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Bioactive compounds produced by cyanobacteria
Abstract
Cyanobacteria produce a large number of compounds with varying bioactivities. Prominent among these are toxins: hepatotoxins such as microcystins and nodularins and neurotoxins such as anatoxins and saxitoxins. Cytotoxicity to tumor cells has been demonstrated for other cyanobacterial products, including 9-deazaadenosine, dolastatin 13 and analogs. A number of compounds in cyanobacteria are inhibitors of proteases — micropeptins, cyanopeptolins, oscillapeptin, microviridin, aeruginosins- and other enzymes, while still other compounds have no recognized biological activities. In general cyclic peptides and depsipeptides are the most common structural types, but a wide variety of other types are also found: linear peptides, guanidines, phosphonates, purines and macrolides. The close similarity or identity in structures between cyanobacterial products and compounds isolated from sponges, tunicates and other marine invertebrates suggests the latter compounds may be derived from dietary or symbiotic blue-green algae.
... Besides the toxins a lot of active substances with antibacterial, antiviral, fungicide, enzyme inhibiting, immunosuppressive, cytotoxic and algicide activity has been isolated from cyanobacterial biomass or in some cases from the medium of laboratory cultures (Falch, 1996;Namikoshi and Rinehart, 1996;Banker and Carmeli, 1998;Harrigan et al., 1998 andJaki et al., 1998 and. Producing active biocide components could be an important selective advantage. ...
... In the last decades screening programs have revealed that cyanobacteria are a potential source of new active substances for medicine and pharmacy and numerous active compounds have been isolated (Moore et al., 1989;Patterson et al., 1994;Falch, 1996Namikoshi and Rinehart, 1996;Papendorf et al., 1998;Kajiyama et al., 1998;Jaki et al., 1999;Singh et al., 1999;Luesch et al., 2000;Horgen et al., 2000). These active compounds could influence the aquatic environment of cyanobacteria by reducing the number of viruses, bacteria and other micoorganisms. ...
... This protease inhibition could be the reason for the inhibition of influenzavirus replication because the processing of virus proteins is an obligatory step in virus life cycle (Kido et al. 1992). In last years several protease inhibitors, cyclic and linear peptides, have been isolated from Microcystis aeruginosa strains (Namikoshi and Rinehart 1996), so that the antiviral effects may be caused by these peptides too. ...
... Besides the toxins a lot of active substances with antibacterial, antiviral, fungicide, enzyme inhibiting, immunosuppressive, cytotoxic and algicide activity has been isolated from cyanobacterial biomass or in some cases from the medium of laboratory cultures (Falch, 1996;Namikoshi and Rinehart, 1996;Banker and Carmeli, 1998;Harrigan et al., 1998 andJaki et al., 1998 and. Producing active biocide components could be an important selective advantage. ...
... In the last decades screening programs have revealed that cyanobacteria are a potential source of new active substances for medicine and pharmacy and numerous active compounds have been isolated (Moore et al., 1989;Patterson et al., 1994;Falch, 1996Namikoshi and Rinehart, 1996;Papendorf et al., 1998;Kajiyama et al., 1998;Jaki et al., 1999;Singh et al., 1999;Luesch et al., 2000;Horgen et al., 2000). These active compounds could influence the aquatic environment of cyanobacteria by reducing the number of viruses, bacteria and other micoorganisms. ...
... This protease inhibition could be the reason for the inhibition of influenzavirus replication because the processing of virus proteins is an obligatory step in virus life cycle (Kido et al. 1992). In last years several protease inhibitors, cyclic and linear peptides, have been isolated from Microcystis aeruginosa strains (Namikoshi and Rinehart 1996), so that the antiviral effects may be caused by these peptides too. ...
... Marine cyanobacteria have been attracting increasing attention for probe and drug discovery due to the high incidence of structurally novel bioactive secondary metabolites that complement those known from terrestrial sources [36][37][38]. These natural products are predominantly modified peptides and depsipeptides, polyketides, and peptide-polyketide hybrids, many of which are cyclic and oftentimes halogenated [39][40][41]. ...
... These natural products are predominantly modified peptides and depsipeptides, polyketides, and peptide-polyketide hybrids, many of which are cyclic and oftentimes halogenated [39][40][41]. Cyanobacteria produce many bioactive compounds of various chemical structures, with about 40% of them being lipopeptides [36][37][38][39][40][41][42][43][44][45]. ...
... It was shown that the natural product antillatoxin B (42) is 10 times less active than antillatoxin A (41), and synthetic stereoisomers (43 and 44) of the cyclic depsipeptide of antillatoxin A were 20-55 times less active than the natural isomer [125,126]. Both synthetic stereoisomers (43 and 44) contain different lipophilic fragments, (4S,5S,6E,8E)-5-hydroxy-4,6,10,10-tetramethyl-3-methyleneundeca-6,8-dienoic acid (38) and (4S,5S),(E)-5-hydroxy-4,6,10,10-tetramethyl-3-methyleneundec-6-enoic acid (39), respectively, although the cytotoxicity (44) for Neuro-2a cells was shown to be 10 times more effective than the cytotoxicity of the molecule (43) as shown by Okura and co-workers [127]. ...
The study of lipopeptides and their related compounds produced by various living organisms from bacteria to marine invertebrates is of fundamental interest for medicinal chemistry, pharmacology, and practical clinical medicine. Using the principles of retrosynthetic analysis of linear and cyclic peptides, the pharmacological activity of unique, unusual, and rare fatty acids (FA) that are part of natural lipopeptides was investigated. To search for new biologically active natural metabolites from natural sources, more than 350 FA incorporated into linear and cyclic peptides isolated from bacteria, cyanobacteria, microalgae, marine invertebrates, fungal endophytes, and microorganisms isolated from sediments are presented. Biological activities have been studied experimentally in various laboratories, as well as data obtained using QSAR (Quantitative Structure-Activity Relationships) algorithms. According to the data obtained, several FA were identified that demonstrated strong antibacterial, antimicrobial, antifungal, or antitumor activity. Along with this, FA have been found that have shown rare properties such as antiviral, antidiabetic, anti-helmintic, anti-inflammatory, anti-psoriatic, anti-ischemic, and anti-infective activities. In addition, FA have been found as potential regulators of lipid metabolism, as well as agents for the treatment of acute neurological disorders, as well as in the treatment of atherosclerosis and multiple sclerosis. For 36 FA, 3D graphs are presented, which demonstrate their predicted and calculated activities.
... 3.1). Линейные пептиды практически не проявляют токсических свойств, они в 100 раз менее токсичны, чем их циклические эквиваленты [Namikoshi, Rinehart, 1996]. ...
... Известно около 10 вариантов нодуларинов, среди которых наиболее распространен нодуларин-R. Как и микроцистины, нодуларины проявляют гепатотоксичность, ингибируя протеинфосфатазы 1 и 2А, и обладают канцерогенными свойствами [Namikoshi, Rinehart, 1996]. ...
