Fluorescence capturing behaviour of cyanobacterial resilience: Insights into UV-exposed ecosystems and its environmental applications.

Cyanobacteria are resilient microorganisms and thrive in environments exposed to UV radiation, ranging from ocean surfaces to scorching hot springs and dry expanses. 'Cyanobacterial Resilience' refers to their ability to withstand UV radiation, revealing intricate genomic secrets and adaptive mechanisms ensuring survival. These mechanisms include metabolic adaptations, robust DNA repair systems and UV-protective compounds such as Scytonemin and Mycosporine, vital for shielding against UV radiation survival. Cyanobacteria are crucial pioneers in UV-exposed ecosystems, highlighting their resilience and adaptability. Some cyanobacteria exhibit luminescence, emitting blue-green light due to phycobiliproteins, while bioluminescence in cyanobacteria, if it occurs, involves different compounds rather than luciferins and luciferase enzymes. This luminescence holds promise for various biotechnological applications, such as biosensors, imaging probes and carbon sequestration, for participating in photocatalytic processes for water purification and CO2 conversion, and contributes to solar simulation studies to advance photosynthesis and renewable energy technologies. The versatile applications of these materials highlight their ecological importance and potential in addressing global challenges. In conclusion, 'Cyanobacterial Resilience' highlights the remarkable adaptation strategies of cyanobacteria in UV-exposed environments. It emphasises their role as pioneers and innovators in biological and technological domains, providing insights into their enduring impact on ecosystems and scientific advancement.

Resilience and Mitigation Strategies of Cyanobacteria under Ultraviolet Radiation Stress.

Ultraviolet radiation (UVR) tends to damage key cellular machinery. Cells may adapt by developing several defence mechanisms as a response to such damage; otherwise, their destiny is cell death. Since cyanobacteria are primary biotic components and also important biomass producers, any drastic effects caused by UVR may imbalance the entire ecosystem. Cyanobacteria are exposed to UVR in their natural habitats. This exposure can cause oxidative stress which affects cellular morphology and vital processes such as cell growth and differentiation, pigmentation, photosynthesis, nitrogen metabolism, and enzyme activity, as well as alterations in the native structure of biomolecules such as proteins and DNA. The high resilience and several mitigation strategies adopted by a cyanobacterial community in the face of UV stress are attributed to the activation of several photo/dark repair mechanisms, avoidance, scavenging, screening, antioxidant systems, and the biosynthesis of UV photoprotectants, such as mycosporine-like amino acids (MAAs), scytonemin (Scy), carotenoids, and polyamines. This knowledge can be used to develop new strategies for protecting other organisms from the harmful effects of UVR. The review critically reports the latest updates on various resilience and defence mechanisms employed by cyanobacteria to withstand UV-stressed environments. In addition, recent developments in the field of the molecular biology of UV-absorbing compounds such as mycosporine-like amino acids and scytonemin and the possible role of programmed cell death, signal perception, and transduction under UVR stress are discussed.

Identification of Cyanobacteria-Based Natural Inhibitors Against SARS-CoV-2 Druggable Target ACE2 Using Molecular Docking Study, ADME and Toxicity Analysis.

In 2019-2020, the novel "severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)" had emerged as the biggest challenge for humanity, causing "coronavirus disease 19 (COVID-19)". Scientists around the world have been putting continuous efforts to unfold potential inhibitors of SARS-CoV-2. We have performed computational studies that help us to identify cyanobacterial photoprotective compounds as potential inhibitors against SARS-CoV-2 druggable target human angiotensin-converting enzyme (ACE2), which plays a vital role in the attachment and entry of the virus into the cell. Blocking the receptor-binding domain of ACE2 can prevent the access of the virus into the compartment. A molecular docking study was performed between photoprotective compounds mycosporine-like amino acids, scytonemins and ACE2 protein using AutoDock tools. Among sixteen molecularly docked metabolites, seven compounds were selected with binding energy < 6.8 kcal/mol. Afterwards, drug-likeness and toxicity of the top candidate were predicted using Swiss ADME and Pro Tox-II online servers. All top hits show desirable drug-likeness properties, but toxicity pattern analysis discloses the toxic effect of scytonemin and its derivatives, resulting in the elimination from the screening pipeline. Further molecular interaction study of the rest two ligands, mycosporine-glycine-valine and shinorine with ACE2 was performed using PyMol, Biovia Discovery studio and LigPlot+. Lastly biological activity of both the ligands was predicted by using the PASS online server. Combining the docking score and other studied properties, we believe that mycosporine-glycine-valine and shinorine have potential to be potent inhibitors of ACE2 and can be explored further to use against COVID-19.

