become a powerful lever. Deleting the POX1 through POX6 beta-oxidation genes and the GUT2 glycerol-3-phosphate dehydrogenase gene in Yarrowia lipolytica enlarged intracellular lipid droplets, expanding storage capacity and pushing lycopene yields to 16 milligrams per gram of dry cell weight in fed-batch culture. Overexpressing lipid synthesis genes such as PAH1, DGA1, and a mutated ACC1 in S. cerevisiae raised both triacylglycerol and lycopene accumulation, confirming a direct correlation between fat storage and pigment yield. Even cell morphology matters: reverting filamentous Yarrowia growth back to yeast form by deleting the CLA4 and MHY1 genes increased beta-carotene production to 7.6 grams per liter, while expanding the endoplasmic reticulum through INO2 overexpression boosted terpene synthesis dramatically.

Yet even the best engineered strains hit ceilings, and this is where metabolomics enters the story. Metabolomic profiling, using techniques such as gas chromatography-mass spectrometry, HPLC-MS, and UPLC-MS/MS, measures the actual chemical state of a cell, capturing the end products of gene expression and regulation more faithfully than transcriptomic or proteomic data. In one study, comparative metabolomics of a recombinant beta-carotene-producing S. cerevisiae strain revealed significant depletion of amino acid, carbohydrate, and TCA cycle intermediates, showing that carotenoid synthesis drains core metabolism. Supplementing the culture with acetate during exponential growth restored intracellular pools and raised beta-carotene production by 39.3 percent. In Rhodosporidium toruloides, time-dependent metabolomics of three strains grown on glycerol showed that the best producer, CBS 5490, achieved 28.5 milligrams per liter by downregulating TCA cycle and amino acid metabolism, effectively redirecting energy and flux toward carotenoid and fatty acid synthesis.

Metabolomics has also illuminated how environmental conditions shape production. In Rhodosporidiobolus colostri, lowering the cultivation temperature to 16 degrees Celsius increased total carotenoids from 17.1 to 29.0 milligrams per liter, and integrated transcriptomic and metabolomic analysis suggested that reduced TCA cycle flux freed acetyl-CoA for beta-carotene and torulene biosynthesis. In engineered lycopene-producing Yarrowia lipolytica, metabolomic comparison with the wild type revealed that lycopene accumulation reshaped fructose and mannose metabolism, the citrate cycle, and glycerophospholipid metabolism, and pointed to shortages of glycerol backbone intermediates rather than fatty acids as the limiting factor for lipid storage. Such insights convert blind strain engineering into rational design, telling researchers precisely which genes to tune and which metabolites to replenish.

The review’s authors argue that cost remains the decisive barrier to commercialization. Expensive carbon sources like glucose inflate fermentation costs, so future work will focus on agricultural byproducts, lignocellulosic biomass, and industrial waste streams as feedstocks, alongside stress-tolerant strains that withstand high temperature, low pH, and high oxygen. Downstream innovations such as enzyme-based cell lysis, membrane extraction, and supercritical CO2 processing promise to cut solvent use and recovery costs. Engineering transporters to export carotenoids could eliminate the need for cell disruption altogether, and hybrid pathways combining the yeast mevalonate route with the bacterial MEP pathway could balance precursor supply and ATP demand. With life cycle assessments and regulatory frameworks still to be established, yeast-derived carotenoids stand at the threshold of replacing synthetic pigments, offering a vision of color and nutrition brewed sustainably in stainless steel tanks rather than extracted from fields or synthesized in chemical plants.