Книга посвящена цианобактериям, древнейшим обитателям нашей планеты. Отличаясь особой жизнестойкостью, они существуют во всех регионах Земли при самых разных климатических условиях. Цианобактерии играют значительную роль в экологии биосферы, морей, океанов, иных водоемов, в сельскохозяйственной экологии, в геоэкологии и др. В книге обобщены материалы о строении
и метаболизме цианобактерий, их систематике и методах идентификации. Дана характеристика цианотоксинов и процессов их образования, их распространения в природных экосистемах, их роли в патологии человека и животных. Рассмотрены клинические данные острых и хронических заболеваний, вызванных токсичными метаболитами цианобактерий. Особое внимание уделено образованию
цианобактериями метаболитов, которые могут быть использованы в народном хозяйстве, для фармацевтических целей, как продукты питания человека и животных, в целях биоремедиации. Рассмотрены условия, которые способствуют развитию цианобактерий в водной среде и почвах, особенности воздействия их интенсивного размножения на окружающую среду. Приведены методы регуляции их развития, способы очистки воды как от самих цианобактерий, так и от их метаболитов. В книге подчеркивается ограниченность существующих пред-
ставлений о цианобактериях и их метаболитах. Формулируются те направления исследований, результаты которых способствовали бы положительному влиянию
цианобактерий на окружающую среду, применению их метаболитов в различных областях, в том числе для целей здравоохранения. Книга рассчитана на экологов и специалистов иных дисциплин, интересующихся цианобактериями.
... In invertebrates, most of the MNPs are microbe-driven and are a result of the symbiotic relationship between an invertebrate host and the microbial endosymbionts (Jiménez 2018). For example, cyanobacteria build many symbiotic relationships providing important bioactive compounds to the marine invertebrate hosts (Namikoshi and Rinehart 1996). ...
... These photosynthetic prokaryotes have been used as a food source rich in vitamins and proteins (Singh et al. 2005). Among many nutritious compounds identified in various cyanobacterial species, there are also pigments (e.g., carotenoids and chlorophyll) (Encarnação et al. 2015;Singh et al. 2005), minerals (Kamennaya et al. 2012) and, in some cases, toxins including hepatotoxins (i.e., microcystins and nodularins) and neurotoxins (i.e., anatoxins and saxitoxins) (Namikoshi and Rinehart 1996). Especially rich in bioactive compounds is marine species Lyngbya majuscule producing polyketides, lipopeptides and toxin such as apratoxin A that shows potent anticancer activity (Luesch et al. 2001;Singh et al. 2005). ...
Organisms exposed to diverse environmental conditions have developed mechanisms that enable them to adjust, adapt and survive. Understanding the adaptation strategies employed by different species will allow us to better comprehend and predict future biodiversity alterations under changing climate conditions. Cyanobacteria are prokaryotes found in various aquatic habitats, including terrestrial, as well as freshwater and saltwater systems. The aim of this study is to portray the diversity of habitats occupied by cyanobacteria and the molecular mechanisms employed by cyanobacterial species in response to exposure to, often extreme, abiotic stressors such as elevated water temperatures and light stress. Specifically, the focus of this review is to summarise the underlining mechanisms utilised by cyanobacteria allowing for their survival over billions of years. The climate changes that have been occurring over the past few decades in the environment have resulted in global warming, increased solar radiation and hypersalinity, and are predicted to continue rising in the future. Increased environmental pressure on marine cyanobacteria and other organisms is especially happening due to the prolonged and irregular periods of warm sea temperature, so-called marine heatwaves (MHWs). These periods of MHW are becoming more frequent and are putting additional pressure on marine organisms and diverse ecosystems. Many organisms adjust by changing the profile of genes expressed and performing complex cellular changes in response to stress. Understanding the consequences of elevated temperatures, hypersalinity and the impact of damaging ultraviolet radiation is not completely clear in terms of the ability of cyanobacteria to adapt/acclimatise. Under heat stress, changes in gene regulations in cyanobacteria affect the expression of different genes such as the one encoding molecular chaperones, photosynthetic and oxidative stress-related genes. An overview of various molecular mechanisms is discussed here, as well as the ability of cyanobacteria to endure thermal and light stress conditions.
... Bio-adsorbent material is mainly composed of carbon atomic and its structure is characterized by complexity and high porosity. It is produced from coconut shell, peat, soft and hard wood and olive pits, and other agricultural wastes [4]. ...
... The effect of initial concentration on equilibrium adsorption capacity was studied at pH 11.5, it was observed that the adsorption capacity of BS-SO3H gradually increase from 66 to 277 mg/g with increasing initial concentration of MB dye from 100 to 500 ppm ,while the adsorption capacity of CS-SO3H increase from 73 to 289 mg/g with increasing initial concentration of MB dye from 100 to 500 ppm as shown in Figures (3), (4).The increase in adsorption capacity is due to the greater concentration driving forces [8]. ...
... The possibility of the simultaneous presence of potentially toxic ingredients, such as microplastics, heavy metals, pesticides, cancerogenic compounds, EDC compounds and others, alongside those with a beneficial effect on the human body, should also be taken into account (Figure 3). Some species of algae, especially those from the group of cyanobacteria, produce highly poisonous toxins, especially for humans and animals, as well as competing algae species [143,144]. ...
Algae are currently used in many areas, including dietetics, pharmacy, cosmetology and to increase the nutritional value of food and animal feed due to their chemical composition. They are a source of extremely valuable molecules, including polyunsaturated fatty acids and pigments. Algae are also a valuable source of protein and almost all essential vitamins. They are rich in pigments such as chlorophyll, carotenoids and phycobiliproteins. These substances have a wide range of commercial applications. Due to its very intensive use, the demand for this plant raw material is constantly growing. Therefore, the methods of growing and harvesting algae are constantly improved in order to maximize the cultivation effect while minimizing costs and energy inputs. Future research should focus on improving algae cultivation and harvesting systems, with an emphasis on the possibility of genetic modifications that would allow even more efficient algae cultivation. This review summarizes methods of micro- and macroalgae cultivation, the chemical composition of selected algae species, which are important from the pharmaceutical, dietary and cosmetic points of view and therapeutic and dietary applications of compounds derived from different algae species. The key conclusion drawn from this article is that algae are an extremely valuable raw material, rich in numerous macro- and micronutrients necessary for humans, the acquisition of which is part of the currently important strategy of ecological policy for obtaining raw materials for various industries.
... [126] These compounds exhibit strong inhibitory activity against one or more serine proteases (including trypsin, plasmin, thrombin, elastase and chymotrypsin) in laboratory studies. [127][128][129] Interestingly, two novel compounds isolated from Microcystis sp. ...