Microalgae Photo-Protectants and Related Bio-Carriers Loaded with Bioactive Entities for Skin Applications-An Insight of Microalgae Biotechnology.

Microalgae are photosynthetic organisms known for producing valuable metabolites under different conditions such as extreme temperatures, high salinity, osmotic pressure, and ultraviolet radiation. In recent years, these metabolites have become a trend due to their versatility in applications such as pharmaceuticals, cosmetics, and others. They have even been proposed as an alternative source of bioactive metabolites to avoid the harmful effects on the environment produced by active compounds such as oxybenzone in commercials sunscreens. One of the most studied applications is the use of microalgae for skin care and topical use as cosmeceuticals. With the increasing demand for more environmentally friendly products in cosmetics, microalgae have been further explored in relation to this application. It has been shown that some microalgae are resistant to UV rays due to certain compounds such as mycosporine-like amino acids, sporopollenin, scytonemin, and others. These compounds have different mechanisms of action to mitigate UV damage induced. Still, they all have been proven to confer UV tolerance to microalgae with an absorbance spectrum like the one in conventional sunscreens. This review focuses on the use of these microalgae compounds obtained by UV stimulation and takes advantage of their natural UV-resistant characteristics to potentially apply them as an alternative for UV protection products.

Biotechnological Production of the Sunscreen Pigment Scytonemin in Cyanobacteria: Progress and Strategy.

Scytonemin is a promising UV-screen and antioxidant small molecule with commercial value in cosmetics and medicine. It is solely biosynthesized in some cyanobacteria. Recently, its biosynthesis mechanism has been elucidated in the model cyanobacterium Nostoc punctiforme PCC 73102. The direct precursors for scytonemin biosynthesis are tryptophan and p-hydroxyphenylpyruvate, which are generated through the shikimate and aromatic amino acid biosynthesis pathway. More upstream substrates are the central carbon metabolism intermediates phosphoenolpyruvate and erythrose-4-phosphate. Thus, it is a long route to synthesize scytonemin from the fixed atmospheric CO2 in cyanobacteria. Metabolic engineering has risen as an important biotechnological means for achieving sustainable high-efficiency and high-yield target metabolites. In this review, we summarized the biochemical properties of this molecule, its biosynthetic gene clusters and transcriptional regulations, the associated carbon flux-driving progresses, and the host selection and biosynthetic strategies, with the aim to expand our understanding on engineering suitable cyanobacteria for cost-effective production of scytonemin in future practices.

Raman imaging of microbial colonization in rock-some analytical aspects.

Raman imaging allows one to obtain spatially resolved chemical information in a nondestructive manner. Herein, we present analytical aspects of effective in situ and in vivo Raman imaging of algae and cyanobacteria from within their native rock habitats. Specifically, gypsum and halite inhabited by endolithic communities from the hyperarid Atacama Desert were analyzed. Raman imaging of these phototrophic colonization reveals a pigment composition within the aggregates that helps in understanding some of their adaptation strategies to survive in this harsh polyextreme environment. The study is focused on methodical aspects of Raman imaging acquisition and subsequent data processing. Point imaging is compared with line imaging in terms of their image quality, spatial resolution, spectral signal-to-noise ratio, time requirements, and risk of laser-induced sample alteration. The roles of excitation wavelength, exposure time, and step size of the imaging grid on successful Raman imaging results are also discussed. Graphical abstract.

