Orange carotenoid proteins: structural understanding of evolution and function.

Cyanobacteria uniquely contain a primitive water-soluble carotenoprotein, the orange carotenoid protein (OCP). Nearly all extant cyanobacterial genomes contain genes for the OCP or its homologs, implying an evolutionary constraint for cyanobacteria to conserve its function. Genes encoding the OCP and its two constituent structural domains, the N-terminal domain, helical carotenoid proteins (HCPs), and its C-terminal domain, are found in the most basal lineages of extant cyanobacteria. These three carotenoproteins exemplify the importance of the protein for carotenoid properties, including protein dynamics, in response to environmental changes in facilitating a photoresponse and energy quenching. Here, we review new structural insights for these carotenoproteins and situate the role of the protein in what is currently understood about their functions.

Carotenoid cleavage enzymes evolved convergently to generate the visual chromophore.

The retinal light response in animals originates from the photoisomerization of an opsin-coupled 11-cis-retinaldehyde chromophore. This visual chromophore is enzymatically produced through the action of carotenoid cleavage dioxygenases. Vertebrates require two carotenoid cleavage dioxygenases, ß-carotene oxygenase 1 and retinal pigment epithelium 65 (RPE65), to form 11-cis-retinaldehyde from carotenoid substrates, whereas invertebrates such as insects use a single enzyme known as Neither Inactivation Nor Afterpotential B (NinaB). RPE65 and NinaB couple trans-cis isomerization with hydrolysis and oxygenation, respectively, but the mechanistic relationship of their isomerase activities remains unknown. Here we report the structure of NinaB, revealing details of its active site architecture and mode of membrane binding. Structure-guided mutagenesis studies identify a residue cluster deep within the NinaB substrate-binding cleft that controls its isomerization activity. Our data demonstrate that isomerization activity is mediated by distinct active site regions in NinaB and RPE65-an evolutionary convergence that deepens our understanding of visual system diversity.

The Orange Carotenoid Protein Triggers Cyanobacterial Photoprotection by Quenching Bilins via a Structural Switch of Its Carotenoid.

Cyanobacteria were the first microorganisms that released oxygen into the atmosphere billions of years ago. To do it safely under intense sunlight, they developed strategies that prevent photooxidation in the photosynthetic membrane, by regulating the light-harvesting activity of their antenna complexes-the phycobilisomes-via the orange-carotenoid protein (OCP). This water-soluble protein interacts with the phycobilisomes and triggers nonphotochemical quenching (NPQ), a mechanism that safely dissipates overexcitation in the membrane. To date, the mechanism of action of OCP in performing NPQ is unknown. In this work, we performed ultrafast spectroscopy on a minimal NPQ system composed of the active domain of OCP bound to the phycobilisome core. The use of this system allowed us to disentangle the signal of the carotenoid from that of the bilins. Our results demonstrate that the binding to the phycobilisomes modifies the structure of the ketocarotenoid associated with OCP. We show that this molecular switch activates NPQ, by enabling excitation-energy transfer from the antenna pigments to the ketocarotenoid.

Spectral Tuning and Excitation-Energy Transfer by Unique Carotenoids in Diatom Light-Harvesting Antenna.

The light-harvesting antennae of diatoms and spinach are composed of similar chromophores; however, they exhibit different absorption wavelengths. Recent advances in cryoelectron microscopy have revealed that the diatom light-harvesting antenna fucoxanthin chlorophyll a/c-binding protein (FCPII) forms a tetramer and differs from the spinach antenna in terms of the number of protomers; however, the detailed molecular mechanism remains elusive. Herein, we report the physicochemical factors contributing to the characteristic light absorption of the diatom light-harvesting antenna based on spectral calculations using an exciton model. Spectral analysis reveals the significant contribution of unique fucoxanthin molecules (fucoxanthin-S) in FCPII to the diatom-specific spectrum, and further analysis determines their essential role in excitation-energy transfer to chlorophyll. It was revealed that the specificity of these fucoxanthin-S molecules is caused by the proximity between protomers associated with the tetramerization of FCPII. The findings of this study demonstrate that diatoms employ fucoxanthin-S to harvest energy under the ocean in the absence of long-wavelength sunlight and can provide significant information about the survival strategies of photosynthetic organisms to adjust to their living environment.

Optimization, characterization and biosafety of carotenoids produced from whey using Micrococcus luteus.