Cancer is a group of illness that collectively are the second highest cause of death globally after cardiac disease. They can also affect the social, psychological, physical and economic well-being of individuals, families and societies. Novel drug discovery for new cancer chemotherapeutics is a lengthy, complex, and costly process. Cancer drugs that are currently in clinical use have several drawbacks, including serious undesirable side-effects and the development of resistance to anticancer drugs. Thus, the development of novel effective and low toxicity cancer drugs is a priority for medical science. In recent decades, natural products-derived cancer drug discovery has become a promising avenue for drug development and an increasing number of studies have been published. Cyanobacteria have potential as a source for novel drug discovery. Cyanobacterial bioactive metabolites have a large diversity of chemical structures, modes of action and therapeutic targets. Multiple cyanobacteria-derived compounds have successfully reached clinical trials, and some have already been approved by regulatory authorities including the FDA as anticancer drugs. This review highlights the therapeutic potential of cyanobacteria in cancer drug discovery and summarizes the cyanobacterial compounds already used as cancer chemotherapies. The review aims to highlight cyanobacteria as sources of potential new drugs and focus future research on this field.
... EPS also exhibit inhibitory actions against tumor growth (in vivo) and antiproliferative activity in cancer cell lines (in vitro) (Namikoshi & Rinehart, 1996;Yim, Son, Pyo, & Lee, 2005). The main mechanism of antitumor activity of the EPS is a reinforcement of immune system induced by the EPS (Zhou et al., 2004). ...
... NO is a free radical produced by phagocytes and plays a role in the immune system. In addition, other study also justified that SPs from cyanobacteria can promote immune system by triggering the cell and humor stimulation (Namikoshi and Rinehart, 1996). ...
... 257 Microalgae are enriched with high omega-3 polyunsaturated fatty acids (PUFAs) such as DHA and EPA which stimulate innate immune system, bile secretion, antioxidant activity, anti-inflammatory response and prevent liver lipid accumulation. [258][259][260] Many studies have reported that the liver is a complex immunological organ with different functions including metabolic activity, nutrient storage, and detoxification. 261 The liver contains a variety of tissue-resident lymphocytes. ...
Utilising novel ingredients in aquafeeds is necessary for the continued expansion and intensification of aquaculture production. Microalgae are utilised widely in aquaculture for a variety of purposes; as live feed for fish and shellfish larvae and juveniles, for the production of algae-based meals and oils to replace marine derived raw materials in aquafeeds, and for the production of astaxanthin, the carotenoid that gives salmon flesh its characteristic reddish colour. Notably, long-chain polyunsaturated fatty acids, amino acids, proteins, fibres, antioxidant pigments, vitamins and minerals are among the compounds in microalgae with great biological value. A growing collection of experimental data has demonstrated that these substances are crucial for increasing larval survival and enhancing the growth and well-being of fish and shellfish. In this review, the processing of microalgae utilised as aquafeed ingredient, the health promoting compounds in microalgae and their role in growth, immunity and disease resistance of fish and shellfish are described and discussed. Simultaneously , major hurdles in the commercial use of microalgae in aquafeed, and future research and development perspectives are all critically discussed.
... Some cyanobacteria have been recognized for the toxins they produce, which are capable of causing severe intoxications in humans and animals (Dittmann and Wiegand, 2006). One of the most prominent groups of such toxins is the microcystins, a group of phosphatase inhibitors, which are problematic when they enter drinking water supplies during dense cyanobacterial blooms (Namikoshi and Rinehart, 1996). The diverse cyanobacterial secondary metabolites are products of different biosynthetic machineries such as non-ribosomal peptide synthetases (NRPS) and polyketide synthases (PKS), but there are also peptides that are ribosomally synthesized and posttranslationally modified, the so called ribosomally synthetized and post-translationally modified peptides (RiPP) (Kehr et al., 2011;Li and Rebuffat, 2020). ...
The suomilide and the banyasides are highly modified and functionalized non-ribosomal peptides produced by cyanobacteria of the order Nostocales. These compound classes share several substructures, including a complex azabicyclononane core, which was previously assumed to be derived from the amino acid tyrosine. In our study we were able to isolate and determine the structures of four suomilides, named suomilide B – E (1–4). The compounds differ from the previously isolated suomilide A by the functionalization of the glycosyl group. Compounds 1–4 were assayed for anti-proliferative, anti-biofilm and anti-bacterial activities, but no significant activity was detected. The sequenced genome of the producer organism Nostoc sp. KVJ20 enabled us to propose a biosynthetic gene cluster for suomilides. Our findings indicated that the azabicyclononane core of the suomilides is derived from prephenate and is most likely incorporated by a proline specific non-ribosomal peptide synthetase-unit.
... The structure of this peptide was initially elucidated by two-dimensional nuclear magnetic resonance (2D-NMR) during the screening of metabolites from Microcystis aeruginosa, which marked the discovery of a new class of peptides possessing serine protease inhibitory activity [18,19]. Aeruginosin is characterized by the occupation of the 2-carboxy-6-hydroxy-octahydroindole (Choi) moiety at the central position in the tetrapeptide, while other positions are occupied by a single variable residue of congeners [20]. Aeruginosins are a family of chemo-diverse peptides that have been shown to inhibit serine protease in vitro [21]. ...
Aeruginosins, a family of nonribosomal linear tetrapeptides discovered from cyanobacteria and sponges, exhibit in vitro inhibitory activity on various types of serine proteases. This family is characterized by the existence of the 2-carboxy-6-hydroxy-octahydroindole (Choi) moiety occupied at the central position of the tetrapeptide. Aeruginosins have attracted much attention due to their special structures and unique bioactivities. Although many studies on aeruginosins have been published, there has not yet been a comprehensive review that summarizes the diverse research ranging from biogenesis, structural characterization and biosynthesis to bioactivity. In this review, we provide an overview of the source, chemical structure as well as spectrum of bioactivities of aeruginosins. Furthermore, possible opportunities for future research and development of aeruginosins were discussed.
... Cyanobacteria, previously known as blue-green algae, are morphologically various divisions of prokaryotic and photosynthetic organisms that flourish in varied types of habitats. Most species of cyanobacteria are free-living in freshwater, marine, or terrestrial habitats and are symbioses with other plants and lichens [46]. Algal organisms exhibited a wide diverse of cell sizes. ...