Inhibition of Skin Inflammation by Scytonemin, an Ultraviolet Sunscreen Pigment.

Scytonemin is a yellow-green ultraviolet sunscreen pigment present in different genera of aquatic and terrestrial blue-green algae, including marine cyanobacteria. In the present study, the anti-inflammatory activities of scytonemin were evaluated in vitro and in vivo. Topical application of scytonemin inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ear swelling in BALB/c mice. The expression of tumor necrosis factor-a (TNF-a) and inducible nitric oxide synthase (iNOS) was also suppressed by scytonemin treatment in the TPA-treated ear of BALB/c mice. In addition, scytonemin inhibited lipopolysaccharide (LPS)-induced production of TNF-a and nitric oxide (NO) in RAW 264.7 cells, a murine macrophage-like cell line, and the mRNA expressions of TNF-a and iNOS were also suppressed by scytonemin in LPS-stimulated RAW 264.7 cells. Further study demonstrated that LPS-induced NF-kB activity was significantly suppressed by scytonemin treatment in RAW 264.7 cells. Our results also showed that the degradation of IkBa and nuclear translocation of the p65 subunit were blocked by scytonemin in LPS-stimulated RAW 264.7 cells. Collectively, these results suggest that scytonemin inhibits skin inflammation by blocking the expression of inflammatory mediators, and the anti-inflammatory effect of scytonemin is mediated, at least in part, by down-regulation of NF-kB activity. Our results also suggest that scytonemin might be used as a multi-function skin care ingredient for UV protection and anti-inflammation.

Cyanobacteria and Red Macroalgae as Potential Sources of Antioxidants and UV Radiation-Absorbing Compounds for Cosmeceutical Applications.

In recent years, research on natural products has gained considerable attention, particularly in the cosmetic industry, which is looking for new bio-active and biodegradable molecules. In this study, cosmetic properties of cyanobacteria and red macroalgae were analyzed. The extractions were conducted in different solvents (water, ethanol and two combinations of water:ethanol). The main molecules with antioxidant and photoprotective capacity were mycosporine-like amino acids (MAAs), scytonemin and phenolic compounds. The highest contents of scytonemin (only present in cyanobacteria) were observed in Scytonema sp. (BEA 1603B) and Lyngbya sp. (BEA 1328B). The highest concentrations of MAAs were found in the red macroalgae Porphyra umbilicalis, Gelidium corneum and Osmundea pinnatifida and in the cyanobacterium Lyngbya sp. Scytonema sp. was the unique species that presented an MAA with maximum absorption in the UV-B band, being identified as mycosporine-glutaminol for the first time in this species. The highest content of polyphenols was observed in Scytonema sp. and P. umbilicalis. Water was the best extraction solvent for MAAs and phenols, whereas scytonemin was better extracted in a less polar solvent such as ethanol:dH2O (4:1). Cyanobacterium extracts presented higher antioxidant activity than those of red macroalgae. Positive correlations of antioxidant activity with different molecules, especially polyphenols, biliproteins and MAAs, were observed. Hydroethanolic extracts of some species incorporated in creams showed an increase in the photoprotection capacity in comparison with the base cream. Extracts of these organisms could be used as natural photoprotectors improving the diversity of sunscreens. The combination of different extracts enriched in scytonemin and MAAs could be useful to design broad-band natural UV-screen cosmeceutical products.

Scytonemin Plays a Potential Role in Stabilizing the Exopolysaccharidic Matrix in Terrestrial Cyanobacteria.