This study aimed to optimize the production of carotenoid pigments from Micrococcus luteus (ATCC 9341) through the statistical screening of media components and the characterization of antimicrobial, antioxidant, cytogenetic and cytotoxic activities. A BOX-Behnken design was used to assess the effects of whey concentration, inoculum size, pH, temperature, and agitation speed on carotenoid yield. The optimum combination increased production to 2.19 g/L, with a productivity of 0.045 g L-1 h-1 and a productivity yield of 0.644 g/g, as confirmed by an observed carotene production of 2.19 g/L. The final response surface model fitting the data had an R2 of 0.9461. High-performance liquid chromatography (HPLC) analysis identified 12 carotenoid pigment compounds produced by M. luteus. The extracts displayed moderate antimicrobial efficacy against Gram-positive bacteria such as Bacillus cereus (ATCC 11778), Staphylococcus aureus (ATCC 6538), and E. faecalis (ATCC 19433), with inhibition zone diameters (IZD) of 29.0, 14.0, and 37.0 mm, respectively, at 1000 µg/mL. However, its effectiveness against Gram-negative bacteria is limited. In comparison, tetracycline exhibited greater antimicrobial potency. The IC50 value of carotenoids was used to indicate the antioxidant activity. IC50 value from the DPPH assay was 152.80 mg/100mL. An IC50 cytotoxicity value greater than 300 µg/mL was found against normal mouse liver cells, with over 68% cell viability even at 300 µg/mL, indicating low toxicity. Histological structure studies revealed normal myocardial muscle tissue, lung tissue, and kidney tissue sections, whereas liver tissue sections revealed ballooning degeneration of hepatocytes and disorganization of hepatic cords. Cytogenetic parameters revealed that the carotene treatment group had a mitotic index (70%) lower than that of the control but higher than that of the positive control, mitomycin, and did not substantially increase numerical (1.2%) or structural aberrations compared with those of the control, suggesting a lack of genotoxic effects under the experimental conditions. In conclusion, optimized culture conditions enhanced carotenoid yields from M. luteus, and the extracts displayed promising bioactivity as moderate antibiotics against certain gram-positive bacteria and as antioxidants. The high IC50 values demonstrate biosafety. Overall, this bioprocess for enhanced carotenoid production coupled with bioactivity profiling and low cytotoxicity support the application of M. luteus carotenoids.

Organization of Carotenoid Aggregates in Membranes Studied Selectively using Resonance Raman Optical Activity.

In living organisms, carotenoids are incorporated in biomembranes, remarkably modulating their mechanical characteristics, fluidity, and permeability. Significant resonance enhancement of Raman optical activity (ROA) signals of carotenoid chiral aggregates makes resonance ROA (RROA), a highly selective tool to study exclusively carotenoid assemblies in model membranes. Hence, RROA is combined with electronic circular dichroism (ECD), dynamic light scattering (DLS), molecular dynamics, and quantum-chemical calculations to shed new light on the carotenoid aggregation in dipalmitoylphosphatidylcholine (DPPC) liposomes. Using representative members of the carotenoid family: apolar α-carotene and more polar fucoxanthin and zeaxanthin, the authors demonstrate that the stability of carotenoid aggregates is directly linked with their orientation in membranes and the monomer structures inside the assemblies. In particular, polyene chain distortion of α-carotene molecules is an important feature of J-aggregates that show increased orientational freedom and stability inside liposomes compared to H-assemblies of more polar xanthophylls. In light of these results, RROA emerges as a new tool to study active compounds and drugs embedded in membranes.

Photogeneration and quenching of singlet molecular oxygen by bacterial C40 carotenoids with long chain of conjugated double bonds.