Subject of Research: Metabolomics-guided metabolic engineering of yeasts for cost-effective carotenoid biosynthesis

Article Title: Unlocking yeast’s palette: leveraging metabolomics and gene editing approaches for cost effective carotenoid production

Article References: Arora, N., & Pritam, P. (2025). Unlocking yeast’s palette: leveraging metabolomics and gene editing approaches for cost effective carotenoid production. Blue Biotechnology, 2(1), Article 5. https://doi.org/10.1186/s44315-025-00028-8

Image Credits: AI Generated

DOI: 10.1186/s44315-025-00028-8

Keywords: carotenoids, yeast, metabolomics, CRISPR-Cas9, metabolic engineering, synthetic biology, beta-carotene, astaxanthin, lycopene, Yarrowia lipolytica, Saccharomyces cerevisiae, fermentation

Nannochloropsis oceanica occupies a special place among photosynthetic chassis organisms. It is a haploid alga whose nuclear genome has been fully sequenced and extensively annotated, and it naturally produces high levels of triacylglycerol rich in eicosapentaenoic acid, a high-value omega-3 long-chain polyunsaturated fatty acid increasingly sought after as a food resource for human consumption. Genetic tools for gene overexpression, suppression, subcellular localization and genome editing have been developed for the species over the past decade, and transgene expression has proven stable. Yet most published engineering efforts have introduced no more than three transgenes at a time, and the plasmid construction behind them remained laborious. That bottleneck is precisely what a MoClo system is designed to eliminate.

MoClo is built on the Golden Gate cloning technique, which exploits Type IIS restriction enzymes that recognize asymmetric DNA sequences and cut outside their recognition sites, generating defined overhangs. Because these overhangs can be assigned to specific positions in a genetic construct, multiple DNA fragments can be ligated together seamlessly in a single reaction tube, with no scar sequences left behind. The approach, first formalized in 2011, has since spawned tailored toolkits for bacteria such as Escherichia coli, the yeast Saccharomyces cerevisiae, the land plant Nicotiana benthamiana, and microalgae including Synechocystis, Synechococcus elongatus and Chlamydomonas reinhardtii. The new work extends this lineage to the stramenopile algae, adopting the syntax proposed by the plant synthetic biology community so that parts can, in principle, be exchanged across platforms.

The architecture of the Nannochloropsis toolkit follows the familiar three-level hierarchy of MoClo systems. Level 0 vectors carry individual genetic parts flanked by eight distinct fusion sites; these parts can be shuttled into level 1 vectors to build single transcriptional modules, and those modules can then be stacked into level 2 vectors carrying multiple expression cassettes. The 91 parts represent 39 unique genetic elements distributed across the standard framework and fall into clear functional categories: 12 promoters placed at three different positions, five terminators plus one polygenic terminator, five selectable markers, six signal peptides with two position options each, four reporter genes with five position options, five affinity tags, and one 2A peptide for expressing fused proteins from a single open reading frame.

Functional validation began with the selectable markers, which determine how efficiently transformed cells can be recovered. The team assembled four vectors pairing either the zeocin-resistance gene Ble from Streptoalloteichus hindustanus or the hygromycin B-resistance gene Hyg from Streptomyces hygroscopicus with two different promoter-terminator combinations: the RIBI promoter paired with the HS terminator, both of Nannochloropsis origin, and the VCP2 promoter paired with the FCPA terminator from the diatom Phaeodactylum tricornutum. Counting antibiotic-resistant colonies after electroporation revealed that the RIBI-HS combination outperformed VCP2-FCPA regardless of which marker was used, and reverse transcription quantitative PCR confirmed that the winning pair also drove higher transcription of the marker genes. The lesson, the authors note, is that promoter activity in this alga depends strongly on the terminator it is paired with, a phenomenon also documented in Chlamydomonas.

To quantify expression more precisely, the researchers turned to NanoLuciferase, a small and highly sensitive reporter. They built six level 2 vectors in which the Nluc gene was driven by three promoters, RIBI, VCP2 and the beta-tubulin promoter TUB, each paired with either the HS or FCPA terminator. Luminescence from transformed cultures correlated linearly with cell density, allowing quantitative comparison, and the spread between constructs was striking: otherwise identical constructs differing only in terminator produced dramatically different light output. The best-performing combination, pairing the TUB promoter with the FCPA terminator, yielded the highest luminescence, reinforcing the conclusion that promoter-terminator compatibility must be evaluated as a unit rather than assuming promoter strength is an intrinsic property.