Currently, algae arouse a growing interest in the pharmaceutical and cosmetic area due to the fact that they have a great diversity of bioactive compounds with the potential for pharmacological and nutraceutical applications. Due to lifestyle modifications brought on by rapid urbanization, diabetes mellitus, a metabolic illness, is the third largest cause of death globally. The hunt for an efficient natural-based antidiabetic therapy is crucial to battling diabetes and the associated consequences due to the unfavorable side effects of currently available antidiabetic medications. Finding the possible advantages of algae for the control of diabetes is crucial for the creation of natural drugs. Many of algae's metabolic processes produce bioactive secondary metabolites, which give algae their diverse chemical and biological features. Numerous studies have demonstrated the antioxidant and antidiabetic benefits of algae, mostly by blocking carbohydrate hydrolyzing enzyme activity, such as α-amylase and α-glucosidase. Additionally, bioactive components from algae can lessen diabetic symptoms in vivo. Therefore, the current review concentrates on the role of various secondary bioactive substances found naturally in algae and their potential as antioxidants and antidiabetic materials, as well as the urgent need to apply these substances in the pharmaceutical industry.
... Cyanobacteria synthesized a large number of small peptides termed as non-ribosomal peptides [33]. e non-ribosomal polypeptides are approximately 50 amino acids long, and catalyzed by non-ribosomal peptide synthetases (NRPSs). ...
The occurrence of cyanobacterial blooms in nutrients enriched aquatic ecosystems is a widespread phenomenon. Cyanobacterial blooms synthesized several bioactive compounds, and cyanotoxin is among one of them. The most commonly reported cyanotoxin are Nodularin, Microcystins Anatoxin‐a, Saxitoxins, and Cylindrospermopsin. Biochemically, cyanotoxins are polyketides, alkaloids, nonribosomal peptides, potent toxins, and trypsin inhibitors. Pharmaceutically and neutraceutically these are significant, and exhibits, a diverse range of bioactivity, mainly antiviral, antibacterial, antitumor, anticancerous, antifungal, etc. Several oligopeptides are synthesized through nonribosomal peptide synthetase (NRPSs) in prokaryotes and lower eukaryotes. Cyanobacterial bioactive compounds are not utilized in growth and developments but are a promising source for the novel compounds. Nutrient composition especially nitrogen and phosphorus significantly influences types of bioactive compounds. The common cyanotoxin frequently occurred in cyanobacterial blooms is Microcystin, and is encoded by mcy gene cluster in freshwater and brackish water ecosystems. There are several methods used for purification and characterizations of the bioactive compounds from blooms forming cyanobacterial such as HPLC, UPLC, LC‐MS‐MS, and MALDI‐TOF‐MS. This review mainly focused on novel bioactive compounds obtained from cyanobacteria.
... Such an effect has been demonstrated on several viruses, including herpes simplex virus (HSV), HIV, respiratory syncytial virus (RSV), influenza, measles, mumps, and polio, and it is associated with the anionic nature of the polymers, which blocks internalization into the host (Ahmadi et al. 2015). In addition, sulfated polysaccharides have immunostimulant, antiadhesive, antioxidant, anticancer, anticoagulant, antiarteriosclerosis, and hypolipidemic properties (Chen et al. 2010;Dvir et al. 2009;Gardeva et al. 2009;Guzman-Murillo and Ascencio 2000;Jiménez-Escrig et al. 2011;Khan et al. 2005;Namikoshi et al. 1996). ...
... The increasing tendency of microbial infections, and the rapid emergence of antibiotics against multidrug-resistant organisms have directed attention towards the natural sources of antimicrobial compounds (Chauhan et al., 2014;Pandy, 2015). Quercitin, phycocyanin pigment, polysaccharide (Abdo et al., 2012), amino acids, terpenoids, tannins, steroids, phenolic compounds, halogenated ketones, alkenes, and cyclic polysulfides (Kini et al., 2020) are bioactive compounds produced by various cyanobacterial species (Namikoshi et al., 1996). ...
Cyanophyceae (blue-green algae) is a group of prokaryotic microorganisms. The antioxidative phyto-chemical constituents present in them have received attention for their role in the prevention of human diseases. This study mainly concentrates on the presence of phytochemical constituents in the methanolic extract of Gloeothece rupestris and the antioxidant and antimicrobial activity of the extracted constituents. The qualitative phytochemical analysis showed the presence of alkaloids, carbohydrates, flavonoids, glycosides, fixed oils and fats, and phytosterols. The methanol extract was used at different concentrations to estimate the antioxidant potential by 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity. The in vitro antimicrobial activity was evaluated against various human pathogenic bacteria, such as Staphylococcus au-reus, Staphylococcus epidermidis, Escherichia coli, Klebsiella pneumonia, Proteus vulgaris, Pseudomonas aeruginosa, and some fungal pathogens, such as Aspergillus niger, Aspergillus flavus, and Candida albicans. The extract showed much more effective antibacterial activity as compared with the antifungal activity. The study concluded that Gloeothece rupestris (Lyngbye) Bornet possesses unique bioactive compounds, potential antioxidant and antimicrobial properties, which can be exploited for industrial applications.
... This is commonly imputed to low nutritional value, due to a lack of poly-unsaturated fatty acids (PUFAs) and/or sterols (DeMott & Müller-Navarra 1997;Ravet et al., 2003), in addition to their toxicity . A major concern regarding the increasing occurrence of harmful algal blooms, cyanobacteria are renowned for their exceptional bioactivity and toxin production (Namikoshi & Rinehart, 1996;Huang & Zimba, 2019). Over time, cyanobacteria have evolved a variety of secondary metabolites and bioactive compounds (Welker & Von Döhren, 2006;Agha & Quesada, 2014), some of which can cause adverse effects to other organisms (including humans) and have thus been referred to as cyanotoxins (Carmichael, 1992;Chorus, 2012). ...
Cyanobacteria periodically dominate phytoplankton composition in lakes, and produce a wide array of toxic secondary metabolites. Blooms of cyanobacteria often coincide with infections of zooplankton by microparasites (such as Metschnikowia bicuspidata , a parasitic yeast of Daphnia ), and prior research has shown that cyanobacteria-based diets could mitigate fungal infections of the host. Here, we tested whether cyanotoxins could exert detrimental effects against free-living parasite stages: we inoculated two genotypes of the host Daphnia galeata × longispina with fungal spores, which were previously exposed to cyanobacterial extracts or to a placebo solution. Additionally, to test for interactive effects of cyanotoxins through environmental exposure and host consumption, Daphnia from each treatment were fed using either green algae or the same cyanobacterium. Exposing spores to cyanobacterial extracts did not reduce their infectivity; instead, parasite infectivity was increased, but only on one host genotype. The effect of host diet on parasite growth was also host-genotype dependent, with only one Daphnia genotype showing impaired spore production under a toxic diet. Our results suggest that dissolved cyanobacterial compounds released during blooms may not exert any detrimental effect on fungal spore banks, but likely influence transmission of the parasite when incorporated as part of the host’s diet.