Measurement of photosensitized luminescence of singlet oxygen has been applied to studies of singlet oxygen generation and quenching by C40 carotenoids (neurosporene, lycopene, rhodopin, and spirilloxanthin) with long chain of conjugated double bonds (CDB) using hexafluorobenzene as a solvent. It has been found that neurosporene, lycopene, and rhodopin are capable of the low efficient singlet oxygen generation in aerated solutions upon photoexcitation in the spectral region of their main absorption maxima. The quantum yield of this process was estimated to be (1.5-3.0) × 10-2. This value is near the singlet oxygen yields in solutions of ζ-carotene (7 CDB) and phytoene (3 CDB) and many-fold smaller than in solutions of phytofluene (5 CDB) (Ashikhmin et al. Biochemistry (Mosc) 85:773-780, https://doi.org/10.1134/S0006297920070056 , 2020, Biochemistry (Mosc) 87:1169-1178, 2022, https://doi.org/10.1134/S00062979221001082022 ). Photogeneration of singlet oxygen was not observed in spirilloxanthin solutions. A correlation was found between the singlet oxygen yields and the quantum yields and lifetimes of the fluorescence of the carotenoid molecules. All carotenoids were shown to be strong physical quenchers of singlet oxygen. The rate constants of 1O2 quenching by the carotenoids with long chain of CDB (9-13) were close to the rate constant of the diffusion-limited reactions ≈1010 M-1 s-1, being many-fold greater than the rate constants of 1O2 quenching by the carotenoids with the short chain of CDB (3-7) phytoene, phytofluene, and ζ-carotene studied in prior papers of our group (Ashikhmin et al. 2020, 2022). To our knowledge, the quenching rate constants of rhodopin and spirilloxanthin have been obtained in this paper for the first time. The mechanisms of 1O2 photogeneration by carotenoids in solution and in the LH2 complexes of photosynthetic cells, as well as the efficiencies of their protective action are discussed.

Apo-12'-capsorubinal exhibits anti-inflammatory effects and activates nuclear factor erythroid 2-related factor 2 in RAW264.7 macrophages.

Apocarotenoids have short carbon chain structures cleaved at a polyene-conjugated double bond. They can be biosynthesized in plants and microorganisms. Animals ingest carotenoids through food and then metabolize them into apocarotenoids. Although several apocarotenoids have been identified in the body, their precise health functions are still poorly understood. This study investigated the anti-inflammatory activities of apo-12'-capsorubinal in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. It was confirmed that apo-12'-capsorubinal was not cytotoxic to the macrophages at the concentrations tested. Apo-12'-capsorubinal treatment led to a marked downregulation of interleukin (IL)-6 protein and Il6 mRNA levels. This apocarotenoid exhibited more potent inhibitory effects than its parent carotenoids, capsanthin and capsorubin. Furthermore, apo-12'-capsorubinal, but not its parent carotenoids, promoted the nuclear accumulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and upregulated the expression of Nrf2-target genes, such as heme oxygenase 1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO-1), in a dose-dependent manner. Furthermore, a comparison using apo-12'-zeaxanthinal and 7,8-dihydro-8-oxo-apo-12'-zeaxanthinal revealed that the α, ß-unsaturated carbonyl group on the polyene linear chain mediated the enhanced nuclear Nrf2 translocation, HO-1 expression, and inhibition of IL-6 production. In contrast, apo-12'-mytiloxanthinal, which harbored a hydroxyl group at C-8 of apo-12'-capsorubinal, did not exhibit any of these activities. These results indicated that the ß carbon of the α, ß-unsaturated carbonyl group in the linear part of the polyene chain is crucial to the Nrf2-activating and anti-inflammatory effects of apo-12'-capsorubinal. This study will advance our knowledge of the physiological significance of xanthophyll-derived apocarotenoids and their potential use as nutraceuticals and pharmaceuticals.

Characterization of carotenoids extracted from Haloferax larsenii NCIM 5678 isolated from Pachpadra salt lake, Rajasthan.

Carotenoids are a diverse group of pigments known for their broad range of biological functions and applications. This study delves into multifaceted potential of carotenoids extracted from Haloferax larsenii NCIM 5678 previously isolated from Pachpadra Salt Lake in Rajasthan, India. H. larsenii NCIM 5678 was able to grow up to OD600 1.77 ± 0.03 with carotenoid concentration, 3.3 ± 0.03 µg/ml. The spectrophotometric analysis of carotenoid extract indicated the presence of three-fingered peak (460, 490 and 520 nm) which is a characteristic feature of bacterioruberin and its derivatives. The bacterioruberin was purified using silica gel column chromatography and thin layer chromatography. The carotenoid extract showed 12.3 ± 0.09 mm zone of growth inhibition with a minimum inhibitory concentration 546 ng/ml against indicator strain, H. larsenii HA4. The percentage antioxidant activity of carotenoid was found to be 84% which was higher as compared to commercially available ascorbic acid (56.74%). Thus, carotenoid extract from H. larsenii NCIM 5678 possesses unique attributes with compelling evidence of antimicrobial and antioxidant potential for the development of novel pharmaceuticals and nutraceuticals.