Visualization tools received equally systematic treatment. The toolkit’s fluorescent protein set includes enhanced green fluorescent protein, enhanced yellow fluorescent protein and StayGold, a highly photostable and bright GFP variant that had never before been evaluated in Nannochloropsis. All three produced strong cytosolic fluorescence when expressed alone. The team then fused transit peptides to direct the reporters to specific compartments: chloroplast transit peptides from the glycine cleavage system L protein and from the violaxanthin/chlorophyll a-binding protein steered eGFP into the chloroplast, while the simian virus 40 nuclear localization sequence confined eYFP to a single nuclear spot. Crucially, dual-cassette constructs allowed two reporters to be targeted simultaneously, one to the chloroplast and one to the nucleus, demonstrating that the system supports co-localization studies within a single transformant. Five epitope tags, HA, 6xHis, Flag, Myc and StrepII, were also validated by immunoblotting, with the HA tag producing the strongest signal and four of the five tags being demonstrated in this organism for the first time.

The demonstration that ties the toolkit together is metabolic: the modular assembly of keto-carotenoid biosynthetic pathways. Canthaxanthin and astaxanthin are red-pigmented carotenoids with powerful antioxidant properties and established markets in food, feed and nutraceuticals. The researchers assembled a beta-carotene ketolase from Chlamydomonas, targeted to the chloroplast, to produce canthaxanthin, and a two-enzyme module combining that ketolase with a beta-carotene hydroxylase from Haematococcus lacustris to produce astaxanthin. Transformants turned visibly orange, accumulating 4.5 milligrams of canthaxanthin or 2.8 milligrams of astaxanthin per gram of dry weight, comparable to yields previously achieved with traditional cloning. Interestingly, the engineered strains accumulated more keto-carotenoid under normal light than under high light, the opposite of the stress-induced production seen in natural producers like Haematococcus, likely because high light depletes the beta-carotene precursor pool in Nannochloropsis. Canthaxanthin was even detected in isolated thylakoid membranes, at 4.4 moles per 100 moles of chlorophyll a, and transcriptomic analysis showed that the engineered accumulation perturbed endogenous carotenoid gene expression only mildly, with fold changes below 1.5.

The practical implications extend well beyond pigments. Because assembly is modular, the authors estimate that researchers can now design and construct complex constructs carrying up to six distinct genes in a single level 2 vector within days rather than weeks, and the availability of multiple selectable markers means more than one level 2 vector can be introduced at once, theoretically allowing over ten genes to be stacked. The toolkit also proved portable: introducing the canthaxanthin module into Nannochloropsis gaditana, a close industrial relative, likewise yielded substantial canthaxanthin. Combined with existing CRISPR-Cas genome editing systems and high-throughput microfluidic screening, the toolkit positions Nannochloropsis as a genuine sunlight-driven chassis for carbon-neutral biomanufacturing, in which captured CO2 becomes feedstock for lipids, carotenoids and other high-value biochemicals grown in seawater rather than on arable land.

There remain honest limits. Astaxanthin yields in the engineered Nannochloropsis still fall far short of the roughly four percent of cell dry weight that stressed Haematococcus cultures can reach, and the authors point to strengthening the plastidial MEP pathway and beta-carotene supply as the logical next engineering targets. But the structural obstacle, the absence of a fast, standardized, expandable assembly system, has now been removed. With 91 validated parts, a shared syntax compatible with the broader plant and algal synthetic biology community, and demonstrated performance across two Nannochloropsis species, the toolkit converts what was once a craft-based cloning exercise into an engineering discipline, opening the door to rapid design-build-test cycles for anyone hoping to turn these tiny marine cells into photosynthetic factories.

Subject of Research: Development of a modular cloning toolkit for metabolic engineering of the microalga Nannochloropsis

Article Title: A modular synthetic biology toolkit unlocks metabolic engineering of the industrially relevant alga Nannochloropsis

Article References: Guo, Y., Li, Z., Wang, H., Zheng, J., Liang, Z., Sun, H., Zhou, W., & Liu, J. (2026). A modular synthetic biology toolkit unlocks metabolic engineering of the industrially relevant alga Nannochloropsis. Advanced Biotechnology, 4(1), Article 2. https://doi.org/10.1007/s44307-026-00096-w