... A wide array of enzymes is present in cyanobacteria that are liable for tailoring, oxidations, methylation, and other modifications [118], resulting in naturally and chemically varied products like depsipeptides [119], glicomacrolides [120], linear peptides [121], swinholides [120], cyclic peptides [122], fatty acid amides [123], and cyclic depsipeptides [124]. Scientists have been studying secondary metabolites from cyanobacteria for the past two centuries because of two main factors (i) multiple secondary metabolites derived from cyanobacteria used for therapeutic purposes potentially (ii) adverse effects of the toxin on humans and animals, which are produced by cyanobacteria present in freshwater ecosystems [125,126]. Mycosporine and scytonemin like amino acids are produced by some species of cyanobacteria which are useful for detecting or combating UV radiation effects [127]. ...
Microalgae and cyanobacteria have sparked a lot of interest due to their potential in various industries like biorefineries, biopharmaceuticals, food supplements, nutraceuticals, and other high-value products. Polysaccharides, vitamins, proteins, enzymes, and steroids are valuable products isolated from microalgae and cyanobacteria and potentially used in health and biomedical applications. Bioactive compounds derived from microalgae and cyanobacteria exhibit various pharmaceutical properties like antibacterial, anticancer, antiviral, antialgal, and antioxidant. From the properties listed above, the research for novel antibiotics has become particularly appropriate. In addition, the possible emergence of resistance against pathogens, as well as the potential decline in antibiotic efficacy, has prompted researchers to look for a new source of antibiotics. Microalgae and cyanobacteria have indicated a great and unexplored potential among these sources. For this reason, microalgae and cyanobacteria have been highlighted for their efficiency in different industrial sectors, as well as for their potential uses in the betterment of human and environmental health. This review gives an overview of bioactive compounds and metabolites with several biological properties isolated from microalgae and cyanobacteria for treating different animal and human diseases.
... Cyclic depsipeptides ichthyopeptins A and B isolated from Microcystis ichthyoblabe are active against influenza A virus (Zainuddin et al. 2007). Anabaenopeptin B a cyclic hexapeptide isolated from Anabaena flos-aquae showed antiviral activity, while several species of Microcystis aeruginosa, Anabaena, and Oscillatoria and Nodularia spumigena produced antiviral compounds (Namikoshi and Rinehart 1996). Antiviral compounds and its source are presented in Table 6.4. ...
Cyanobacteria the least explored microorganisms have lots of potential for synthesis and production of numerous antimicrobial secondary metabolites. As they are ubiquitous in distribution and present in all possible habitats, cyanobacteria have developed several mechanisms to survive in various extreme habitats. Also, they are compatible biocatalysts, and they can be used in the field of “white biotechnology” for increasing the sustainable manufacture of nutraceutical and pharmaceutical compounds as novel drugs and also as clean energy sources such as biodiesel and hydrogen. Cyanobacteria are known as a mother of wide categories of secondary metabolites with different biological activities, i.e., antibacterial, antitumoral, antiviral, antifungal, antialgal, antimalarial, anti-inflammatory, and anticancer properties. In this chapter, we try to uncover the application of various metabolites like phytols, free fatty acids, exopolysaccharides, phenolics, terpenoids, phytoene, sterols, carotenoids, MAAs, scytonemin, phytohormones, cyanotoxins, biocides (algicides, fungicides, bactericides, and insecticides), etc. and its various applications.
... These microbes release various kinds of biologically active substances, which promote plant growth and help plants to fight against various biotic or abiotic stresses (Mendes et al. 2013). Cyanobacteria also produce phytohormones (auxins, gibberellins, cytokinins, abscisic acid), amino acids (serine, arginine, glycine, aspartic acid, threonine, glutamic acid), vitamin B12, extra-and intra-cellular polysaccharides (xylose, galactose, fructose) as well as toxic compounds with pharmacological, immune-suppressive capacities (Namikoshi and Rainehart 1996;Sergeeva et al. 2002). Certain cyanobacteria also release signalling molecules, known as elicitors. ...
Cyanobacteria are unique group of photosynthetic gram-negative prokaryotes. They are precious bio-resource option for sustainable development of agriculture. Cyanobacteria belong to blue green algae, and they can survive under minimum presence of light, carbon dioxide and water. Apart from their primary role in fixing atmospheric nitrogen and improving soil nutrient status, they can deliver multifaceted but unique tasks like production of plant growth promoting bioactive molecules, bioremediation of heavy metals, decomposition of organic residues, generation of high valued biological substances, etc. They also have the potential to act as bio-control agents against several plant pathogenic bacteria or fungi. Further, they can help to curb CO2 loading in atmosphere by enhancing soil methane sink through methanotrophic diversity. Cyanobacteria also exude extracellular polysaccharides that increase activity of nutrient-liberating enzymes and induce growth promotion of other beneficial soil-microbes. They help to improve structural stability of soil by holding soil particles together, particularly when their biomass get incorporated into soil. Cyanobacteria, by forming consortia with other plant growth promoting rhizobacteria, increase plant growth and also enhance tolerance of plants to various environmental stresses. For these reasons, cyanobacteria are considered as a key factor towards the betterment of soil health and ecological resilience.
... As expected from the mass range, the most abundant class of compounds in the active extract is represented by peptides, comprising cyclic, hybrid peptides, and depsipeptides. Six clusters revealed the presence of peptide cyanotoxins in the extract, which account for its toxicity (Table 1) [17], two belong to micropeptins (MP-88B [18], MP-T1 [19]), and other two were dereplicated as anabaenopeptin C [20] and aeruginopeptin 228B [21]. Nodes in the cyanotoxin clusters, which could not be associated to any known compound, indicated the presence of new molecular entities, structurally related to the cyanotoxins, which require further studies for their identification. ...
Cyanobacteria are ubiquitous photosynthetic microorganisms considered as important contributors to the formation of Earth’s atmosphere and to the process of nitrogen fixation. However, they are also frequently associated with toxic blooms, named cyanobacterial harmful algal blooms (cyanoHABs). This paper reports on an unusual out-of-season cyanoHAB and its dynamics during the COVID-19 pandemic, in Lake Avernus, South Italy. Fast detection strategy (FDS) was used to assess this phenomenon, through the integration of satellite imagery and biomolecular investigation of the environmental samples. Data obtained unveiled a widespread Microcystis sp. bloom in February 2020 (i.e., winter season in Italy), which completely disappeared at the end of the following COVID-19 lockdown, when almost all urban activities were suspended. Due to potential harmfulness of cyanoHABs, crude extracts from the “winter bloom” were evaluated for their cytotoxicity in two different human cell lines, namely normal dermal fibroblasts (NHDF) and breast adenocarcinoma cells (MCF-7). The chloroform extract was shown to exert the highest cytotoxic activity, which has been correlated to the presence of cyanotoxins, i.e., microcystins, micropeptins, anabaenopeptins, and aeruginopeptins, detected by molecular networking analysis of liquid chromatography tandem mass spectrometry (LC-MS/MS) data
... Cyanobacteria is prominent in producing variety of compounds with a wide range of bioactivities. The well-studied compounds of Cyanobacteria origin include: microcystins, anatoxins, micropeptins, and microviridin (Namikoshi and Rinehart, 1996). These small bioactive compounds are prolific in the activity against cellular enzymes and thus interfering in signaling pathways. ...