Enhancing the purification of crocin-I from saffron through the combination of multicolumn countercurrent chromatography and green solvents.

Crocin-I, a valuable natural compound found in saffron (Crocus sativus L.), is the most abundant among the various crocin structures. Developing a cost-effective and scalable purification process to produce high-purity crocin-I is of great interest for future investigations into its biological properties and its potential applications in the treatment of neurological disorders. However purifying crocin-I through single-column preparative chromatography (batch) poses a yield-purity trade-off due to structural similarities among crocins, meaning that the choice of the collection window sacrifices either yield in benefit of higher purity or vice versa. This study demonstrates how the continuous countercurrent operating mode resolves this dilemma. Herein, a twin-column MCSGP (multicolumn countercurrent solvent gradient purification) process was employed to purify crocin-I. This study involved an environmentally friendly ethanolic extraction of saffron stigma, followed by an investigation into the stability of the crocin-I within the feed under varying storage conditions to ensure a stable feed composition during the purification. Then, the batch purification process was initially designed, optimized, and subsequently followed by the scale-up to the MCSGP process. To ensure a fair comparison, both processes were evaluated under similar conditions (e.g., similar total column volume). The results showed that, at a purity grade of 99.7%, the MCSGP technique demonstrated significant results, namely + 334% increase in recovery + 307% increase in productivity, and - 92% reduction in solvent consumption. To make the purification process even greener, the only organic solvent employed was ethanol, without the addition of any additive. In conclusion, this study presents the MCSGP as a reliable, simple, and economical technique for purifying crocin-I from saffron extract, demonstrating for the first time that it can be effectively applied as a powerful approach for process intensification in the purification of natural products from complex matrices.

Ultrafast spectroscopy of the hydrophilic carotenoid crocin at various pH.

This study delves into the pH-dependent effects on the excited-state behavior of crocin, a hydrophilic carotenoid with diverse functions in biological systems. Steady-state spectroscopy demonstrates notable changes in absorption and fluorescence spectra, characterized by a pH-dependent blue shift and altered resolution of vibrational bands. Transient absorption spectra further elucidate these effects, highlighting a significant blue shift in the S1-Sn peak with increasing pH. Detailed kinetic analysis shows the pH-dependent dynamics of crocin's excited states. At pH 11, a shortening of effective conjugation is observed, resulting in a prolonged S1/ICT lifetime. Conversely, at pH 9, our data suggest a more complex scenario, suggesting the presence of two distinct crocin species with different relaxation patterns. This implies structural alterations within the crocin molecule, potentially linked to the deprotonation of hydroxyl groups in crocin and/or saponification at high pH.

Efficient delivery of carotenoids to adipocytes with albumin.

Carotenoids are very effectively delivered by albumin to adipocytes. The uptake of carotenoids to the cells occurs in the form of self-aggregates that localize in the vicinity of the adipocyte membrane, as shown by high spatial resolution Raman spectroscopy. The binding of carotenoids to albumin and the mechanism of their transport were elucidated with the help of chiroptical spectroscopies, in tandem with molecular docking and molecular dynamics simulations. In particular, apart from the recognized high affinity pocket of albumin that binds a carotenoid monomer in domain I, we have identified a hydrophobic periphery area in domain IIIB that loosely bounds the self-aggregated carotenoid in aqueous media and enables its easy detachment in hydrophobic environments. This explains the effectiveness of albumins as nanocarriers of carotenoids to adipocytes in vitro.

Predicting Solvatochromism of Chromophores in Proteins through QM/MM and Machine Learning.

Solvatochromism occurs in both homogeneous solvents and more complex biological environments, such as proteins. While in both cases the solvatochromic effects report on the surroundings of the chromophore, their interpretation in proteins becomes more complicated not only because of structural effects induced by the protein pocket but also because the protein environment is highly anisotropic. This is particularly evident for highly conjugated and flexible molecules such as carotenoids, whose excitation energy is strongly dependent on both the geometry and the electrostatics of the environment. Here, we introduce a machine learning (ML) strategy trained on quantum mechanics/molecular mechanics calculations of geometrical and electrochromic contributions to carotenoids' excitation energies. We employ this strategy to compare solvatochromism in protein and solvent environments. Despite the important specifities of the protein, ML models trained on solvents can faithfully predict excitation energies in the protein environment, demonstrating the robustness of the chosen descriptors.