Image Credits: AI Generated

DOI: 10.1007/s44307-026-00096-w

Keywords: synthetic biology, Nannochloropsis, MoClo, Golden Gate cloning, metabolic engineering, microalgae, canthaxanthin, astaxanthin, carotenoid biosynthesis, CO2 valorization, genetic toolkit, algal biotechnology

The research team, led by Danhong Ge, YangYang Luo, Ruyu Zhang, Xuechao Hu, and Lujing Ren, set out to answer a deceptively simple question: what happens when you expose a microbe that normally grows in the dark to sustained light stress? Schizochytrium sp. HX-308, the strain used in the study, was isolated from seawater and deposited in the China Center for Type Culture Collection. In industrial settings it is typically fermented in large, dark vessels where it converts glucose into a lipid-rich biomass. Light, in this context, is usually treated as an irrelevance or even a nuisance. The new study suggests that assumption deserves a second look, because light turns out to be a powerful abiotic stress factor that reprograms the cell’s entire metabolic priorities.

The researchers divided the fermentation process into three distinct phases: a cell growth stage from zero to forty-eight hours, a lipid accumulation stage from forty-eight to ninety-six hours, and a lipid turnover stage from ninety-six to one hundred forty-four hours, when the cells begin consuming their own stored fat reserves. Under normal dark conditions, the culture reached a maximum cell dry weight of 50.5 grams per liter at seventy-two hours. When the flasks were illuminated with an array of LED strips delivering a total luminous flux of 18,311.4 lumens, growth slowed noticeably. Glucose consumption was delayed, the fermentation cycle stretched from seventy-two to ninety-six hours, and the peak biomass fell to 41.3 grams per liter, a reduction of 18.21 percent compared with the dark-grown control.

Microscopy revealed that the light-exposed cells were visibly different from their dark-grown counterparts. They grew larger in diameter, became more dispersed and independent in their morphology, and accumulated more prominent lipid droplets as the fermentation progressed. Using propidium iodide staining under a confocal fluorescence microscope, the team showed that cell membrane damage was consistently higher under light stress, peaking at ninety-six hours, precisely when the lipid turnover phase begins. The researchers hypothesize that the enlarged cell diameter is an adaptive response, allowing the organism to meet the elevated energy and material demands imposed by the stressful environment. Similar light-induced changes in cell size have been documented in diatoms such as Ditylum brightwellii, suggesting this may be a widespread strategy among marine microbes.

The real surprise came when the team measured what the cells were actually producing. Although the light-stressed cultures grew more slowly, their final lipid yield reached 8.45 grams per liter, a striking 39.67 percent higher than the 6.05 grams per liter measured in the control after the turnover phase had run its course. The delayed glucose consumption appears to slow the onset of lipid turnover, effectively extending the window during which the cells hold onto their oil. In other words, the stress that cost the microbe some of its growth paid off handsomely in the currency that industry actually cares about: stored lipid that survives to the end of the fermentation.

The composition of that lipid changed too, and in commercially interesting directions. Saturated fatty acids, particularly myristic acid (C14:0) and palmitic acid (C16:0), were 1.49 times more abundant in the light-treated group, reaching 4.97 percent and 15.86 percent of the total fatty acid pool respectively. Saturated fats of this kind are the raw material for neutral lipid formation and have their own market in oleochemical applications. Meanwhile, the polyunsaturated fatty acids docosapentaenoic acid and DHA declined modestly, from 24.74 percent and 59.14 percent in the control to 20.59 percent and 56.28 percent under light. But eicosapentaenoic acid, or EPA, an omega-3 fatty acid with anti-inflammatory applications and a notoriously difficult production process, jumped from 2.14 percent to 8.30 percent of total fatty acids, a 3.88-fold increase that caught the researchers’ attention.