Endophytes play a vital role in the survival of host plants by aiding defense responses by producing bioactive compounds similar to their host plants. To fulfill the ever-increasing demand for herbal drugs to cure human ailments, researchers are searching for the various sources of bioactive compounds besides medicinal plants. It was reported that in the international market, the demand of 3 kg per year of vinca alkaloids (1.5×106 kg dry leaves are required) to develop powerful plant-derived anticancer drugs. In this regard, this review aims to highlight the endophytes residing in Catharanthus roseus (family: Apocynaceae), capable of synthesizing indole alkaloids, vinblastine, vincristine, vindoline, vinflunine, vincamine, ajmalicine, ajmaline, serpentine, and reserpine used to control cancer, diabetes, malaria, vascular dementia, cardiac diseases, etc. In the search to fulfill the demand, there is urgent need to develop an efficient method of isolation, identification of endophytes, and the down-streaming process for more efficient and sustainable production of vinca alkaloids from endophytic fungus for the cancer treatment products. Microbial fermentation by optimizing media composition, precursors, inducers, and the metabolic bypass inhibitors would be a promising method in the production of vinca alkaloids at industrial scale. Furthermore, different biotechnological strategies such as gene cloning, gene transformation, and mutations can widely be used on endophytic fungi and bacteria in order to increase the productivity of the vinca alkaloids. Thus, advancements in science and technology have increased the extraction yield from vinca alkaloid producing endophytes, thereby improving the overall efficiency of alkaloid production.
... Cyanobacteria is prominent in producing variety of compounds with a wide range of bioactivities. The well-studied compounds of Cyanobacteria origin include: microcystins, anatoxins, micropeptins, and microviridin (Namikoshi and Rinehart, 1996). These small bioactive compounds are prolific in the activity against cellular enzymes and thus interfering in signaling pathways. ...
Cyanobacteria, popularly known as blue-green algae, are some of the early inhabitants of Earth. These are photosynthetic organisms owing to the presence of plastids. These prokaryotic organisms produce various bioactive compounds using a nonribosomal peptide synthetase (NRPS) and polyketide synthase pathway (PKS). The antimicrobial properties have been reported for some of these compounds. In this chapter, we have discussed various biosynthetic pathways for the production of these molecules. The use of these compounds as nutraceuticals and antibiotics are enumerated. Antimicrobial and multidrug resistance is one of the significant challenges in disease management. We have suggested that Cyanobacteria-derived compounds or antibiotics are promising and can be used instead of conventional antibiotics. Further, we comprehended various chemical diversity of the secondary metabolites obtained from Cyanobacteria and its positioning as a new class of therapeutics.
... Such an effect has been demonstrated on several viruses, including herpes simplex virus (HSV), HIV, respiratory syncytial virus (RSV), influenza, measles, mumps, and polio, and it is associated with the anionic nature of the polymers, which blocks internalization into the host (Ahmadi et al. 2015). In addition, sulfated polysaccharides have immunostimulant, antiadhesive, antioxidant, anticancer, anticoagulant, antiarteriosclerosis, and hypolipidemic properties (Chen et al. 2010;Dvir et al. 2009;Gardeva et al. 2009;Guzman-Murillo and Ascencio 2000;Jiménez-Escrig et al. 2011;Khan et al. 2005;Namikoshi et al. 1996). Among the most recurrent sulfated polysaccharides in literature are: ulvan and laminarin (mentioned above as dietary fiber), fucoidan carbohydrates mainly composed of L-fucose, which appears in brown seaweeds in amounts of around 2-10%, especially in the cell walls of seaweed species in the Fucaceae and Laminariaceae families. ...
Nutraceutical and functional foods are seen as those natural bioactive chemical compounds able to provide both health benefits to reduce the risk of chronic diseases and nutrition. This new group of products promises to be the solution to many health problems. Though both microalgae and seaweeds have been in the human diet for thousands of years, only in recent years with the new technological outcomes has the algal nutraceutical potential been reported. Algae could play an important role in the increasing the commercial value of the functional foods market. This chapter presents an overview of the main molecules that have been recovered from microalgae and seaweeds and their nutraceutical benefits and applications.
... In recent years, the research on the cyanobacterial bioactive compounds has intensified in the areas of cyanobacterial toxins and cyanobacterial metabolites (Dittmann & Wiegand, 2006;Eghtedari et al., 2021;Gademann & Portmann, 2008;LewisOscar et al., 2018;Liu et al., 2014;Namikoshi & Rinehart, 1996;Niedermeyer, 2015;Nowruzi et al., 2012;2013;2018a;2018b;Nowruzi & Blanco, 2019;Rajabpour et al., 2019;Swain et al., 2017;Yadav et al., 2011). They have evolved to produce such varied natural products due to factors but not limited to their versatile adaptability to inhabit diverse environments, variability of morphology and chemical defense against diverse macrograzers. ...
The recent Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), positive-sense RNA viruses, originated from Wuhan City in December 2019 and propagated widely globally. Hence, the disease caused by this virus has been declared as a global pandemic by the WHO. As of 18th February 2021, at least seven different vaccines across three platforms have been rolled out in countries and more than 200 additional vaccine candidates have been in development, of which more than 60 are at the stage of the clinical development. So far, Most of the approved vaccine manufacturers are Pfizer, AstraZeneca, and Serum Institute of India, which have been finalized by WHO. Synthetic drug-associated complications have evoked scientific attention for natural product-based drugs. There has been a surge in the antiviral compounds from natural resources along with some therapies. Cyanobacteria are the fruitful reservoir of many metabolites like sulfated polysaccharides and lectins that possess strong antiviral activities and immunity boosting effects. However, the research in this field has been relatively under-developed. The current research highlights important features of cyanobacterial antiviral biomaterials, benefits and drawbacks of cyanobacterial drugs, challenges, future perspectives as well as overview of drugs against COVID-19. In addition, we have described mutated variants and transmission rate of coronaviruses. The current research suggests that cyanobacterial species and their extracts have promising applications as potentially antiviral drug biomaterials against COVID-19.
Communicated by Ramaswamy H. Sarma
... To date, microalgae remain largely unexplored and represent a unique opportunity to discover novel metabolites and produce metabolites at a lower cost. As a group, the microalgae in its wider sense (including cyanobacteria), are known to produce a remarkable diversity of biologically active metabolites [14][15][16]. Despite nearly 18,500 new compounds isolated from marine sources between 1965 and 2006, it is estimated that about 97% of all existing marine compounds have not yet been isolated, and have therefore not undergone any chemical or biological characterization [17][18][19]. ...