Cyanobacteria are photosynthetic oxygen-evolving prokaryotes that are distributed in diverse habitats. They synthesize the ultraviolet (UV)-screening pigments, scytonemin (SCY) and mycosporine-like amino acids (MAAs), located in the exopolysaccharide (EPS) matrix. Multiple roles for both pigments have gradually been recognized, such as sunscreen ability, antioxidant activity, and heat dissipation from absorbed UV radiation. In this study, a filamentous terrestrial cyanobacterium Nostoc flagelliforme was used to evaluate the potential stabilizing role of SCY on the EPS matrix. SCY (∼3.7 %) was partially removed from N. flagelliforme filaments by rinsing with 100 % acetone for 5 s. The physiological damage to cells resulting from this treatment, in terms of photosystem II activity parameter Fv/Fm, was repaired after culturing the sample for 40 h. The physiologically recovered sample was further desiccated by natural or rapid drying and then allowed to recovery for 24 h. Compared with the normal sample, a relatively slower Fv/Fm recovery was observed in the SCY-partially removed sample, suggesting that the decreased SCY concentration in the EPS matrix caused cells to suffer further damage upon desiccation. In addition, the SCY-partially removed sample could allow the release of MAAs (∼25 %) from the EPS matrix, while the normal sample did not. Therefore, damage caused by drying of the former resulted from at least the reduction of structural stability of the EPS matrix as well as the loss of partial antioxidant compounds. Considering that an approximately 4 % loss of SCY led to this significant effect, the structurally stabilizing potential of SCY on the EPS matrix is crucial for terrestrial cyanobacteria survival in complex environments.

Raman spectroscopic analysis of the effect of the lichenicolous fungus Xanthoriicola physciae on its lichen host.

Lichenicolous (lichen-dwelling) fungi have been extensively researched taxonomically over many years, and phylogenetically in recent years, but the biology of the relationship between the invading fungus and the lichen host has received limited attention, as has the effects on the chemistry of the host, being difficult to examine in situ. Raman spectroscopy is an established method for the characterization of chemicals in situ, and this technique is applied to a lichenicolous fungus here for the first time. Xanthoriicola physciae occurs in the apothecia of Xanthoria parietina, producing conidia at the hymenium surface. Raman spectroscopy of apothecial sections revealed that parietin and carotenoids were destroyed in infected apothecia. Those compounds protect healthy tissues of the lichen from extreme insolation and their removal may contribute to the deterioration of the apothecia. Scytonemin was also detected, but was most probably derived from associated cyanobacteria. This work shows that Raman spectroscopy has potential for investigating changes in the chemistry of a lichen by an invading lichenicolous fungus.

The response regulator Npun_F1278 is essential for scytonemin biosynthesis in the cyanobacterium Nostoc punctiforme ATCC 29133.

Following exposure to long-wavelength ultraviolet radiation (UVA), some cyanobacteria produce the indole-alkaloid sunscreen scytonemin. The genomic region associated with scytonemin biosynthesis in the cyanobacterium Nostoc punctiforme includes 18 cotranscribed genes. A two-component regulatory system (Npun_F1277/Npun_F1278) directly upstream from the biosynthetic genes was identified through comparative genomics and is likely involved in scytonemin regulation. In this study, the response regulator (RR), Npun_F1278, was evaluated for its ability to regulate scytonemin biosynthesis using a mutant strain of N. punctiforme deficient in this gene, hereafter strain Δ1278. Following UVA radiation, the typical stimulus to initiate scytonemin biosynthesis, Δ1278 was incapable of producing scytonemin. A phenotypic characterization of Δ1278 suggests that aside from the ability to produce scytonemin, the deletion of the Npun_F1278 gene does not affect the cellular morphology, cellular differentiation capability, or lipid-soluble pigment complement of Δ1278 compared to the wildtype. The mutant, however, had a slower specific growth rate under white light and produced ~2.5-fold more phycocyanin per cell under UVA than the wildtype. Since Δ1278 does not produce scytonemin, this study demonstrates that the RR gene, Npun_F1278, is essential for scytonemin biosynthesis in N. punctiforme. While most of the evaluated effects of this gene appear to be specific for scytonemin, this regulator may also influence the overall health of the cell and phycobiliprotein synthesis, directly or indirectly. This is the first study to identify a regulatory gene involved in the biosynthesis of the sunscreen scytonemin and posits a link between cell growth, pigment synthesis, and sunscreen production.