Beyond the fatty acids, light stress proved to be a potent trigger for two of the microbe’s most valuable secondary metabolites. Squalene, a terpenoid used in cosmetics, vaccines, and pharmaceutical formulations, peaked at 67.46 milligrams per liter at seventy-two hours under light stress, compared with 55.67 milligrams per liter at forty-eight hours in the dark, and the light-stressed cultures sustained higher squalene levels through the later stages of fermentation, ending 21.17 percent above the control. Beta-carotene followed a similar pattern, peaking at roughly 7,184 micrograms per liter at ninety-six hours under light versus 5,368 micrograms per liter at seventy-two hours in the dark. By the end of fermentation, the light-stressed cultures contained 5,675 micrograms per liter of beta-carotene, 4.75 times the control level. Astaxanthin, a premium carotenoid synthesized downstream of beta-carotene, rose continuously throughout the light-stressed fermentation, finishing nearly 2,081 micrograms per liter, 11.39 percent above the control, and its accumulation only accelerated after beta-carotene had peaked, consistent with beta-carotene serving as a metabolic precursor.

To understand why light produces these effects, the team measured intracellular reactive oxygen species and performed a full transcriptomic analysis using Illumina RNA sequencing. Light stress elevated oxidative pressure inside the cells, but the light-stressed cultures actually showed lower peak ROS levels than the controls, indicating that the organism mounts a robust antioxidant defense. The transcriptome told the molecular story. A core set of 226 differentially expressed genes was shared across all light-versus-dark comparisons, while the 144-hour comparison alone revealed 788 unique light-responsive genes. At seventy-two hours, light stress predominantly suppressed metabolic genes, an acute stress response; by 144 hours, the pattern flipped to widespread upregulation, signaling a transition to long-term metabolic reprogramming. Gene ontology analysis showed marked enrichment of genes involved in stimulus response, antioxidant activity, and transporter activity under light, while genes for lipid biosynthesis and antioxidant processes became dominant at the later time point.

The pathway-level details are particularly revealing. In the mevalonate pathway, which supplies the building blocks for isoprenoids such as squalene, the enzyme isopentenyl diphosphate isomerase was significantly upregulated under light, especially at 144 hours, along with farnesyl diphosphate synthase and squalene synthase, the enzymes that assemble farnesyl diphosphate into squalene itself. Fatty acid metabolism showed a dual pattern: acetyl-CoA carboxylase and fatty acid synthase were upregulated, driving carbon toward palmitic acid, while a key beta-oxidation gene was downregulated, meaning the cells burned less of the fat they stored. Intriguingly, glycolysis genes were suppressed, suggesting the microbe rerouted carbon flux away from rapid energy production and toward lipid and terpenoid biosynthesis, a strategy that mirrors engineered lipid-boosting interventions in other microalgae. The upregulated polyketide synthase genes hint at the channeling of resources toward EPA production, which supports membrane fluidity under stress.

For the biotechnology industry, the implications are considerable. Light is an inexpensive, non-invasive, and precisely controllable stimulus compared with chemical additives or genetic engineering, and this study demonstrates that it can simultaneously raise lipid yield, enrich EPA, and boost squalene and carotenoid production in a single fermentation run. The trade-off, a longer fermentation cycle and lower biomass, is a real cost, but the researchers argue that the metabolic insights gained here, particularly the coordinated upregulation of the mevalonate pathway and the suppression of fatty acid degradation, could guide further optimization, whether through tuned light regimens, light combined with other stressors, or targeted engineering of the genes identified in the transcriptome. As demand for omega-3 oils and natural antioxidants continues to climb, the idea that a well-placed bank of LED strips could coax more value out of every liter of fermentation broth is an appealingly simple proposition, and one that this marine microbe appears ready to deliver on.

Subject of Research: Effect of light stress on lipid, fatty acid, squalene, and carotenoid biosynthesis in the marine protist Schizochytrium sp.

Article Title: Effect of light stress on the production of lipid compounds by Schizochytrium sp. and its underlying mechanism

Article References: Ge, D., Luo, Y., Zhang, R., Hu, X., & Ren, L. (2025). Effect of light stress on the production of lipid compounds by Schizochytrium sp. and its underlying mechanism. Blue Biotechnology, 2(1), Article 8. https://doi.org/10.1186/s44315-025-00029-7

Image Credits: AI Generated

DOI: 10.1186/s44315-025-00029-7

Keywords: Schizochytrium, light stress, lipid biosynthesis, EPA, DHA, squalene, beta-carotene, astaxanthin, reactive oxygen species, transcriptomics, mevalonate pathway, marine biotechnology

The study addresses a persistent challenge in ornamental aquaculture. Fish cannot synthesize carotenoids, the family of pigments responsible for the reds, oranges, and yellows that make reef fish so commercially desirable, so captive animals depend entirely on dietary supply. In the wild, clownfish accumulate carotenoids through their prey; in captivity, formulated feeds must deliver them. Without adequate supplementation, captive-bred specimens often fade to paler versions of their wild counterparts, eroding their market value and, by extension, the economic case for farming rather than wild-capture, which remains a major pressure on reef ecosystems.