Unveiling the potential of Pseudococcomyxa simplex: a stepwise extraction for cosmetic applications.

Microalgae are gaining attention as they are considered green fabrics able to synthesize many bioactive metabolites, with unique biological activities. However, their use at an industrial scale is still a challenge because of the high costs related to upstream and downstream processes. Here, a biorefinery approach was proposed, starting from the biomass of the green microalga Pseudococcomyxa simplex for the extraction of two classes of molecules with a potential use in the cosmetic industry. Carotenoids were extracted first by an ultrasound-assisted extraction, and then, from the residual biomass, lipids were obtained by a conventional extraction. The chemical characterization of the ethanol extract indicated lutein, a biosynthetic derivative of α-carotene, as the most abundant carotenoid. The extract was found to be fully biocompatible on a cell-based model, active as antioxidant and with an in vitro anti-aging property. In particular, the lutein-enriched fraction was able to activate Nrf2 pathway, which plays a key role also in aging process. Finally, lipids were isolated from the residual biomass and the isolated fatty acids fraction was composed by palmitic and stearic acids. These molecules, fully biocompatible, can find application as emulsifiers and softener agents in cosmetic formulations. Thus, an untapped microalgal species can represent a sustainable source for cosmeceutical formulations. KEY POINTS: • Pseudococcomyxa simplex has been explored in a cascade approach. • Lutein is the main extracted carotenoid and has antioxidant and anti-aging activity. • Fatty acids are mainly composed of palmitic and stearic acids.

Aster la vista: Unraveling the biochemical basis of carotenoid homeostasis in the human retina.

Carotenoids play pivotal roles in vision as light filters and precursor of chromophore. Many vertebrates also display the colorful pigments as ornaments in bare skin parts and feathers. Proteins involved in the transport and metabolism of these lipids have been identified including class B scavenger receptors and carotenoid cleavage dioxygenases. Recent research implicates members of the Aster protein family, also known as GRAM domain-containing (GRAMD), in carotenoid metabolism. These multi-domain proteins facilitate the intracellular movement of carotenoids from their site of cellular uptake by scavenger receptors to the site of their metabolic processing by carotenoid cleavage dioxygenases. We provide a model how the coordinated interplay of these proteins and their differential expression establishes carotenoid distribution patterns and function in tissues, with particular emphasis on the human retina.

Content of Primary and Secondary Carotenoids in the Cells of Cryotolerant Microalgae Chloromonas reticulata.

Snow (cryotolerant) algae often form red (pink) spots in mountain ecosystems on snowfields around the world, but little is known about their physiology and chemical composition. Content and composition of pigments in the cells of the cryotolerant green microalgae Chloromonas reticulata have been studied. Analysis of carotenoids content in the green (vegetative) cells grown under laboratory conditions and in the red resting cells collected from the snow surface in the Subpolar Urals was carried out. Carotenoids such as neoxanthin, violaxanthin, anteraxanthin, zeaxanthin, lutein, and ß-carotene were detected. Among the carotenoids, the ketocarotenoid astaxanthin with high biological activity was also found. It was established that cultivation of the algae at low positive temperature (6°C) and moderate illumination (250 µmol quanta/(m2⋅s) contributed to accumulation of all identified carotenoids, including extraplastidic astaxanthin. In addition to the pigments, fatty acids accumulated in the algae cells. The data obtained allow us to consider the studied microalgae as a potentially promising species for production of carotenoids.

Biotechnological potential of red yeast isolated from birch forests in Poland.

OBJECTIVES: This study aimed to isolate red yeast from sap, bark and slime exudates collected from Polish birch forests and then assessment of their biotechnological potential. RESULTS: 24 strains of red yeast were isolated from the bark, sap and spring slime fluxes of birch (Betula pendula). Strains belonging to Rhodotorula mucilaginosa (6), Rhodosporidiobolus colostri (4), Cystrofilobasidium capitaum (3), Phaffia rhodozyma (3) and Cystobasidium psychroaquaticum (3) were dominant. The highest efficiency of carotenoid biosynthesis (5.04 mg L-1) was obtained by R. mucilaginosa CMIFS 004, while lipids were most efficiently produced by two strains of P. rhodozyma (5.40 and 5.33 g L-1). The highest amount of exopolysaccharides (3.75 g L-1) was produced by the R. glutinis CMIFS 103. Eleven strains showed lipolytic activity, nine amylolytic activity, and only two proteolytic activity. The presence of biosurfactants was not found. The growth of most species of pathogenic moulds was best inhibited by Rhodotorula yeasts. CONCLUSION: Silver birch is a good natural source for the isolation of new strains of red yeast with wide biotechnological potential.