The role of the protective shield against UV-C radiation and its molecular interactions in Nostoc species (Cyanobacteria).

Cyanobacteria possess special defense mechanisms to protect themselves against ultraviolet (UV) radiation. This study combines experimental and computational methods to identify the role of protective strategies in Nostoc species against UV-C radiation. To achieve this goal, various species of the genus Nostoc from diverse natural habitats in Iran were exposed to artificial UV-C radiation. The results indicated that UV-C treatment significantly reduced the photosynthetic pigments while simultaneously increasing the activity of antioxidant enzymes. Notably, N. sphaericum ISB97 and Nostoc sp. ISB99, the brown Nostoc species isolated from habitats with high solar radiations, exhibited greater resistance compared to the green-colored species. Additionally, an increase in scytonemin content occurred with a high expression of key genes associated with its synthesis (scyF and scyD) during the later stages of UV-C exposure in these species. The molecular docking of scytonemin with lipopolysaccharides of the cyanobacteria that mainly cover the extracellular matrix revealed the top/side positioning of scytonemin on the glycans of these lipopolysaccharides to form a UV-protective shield. These findings pave the way for exploring the molecular effects of scytonemin in forming the UV protection shield in cyanobacteria, an aspect that has been ambiguous until now.

Evaluating Pigments as a Biosignature: Abiotic/Prebiotic Synthesis of Pigments and Pigment Mimics in Planetary Environments.

Pigments serve a multitude of functions in biology including light harvesting for photosynthesis, radiation protection, membrane support, and defense. The ubiquity of pigments-especially within extremophiles found in high-radiation, high-salinity, and dry environments-and their detectability via mission-ready techniques have elevated these molecules as promising targets in the search for evidence of life elsewhere. Moreover, the detection of pigments has been proposed as a "smoking gun" for extraterrestrial life as it has been suggested that these molecules cannot be generated abiotically. However, while pigments may hold promise as a biosignature, current understanding of their possible prebiotic origins remains understudied and uncertain. Better understanding of the abiotic synthesis of pigments is critical for evaluating the biogenicity of any pigment detected during missions, including by the Mars Perseverance rover or from returned samples. Compounding this uncertainty is the broad definition of pigment as it includes any compound capable of absorbing visible light and by itself does not specify a particular chemical motif. While not experimentally verified, there are promising prebiotic routes for generating pigments including hemes, chlorophylls, and carotenoids. Herein, we review the biochemistry of pigments, the inherent assumptions made when searching for these molecules in the field, their abiotic synthesis in industry and prebiotic reactions, prebiotically relevant molecules that can mimic their spectral signatures, and implications/recommendations for future work.

Scytonin in gypsum endolithic colonisation: First Raman spectroscopic detection of a new spectral biosignature for terrestrial astrobiological analogues and for exobiological mission database extension.

Microbial colonisations of gypsum from Eastern Poland (Badenian, Middle Miocene age) were investigated by Raman microspectrometry with a rarely used excitation 445 nm excitation. Zones of microbial colonisation in selenitic gypsum endolithic outcrops comprise algae and cyanobacteria, which commonly contain the photosynthetic and protective pigments carotenoids, scytonemin and gloeocapsin. Diagnostic bands differing from those of scytonemin have been identified in black colonies in gypsum outcrops at Chotel Czierwony (Poland). Raman spectral signatures of scytonin are reported here for the first time in two endolithic specimens identified by the band wavenumbers predicted from DFT calculations. The strong or medium strong intensity Raman bands observed at 1603, 1585, 1559, 1435, and 1424 cm-1. Other weaker bands were located at 1676 (sh), 1660 (sh), 1649, 1399, 1362, 1342, 1320, 1294, 1272, 1259, and 1052 cm-1. The first observation of the Raman spectrum of scytonin in the cyanobacterial colonisation of gypsum facilitates the inclusion of this new biomolecular signature in the library of unique Raman spectra of biological pigments invaluable for detection of traces of life in frame of the planetary missions.