Astaxanthin, the ketocarotenoid that colors salmon flesh and flamingo plumage, is widely regarded as the most effective pigmenting compound for fish. It occurs naturally in microalgae, bacteria, and crustaceans, with Haematococcus pluvialis serving as the leading commercial source of the natural form. Synthetic astaxanthin, produced by chemical synthesis, dominates the salmon-feed market because it is cheaper. Beyond coloration, astaxanthin participates in a suite of biological functions: it protects tissues against photooxidation, prevents oxidation of polyunsaturated fatty acids, supports immune responses, and influences reproductive behavior and output. That breadth of activity makes the choice between natural and synthetic sources consequential for animal welfare as well as aesthetics.

The Brazilian team, led by Higor Hoffmann and including colleagues from the university’s Laboratory of Fish and Marine Ornamentals and Laboratory of Algae Cultivation, set out to compare the two sources head to head at low inclusion levels. They randomly assigned 180 five-month-old juvenile clownfish, averaging 0.70 grams in weight and 2.89 centimeters in length, among nine 90-liter blue fiberglass tanks, twenty fish per tank, with three tanks per treatment. The three diets were a commercial control feed, the same feed spiked with synthetic astaxanthin (Carophyll Pink 10%), and feed supplemented with natural astaxanthin from H. pluvialis (Naturose, containing 1.5% astaxanthin). Because the natural product is far less concentrated, the researchers added 1.2 grams per kilogram of the algal product versus 0.18 grams per kilogram of the synthetic one, both targeting an intended dietary astaxanthin concentration of 18 milligrams per kilogram. The pigment was first dissolved in soybean oil and sprayed onto the feed, which was then dried under forced ventilation and stored frozen.

Water quality was tightly controlled throughout the trial in a recirculating system supplied with ocean water from Mozambique Beach in Florianópolis, Brazil, filtered mechanically and biologically, sterilized with ultraviolet light, and conditioned with a foam fractionator. Salinity held at 34.15 parts per thousand, temperature at 26.5 degrees Celsius, dissolved oxygen at 7.13 milligrams per liter, and pH at 8.14, with ammonia and nitrite kept near 0.10 milligrams per liter. Fish were fed twice daily at 4% of tank biomass, and biometric measurements were taken on days 0, 15, 30, 45, and 60 under clove-oil anesthesia. Survival was a perfect 100% in every treatment, and overall growth performance did not differ significantly among diets by the end of the trial, although the natural-astaxanthin group did show significantly greater weight and length than the control at the day-30 measurement.

The real story unfolded in the color data. To quantify pigmentation objectively, the team photographed anesthetized fish individually against a white background under standardized lighting, four 18-watt 6500-kelvin compact fluorescent lamps in a closed room, with an 18% gray card for white-balance correction and yellow and red reference cards for calibration. They then analyzed five body regions, head, dorsal, ventral, pectoral fin, and caudal fin, plus the whole body, converting RGB values from the digital images into the HSB color model, which decomposes color into hue, saturation, and brightness in a way that approximates human perception. Hue, measured in degrees, indicates the authenticity of the color, with values near 0 or 360 degrees corresponding to red; saturation reflects color intensity relative to gray; and brightness runs from black to white. Because saturation and brightness are expressed as percentages, the researchers converted them to radians for parametric analysis.