The intensive use of synthetic herbicides over the past 50 years has led to a number of deleterous impacts on the terrestrial and aquatic environment and is a serious challenge to the ability to sustain agricultural production into the future. In order to remedy this problem, the use of biocontrols is rapidly accelerating and initiating the transition of the agricultural system into an agroecological system. Microalgae (in its wider sense, eukaryote and cyanobacteria) from marine and freshwater habitats are known to produce a diverse range of toxic or otherwise bioactive allelochemical metabolites for growth, communication and defense. Between the search for innovative active molecules and the development of new production processes at the dawn of biotechnology, microalgae have an immense potential in their contribution to biocontrol products. Microalgal organisms can be grown in mass cultures enabelling their manipulation for optimal production of bioactive substances, giving them a significant advantage over terrestrial plants in exploring their effectiveness. In this review we will present the structural diversity of allelochemical compounds and their role for microalgae, the competitive advantages that these compounds provide to microalgae compared to competing species, as well as their potential as biological control agents and bioherbicides.
... Their high toxicity is determined by the presence of the unique Adda acid (3-amino-9-methoxy-2,6,8-thimethyl-10-phenyldeca-4,6-dienoic acid), which was detected only in cyanobacterial toxins (Harke et al., 2016), and a cyclic structure (Fig. 1). Linear peptides show almost no toxic properties; they are 100 times less toxic than their cyclic equivalents (Namikoshi and Rinehart, 1996) Potent toxins include saxitoxin and its analogs, collectively known as paralytic shellfish toxins (PSTs). They are a diverse group of heterocyclic compounds (Carmichael, 1997). ...
This review is devoted to analyzing the global occurrence of cyanobacteria in water ecosystems, the possible causes of this phenomenon, and its consequences. In recent decades, cyanobacteria have been rapidly expanding in waterbodies all over the world. This expansion is accompanied by water pollution with dangerous cyanotoxin metabolites that represents a significant threat to humans, animals, and the environment. Purifying water of cyanobacteria is a serious problem, because it is necessary to eliminate toxins and the unpleasant taste and odor of drinking water, as well as fight the biocorrosion caused by cyanobacterial fouling. Cyanobacterial blooms concern not only issues related to the water supply, but also to fishing, the recreational use of waterbodies, and tourism. Global warming and climate change, the increasing eutrophication of natural waters, and anthropogenic pollution, as well as the unique physiological characteristics of cyanobacteria and their ability to adapt to a variety of environmental conditions, including extreme environments, are among the main factors contributing to the expansion of cyanobacteria.
... The inhibition of the activity of proteolytic enzymes, such as chymotrypsin, trypsin, elastase, and thrombin, by cyanobacterial extracts has been frequently reported [36,37]. Inhibition of both elastase and trypsin was also assigned to peptides such as micropeptins, cyanopeptolins, microviridins, and banyasides [37][38][39][40][41][42]. The production of potent inhibitors has also been found in several cyanobacteria, like Microcystis, Planktothrix, Anabaena, Nostoc, Lyngbya, and Symploca [43][44][45]. ...
Microcystins (MCs) are cyanobacterial toxins and potent inhibitors of protein phosphatases 1 (PP1) and 2A (PP2A), which are involved in plant cytoskeleton (microtubules and F-actin) organization. Therefore, studies on the toxicity of cyanobacterial products on plant cells have so far been focused on MCs. In this study, we investigated the effects of extracts from 16 (4 MC-producing and 12 non-MC-producing) cyanobacterial strains from several habitats, on various enzymes (PP1, trypsin, elastase), on the plant cytoskeleton and H2O2 levels in Oryza sativa (rice) root cells. Seedling roots were treated for various time periods (1, 12, and 24 h) with aqueous cyanobacterial extracts and underwent either immunostaining for α-tubulin or staining of F-actin with fluorescent phalloidin. 2,7-dichlorofluorescein diacetate (DCF-DA) staining was performed for H2O2 imaging. The enzyme assays confirmed the bioactivity of the extracts of not only MC-rich (MC+), but also MC-devoid (MC−) extracts, which induced major time-dependent alterations on both components of the plant cytoskeleton. These findings suggest that a broad spectrum of bioactive cyanobacterial compounds, apart from MCs or other known cyanotoxins (such as cylindrospermopsin), can affect plants by disrupting the cytoskeleton.
... The inhibition of the activity of proteolytic enzymes, such as chymotrypsin, trypsin, elastase and thrombin, by cyanobacterial extracts has been frequently reported [33,34]. Inhibition of both elastase and trypsin was also assigned to peptides such as micropeptins, cyanopeptolins, microviridins, and banyasides [34][35][36][37][38][39]. The production of potent inhibitors has also been found in several cyanobacteria, like Microcystis, Planktothrix, Anabaena, Nostoc, Lyngbya, and Symploca [40][41][42]. ...
Microcystins (MCs) are cyanobacterial toxins and potent inhibitors of protein phosphatases 1 (PP1) and 2A (PP2A), which are involved in plant cytoskeleton (microtubules and F-actin) organization. Therefore, studies on the toxicity of cyanobacterial products on plant cells have so far being focused on MCs. In this study, we investigated the effects of extracts from 16 (4 MC-producing and 12 non-MC-producing) cyanobacterial strains from several habitats, on various enzymes (PP1, trypsin, elastase), on the plant cytoskeleton and H2O2 levels in Oryza sativa (rice) root cells. Seedling roots were treated for various time periods (1, 12 and 24h) with aqueous cyanobacterial extracts and underwent either immunostaining for α-tubulin or staining of F-actin with fluorescent phalloidin. DCF-DA staining was performed for H2O2 imaging. The enzyme assays confirmed the bioactivity of the extracts of not only MC-rich (MC+), but also MC-devoid (MC-) extracts, which induced major time-dependent alterations on both components of the plant cytoskeleton. These findings suggest that a broad spectrum of bioactive cyanobacterial compounds, apart from MCs or other known cyanotoxins (such as cylindrospermopsin), can affect plants by disrupting the cytoskeleton.
... Moreover, Cyanobacteria played a role in another major biological event, the spread of photosynthesis to eukaryotic lineages through an initial endosymbiosis termed "primary", followed by several higher-order endosymbioses (9). Finally, Cyanobacteria produce a large number of bioactive compounds (e.g., alkaloids, non-ribosomal peptides, polyketides), which make them promising for both biotechnological and biomedical applications (10)(11)(12). ...