Microbial bacterioruberin: The new C50 carotenoid player in food industries.

The demand for natural products has significantly increased, driving interest in carotenoids as bioactive compounds for both human and animal consumption. Carotenoids, natural pigments with several biological properties, like antioxidant and antimicrobial, are increasingly preferred over synthetic colorants by the consumers (chemophobia). The global carotenoid market is projected to reach US$ 2.45 billion by 2034, driven by consumer preferences for natural ingredients and regulatory restrictions on synthetic products. Among carotenoids, bacterioruberin (BR), a C50 carotenoid naturally found in microbial hyperhalophilic archaea and in moderate halophilic archaea, stands out for its exceptional antioxidant capabilities, surpassing even well-known carotenoids like astaxanthin. BR's and its derivatives unique structure, with 13 conjugated double bonds and four -OH groups, contributes to its potent antioxidant activity and potential applications in food, feed, supplements, pharmaceuticals, and cosmeceuticals. This review explores BR's chemical and biological properties, upstream and downstream technologies, analytical techniques, market applications, and prospects in the colorants industry. While BR is not intended to replace existing carotenoids, its inclusion enriches the range of natural products available to meet the rising demand for natural alternatives. Furthermore, BR's promising antioxidant capacity positions it as a key player in the future carotenoid market, offering diverse industries a natural and potent alternative for several applications.

Dehydration, Rehydration and Thermal Treatment: Effect on Bioactive Compounds of Red Seaweeds Porphyra umbilicalis and Porphyra linearis.

The nutritional and bioactive value of seaweeds is widely recognized, making them a valuable food source. To use seaweeds as food, drying and thermal treatments are required, but these treatments may have a negative impact on valuable bioactive compounds. In this study, the effects of dehydration, rehydration, and thermal treatment on the bioactive compounds (carotenoids, phycobiliproteins, total phenolic content (TPC), total flavonoids content (TFC)), antioxidant (ABTS and DPPH radical scavenging activities) and anti-Alzheimer's (Acetylcholinesterase (AchE) inhibitory activities, and color properties of Porphyra umbilicalis and Porphyra linearis seaweeds were evaluated. The results revealed significant reductions in carotenoids, TPC, TFC, and antioxidant activities after the seaweeds' processing, with differences observed between species. Thermal treatment led to the most pronounced reductions in bioactive compound contents and antioxidant activity. AchE inhibitory activity remained relatively high in all samples, with P. umbilicalis showing higher activity than P. linearis. Changes in color (ΔE) were significant after seaweeds' dehydration, rehydration and thermal treatment, especially in P. umbilicalis. Overall, optimizing processing methods is crucial for preserving the bioactive compounds and biological activities of seaweeds, thus maximizing their potential as sustainable and nutritious food sources or as nutraceutical ingredients.

Bacterioruberin: Biosynthesis, Antioxidant Activity, and Therapeutic Applications in Cancer and Immune Pathologies.

Halophilic archaea, also termed haloarchaea, are a group of moderate and extreme halophilic microorganisms that constitute the major microbial populations in hypersaline environments. In these ecosystems, mainly aquatic, haloarchaea are constantly exposed to ionic and oxidative stress due to saturated salt concentrations and high incidences of UV radiation (mainly in summer). To survive under these harsh conditions, haloarchaea have developed molecular adaptations including hyperpigmentation. Regarding pigmentation, haloarchaeal species mainly synthesise the rare C50 carotenoid called bacterioruberin (BR) and its derivatives, monoanhydrobacterioruberin and bisanhydrobacterioruberin. Due to their colours and extraordinary antioxidant properties, BR and its derivatives have been the aim of research in several research groups all over the world during the last decade. This review aims to summarise the most relevant characteristics of BR and its derivatives as well as describe their reported antitumoral, immunomodulatory, and antioxidant biological activities. Based on their biological activities, these carotenoids can be considered promising natural biomolecules that could be used as tools to design new strategies and/or pharmaceutical formulas to fight against cancer, promote immunomodulation, or preserve skin health, among other potential uses.