The hue results were decisive. Fish on the natural-astaxanthin diet showed significant hue reductions, meaning a shift toward deeper red, in all five body regions and across the whole body, with decreases ranging from 25 to 29 degrees and a final whole-body value of 24.7 degrees. The ventral region responded fastest, with significant reddening appearing by day 30, and the head region reached its lowest recorded hue, 23.3 degrees, by day 45. Synthetic astaxanthin produced significant hue shifts in fewer regions and generally later in the trial; in the dorsal region, for example, a significant change appeared on day 45 but reverted to near-initial values by day 60. The authors attribute the early ventral response to the fat-soluble nature of natural astaxanthin and the higher lipid content of the ventral region, which favors pigment accumulation in the chromatophores there.

Saturation told a complementary story. By day 60, fish on the natural-astaxanthin diet displayed higher saturation values, between 81% and 93%, across nearly all skin regions, indicating more intense coloration with less dilution by gray. Notably, the natural group began fluctuating in saturation as early as day 15, while the other groups did not respond until day 45, and despite an initially lower value, the natural group finished with the highest saturation overall. Brightness declined significantly in the ventral and caudal fin regions and for the whole body in the natural group from day 45 onward, a pattern consistent with deeper, richer pigmentation. Chemical verification by HPLC-MS-MS confirmed that astaxanthin was successfully incorporated into the supplemented feeds, with measured concentrations of 16.53 milligrams per kilogram in the synthetic diet and 14.82 milligrams per kilogram in the natural diet, against 10.74 milligrams per kilogram in the control, a baseline presence the authors attribute to salmon meal in the commercial feed.

The findings align with earlier work showing that algal astaxanthin enhances clownfish pigmentation. Lee and colleagues previously reported marked reddening of A. ocellaris by the sixth week of supplementation with H. pluvialis extract at 200 and 400 milligrams per kilogram, considerably higher doses than those used here. Other studies have explored plant-derived alternatives, including carotenoids from gac fruit and bell pepper at 250 milligrams per kilogram, which improved growth and feed efficiency, and blends of paprika, turmeric, and chlorophyll oleoresins that boosted growth metrics. Researchers in Vietnam found that sweet potato and Enteromorpha carotenoids raised skin redness values above control levels. The Brazilian trial is distinctive in demonstrating a clear natural-versus-synthetic advantage at a comparatively modest inclusion level, suggesting that the esterified, protein-associated form of astaxanthin in algal biomass may be more bioavailable to clownfish than the free synthetic compound.

For the ornamental fish industry, the implications are practical and potentially transformative. Clownfish are among the most successfully captive-bred marine ornamentals, and the trade’s sustainability depends on farmed specimens that match or exceed the vibrancy of wild-caught fish. Because coloration is directly tied to market value, a feeding strategy that delivers redder, more saturated fish within a 60-day production cycle, using a renewable microalgal ingredient, strengthens both the economics of hatchery production and the conservation case against reef collection. The authors conclude that H. pluvialis-derived astaxanthin is a valuable tool for aquaculture, with the caveat that optimal dosage and timing still warrant refinement, since previous studies have reported inconsistent requirements. What is already clear is that when it comes to painting Nemo, the alga does it better.

Subject of Research: Effects of natural versus synthetic astaxanthin supplementation on the coloration, growth, and survival of juvenile clownfish Amphiprion ocellaris

Article Title: Natural or synthetic carotenoid: impacts of Haematococcus pluvialis-derived astaxanthin and synthetic astaxanthin on the diet of clownfish Amphiprion ocellaris

Article References: Hoffmann, H., Ozório, R. Á., Lopes, R. G., Owatari, M. S., Tsuzuki, M. Y., & Derner, R. B. (2025). Natural or synthetic carotenoid: impacts of Haematococcus pluvialis-derived astaxanthin and synthetic astaxanthin on the diet of clownfish Amphiprion ocellaris. Blue Biotechnology, 2(1), Article 17. https://doi.org/10.1186/s44315-025-00041-x

Image Credits: AI Generated

DOI: 10.1186/s44315-025-00041-x

Keywords: astaxanthin, Haematococcus pluvialis, clownfish, Amphiprion ocellaris, carotenoids, ornamental aquaculture, fish pigmentation, microalgae, HSB color model, aquaculture nutrition, marine ornamental fish trade, synthetic pigment