In silico exploration and in vitro validation of the filarial thioredoxin reductase inhibitory activity of Scytonemin and its derivatives.

Lymphatic filariasis (LF) caused by the vector borne parasitic nematode Wuchereria bancrofti is of major concern of the World Health Organization (WHO). Lack of potential drug candidates worsens the situation. Presently available drugs are promising in killing the microfilaria (mf) but are not effective as adulticidal therapeutics. Previous studies have revealed that routine administration of the available drugs (albendazole, ivermectin and albendazole) sometime is associated with severe adverse effects (SAEs) in co-infection state. Therefore, potential and safe therapeutics are still required. Earlier studies on filarial thioredoxin reductase (TrxR) have shown that successful inhibition of it can lead to apoptotic death of the parasites. TrxR in filarial parasites plays a significant role in disease progression and pathogenesis, hence efficient non-reversible inhibition of TrxR can be a good strategy to treat LF. In this research, inhibitory potential of Scytonemin, a cyanobacterial metabolite on filarial TrxR was evaluated via different in silico methods and validated through in vitro experiments. Parasite death upon exposure to Scytonemin can be correlated with the TrxR inhibiting capacity of the compound. Therefore, this cyanobacterial-derived compound may possibly be used further as novel and safe therapeutic candidate against filarial infection.Communicated by Ramaswamy H. Sarma.

Scytonemin redox status in a filamentous cyanobacterium visualized by an excitation-laser-line-scanning spontaneous Raman scattering spectral microscope.

Some cyanobacteria produce a UVA-absorbing pigment, scytonemin, at extracellular sheaths. Although scytonemin-containing dark sheaths are recognizable through optical microscopes and its redox changes have been known for decades, there has been no report to obtain images of both oxidized and reduced scytonemins at subcellular resolution. Here, we show that a spontaneous Raman scattering spectral microscopy based on an excitation-laser-line-scanning method unveil 3D subcellular distributions of both the oxidized and reduced scytonemins in a filamentous cyanobacterium. The redox changes of scytonemin were supported by comparison in the Raman spectra between the cyanobacterial cells, solid-state scytonemin and quantum chemical normal mode analysis. Distributions of carotenoids, phycobilins, and the two redox forms of scytonemin were simultaneously visualized with an excitation wavelength at 1064 nm that is virtually free from the optical screening by the dark sheaths. The redox differentiation of scytonemin will advance our understanding of the redox homeostasis and secretion mechanisms of individual cyanobacteria as well as microscopic chemical environments in various microbial communities. The line-scanning Raman microscopy based on the 1064 nm excitation is thus a promising tool for exploring hitherto unreported Raman spectral features and distribution of nonfluorescent molecules embedded below nontransparent layers for visible light, while avoiding interference by autofluorescence.

Expression of Scytonemin Biosynthesis Genes under Alternative Stress Conditions in the Cyanobacterium Nostoc punctiforme.

The indole-alkaloid scytonemin is a sunscreen pigment that is widely produced among cyanobacteria as an ultraviolet radiation (UVR) survival strategy. Scytonemin biosynthesis is encoded by two gene clusters that are known to be induced by long-wavelength radiation (UVA). Previous studies have characterized the transcriptome of cyanobacteria in response to a wide range of conditions, but the effect on the expression of scytonemin biosynthesis genes has not been specifically targeted. Therefore, the aim of this study is to determine the variable response of scytonemin biosynthesis genes to a variety of environmental conditions. Cells were acclimated to white light before supplementation with UVA, UVB, high light, or osmotic stress for 48 h. The presence of scytonemin was determined by absorbance spectroscopy and gene expression of representative scytonemin biosynthesis genes was measured using quantitative PCR. Scytonemin genes were up-regulated in UVA, UVB, and high light, although the scytonemin pigment was not detected under high light. There was no scytonemin or upregulation of these genes under osmotic stress. The lack of pigment production under high light, despite increased gene expression, suggests a time-dependent delay for pigment production or additional mechanisms or genes that may be involved in scytonemin production beyond those currently known.

Inferred ancestry of scytonemin biosynthesis proteins in cyanobacteria indicates a response to Paleoproterozoic oxygenation.

Protection from radiation damage is an important adaptation for phototrophic microbes. Living in surface, shallow water, and peritidal environments, cyanobacteria are especially exposed to long-wavelength ultraviolet (UVA) radiation. Several groups of cyanobacteria within these environments are protected from UVA damage by the production of the pigment scytonemin. Paleontological evidence of cyanobacteria in UVA-exposed environments from the Proterozoic, and possibly as early as the Archaean, suggests a long evolutionary history of radiation protection within this group. We show that phylogenetic analyses of enzymes in the scytonemin biosynthesis pathway support this hypothesis and reveal a deep history of vertical inheritance of this pathway within extant cyanobacterial diversity. Referencing this phylogeny to cyanobacterial molecular clocks suggests that scytonemin production likely appeared during the early Proterozoic, soon after the Great Oxygenation Event. This timing is consistent with an adaptive scenario for the evolution of scytonemin production, wherein the threat of UVA-generated reactive oxygen species becomes significantly greater once molecular oxygen is more pervasive across photosynthetic environments.

Discovery of Novel Tyrosinase Inhibitors From Marine Cyanobacteria.

Tyrosinase, an important oxidase involved in the primary immune response in humans, can sometimes become problematic as it can catalyze undesirable oxidation reactions. Therefore, for decades there has been a strong pharmaceutical interest in the discovery of novel inhibitors of this enzyme. Recent studies have also indicated that tyrosinase inhibitors can potentially be used in the treatment of melanoma cancer. Over the years, many new tyrosinase inhibitors have been discovered from various natural sources; however, marine natural products (MNPs) have contributed only a small number of promising candidates. Therefore, in this study we focused on the discovery of new MNP tyrosinase inhibitors of marine cyanobacterial and algal origins. A colorimetric tyrosinase inhibitory assay was used to screen over 4,500 marine extracts against mushroom tyrosinase (A. bisporus). Our results revealed that scytonemin monomer (ScyM), a pure compound from our compound library and also the monomeric last-step precursor in the biosynthesis of the well-known cyanobacterial sunscreen pigment "scytonemin," consistently showed the highest tyrosinase inhibitory score. Determination of the half maximal inhibitory concentration (IC50) further indicated that ScyM is more potent than the commonly used commercial inhibitor standard "kojic acid" (KA; IC50 of ScyM: 4.90 µM vs. IC50 of KA: 11.31 µM). After a scaled-up chemical synthesis of ScyM as well as its O-methyl analog (ScyM-OMe), we conducted a series of follow-up studies on their structures, inhibitory properties, and mode of inhibition. Our results supported ScyM as the second case ever of a novel tyrosinase inhibitory compound based on a marine cyanobacterial natural product. The excellent in vitro performance of ScyM makes it a promising candidate for applications such as a skin-whitening agent or an adjuvant therapy for melanoma cancer treatment.

Characterization of mycosporine-like amino acids in the edible cyanobacterium Nostoc commune (Di Pi Cai) from China.

The terrestrial cyanobacterium Nostoc commune has a cosmopolitan distribution. It is edible, and dry thalli are sold as a food in China under the name of Di Pi Cai. The pigment composition and the genotypes were characterized to identify the cyanobacterium Di Pi Cai from China as N. commune. Myxol glycosides and ketocarotenoids were detected, as expected in Nostoc sp., but ß-carotene and hydroxylated carotenoids were not detected. Nostoc-756, mycosporine-2-(4-deoxygadusoyl-ornitine), was found to be a main mycosporine-like amino acid, which indicates that Di Pi Cai belongs to the N. commune chemotype C. However, the 16S rRNA gene and the petH gene encoding ferredoxin-NADP+ oxidoreductase of Di Pi Cai did not exactly match those of genotype C found in Japan. These results suggest the unique molecular genetic features of Di Pi Cai and the global diversity of N. commune.