Cyanobacteria form one of the most diversified phylum of Bacteria. They are important ecologically as primary producers, for Earth evolution and biotechnological applications. Yet, Cyanobacteria are notably difficult to purify and grow axenically, and most strains in culture collections contain heterotrophic bacteria that were likely associated to Cyanobacteria in the environment. Obtaining cyanobacterial DNA without contaminant sequences is thus a challenging and time-consuming task. Here, we deploy a metagenomic pipeline that enables the easy recovery of high-quality genomes from non-axenic cultures. We tested this pipeline on 17 cyanobacterial cultures from the BCCM/ULC public collection and generated novel genome sequences for 15 arctic or subarctic strains, of which 14 early-branching organisms that will be useful for cyanobacterial phylogenomics. In parallel, we managed to assemble 31 co-cultivated bacteria from the same cultures and showed that they mostly belong to Bacteroidetes and Proteobacteria, some of them being very closely related in spite of geographically distant sampling sites.
Importance
Complete genomes of cold-adapted Cyanobacteria are underrepresented in databases, due to the difficulty to grow them axenically. In this work, we report the genome sequencing of 12 (sub)arctic and 3 temperate Cyanobacteria, along with 21 Proteobacteria and 5 Bacteroidetes recovered from their microbiome. Following the use of a state-of-the-art metagenomic pipeline, 12 of our new cyanobacterial genome assemblies are of high-quality, which indicates that even non-axenic cultures can yield complete genomes suitable for phylogenomics and comparative genomics. From a methodological point of view, we investigate the fate of SSU rRNA (16S) genes during metagenomic binning and observe that multi-copy rRNA operons are lost because of higher sequencing coverage and divergent tetranucleotide frequencies. Moreover, we devised a measure of genomic identity to compare metagenomic bins of different completeness, which allowed us to show that Cyanobacteria-associated bacteria can be highly related in spite of considerable distance between collection points.
... Keeping in mind its evolutionary significance, phytochemical and pharmacological studies of this group may lead to the discovery of certain novel metabolites having unique therapeutic potential. Cyanobacteria, are arguably a group of the photosynthetic oxygen-evolving prokaryotes that originated 2.8 billion years ago (Schopf and Packer, 1987;Schwartzman et al., 2008), could have faced many environmental stresses during evolution, have been perceived as the novel source of antibiotic, antifungal, anticancer, antihelminthic, enzyme inhibitors, photosynthesis inhibitors, hemagglutinins, antiviral, anticoagulant, antiinflammatory, antimalarial, antiprotozoal, antituberculosis, and immunosuppressive activities that show prodigious bioactive potential for drug targeting (Burja et al., 2001;Tan, 2007Tan, , 2010Tan, , 2013Nunnery et al., 2010;Mayer et al., 2011;Gerwick and Moore, 2012;Namikoshi and Rinehart, 1996;Jaiswal et al., 2008, Sivonen andPrasanna et al., 2010;Vestola et al., 2014;Volk and Furkert, 2006;Bhatnagar and Kim, 2010;Pearson et al., 2010;Jones et al., 2011). Curacin A, a mixed polyketide, nonribosomal peptide possessing antimitotic and antiproliferative activity, was isolated from L. majuscula (Geders et al., 2007). ...
Cancer is a multifaceted disease with different hallmarks. The development procedure of anticancer drugs needs different screening methods and disease models to examine the basic mechanism of action of natural products. At present, more than 60% of anticancer drugs are natural products which are either isolates of plants or their derivatives, indicating the opportunity for new drug development from natural product. The mode of action and targets of different compounds are generally different, leading to a challenge for researcher to elucidate the action and mechanism appropriately. For an anticancer drug development, several experimental procedures are required such as extraction, fractionation, purification, identification and finally evaluation. This procedure is completed through different experimental models and assays such as biochemical characterization, antioxidant assay, anticancer assay, ROS assay, apoptosis assay, cell migration assay, pharmacological assays, computer-based evaluation, etc. The screening and development of anticancer drugs are well discussed in this chapter.
... Keeping in mind its evolutionary significance, phytochemical and pharmacological studies of this group may lead to the discovery of certain novel metabolites having unique therapeutic potential. Cyanobacteria, are arguably a group of the photosynthetic oxygen-evolving prokaryotes that originated 2.8 billion years ago (Schopf and Packer, 1987;Schwartzman et al., 2008), could have faced many environmental stresses during evolution, have been perceived as the novel source of antibiotic, antifungal, anticancer, antihelminthic, enzyme inhibitors, photosynthesis inhibitors, hemagglutinins, antiviral, anticoagulant, antiinflammatory, antimalarial, antiprotozoal, antituberculosis, and immunosuppressive activities that show prodigious bioactive potential for drug targeting (Burja et al., 2001;Tan, 2007Tan, , 2010Tan, , 2013Nunnery et al., 2010;Mayer et al., 2011;Gerwick and Moore, 2012;Namikoshi and Rinehart, 1996;Jaiswal et al., 2008, Sivonen andPrasanna et al., 2010;Vestola et al., 2014;Volk and Furkert, 2006;Bhatnagar and Kim, 2010;Pearson et al., 2010;Jones et al., 2011). Curacin A, a mixed polyketide, nonribosomal peptide possessing antimitotic and antiproliferative activity, was isolated from L. majuscula (Geders et al., 2007). ...
... Cette eutrophisation provoque souvent le développement massif des cyanobactéries potentiellement toxiques, qui constituent une source de contamination qui menace la santé publique. Les cyanobactéries peuvent avoir un grand nombre de métabolites secondaires qui sont des composés non-essentiels pour leur croissance et leur reproduction ; ceux-ci incluent des peptides, des macrolides et des glycosides [2,3]. De nombreux travaux ont montré que ces composés possèdent diverses activités biologiques : antivirales, antifongiques [2], cytotoxiques [4], inhibitrices de protéines phosphatases [5], antinéoplasiques [6] et allélopathiques [7]. ...
En raison de l’urbanisation, du développement industriel et agricole, le taux des éléments nutritifs (azote et phosphore) augmente considérablement dans les écosystèmes aquatiques. Cela conduit de plus en plus fréquemment à une eutrophisation de l’eau et à la prolifération des cyanobactéries, entraînant un déséquilibre dans la dynamique des écosystèmes qui peuvent être plus toxiques en produisant des cyanotoxines, des molécules toxiques pour la santé publique et environnementale. L’objet de ce présent article est de faire la synthèse des travaux actuellement publiés sur les intoxications par les cyanobactéries et leurs toxines en Algérie et de par le monde. Une revue de littérature nous a permis de comprendre l’importance d’une synthèse des travaux afin de faciliter la compréhension des phénomènes liés aux intoxications aiguës, chroniques et subchroniques. Les voies d’intoxication directes, via l’eau, et indirectes, via les animaux et les plantes, sont recensées. Les cas algériens révélant une telle intoxication chez l’homme ou les animaux sont également listés.
... NO is a free radical produced by phagocytes and plays a role in the immune system. In addition, other study also justified that SPs from cyanobacteria can promote immune system by triggering the cell and humor stimulation (Namikoshi and Rinehart, 1996). ...
The skin is the first line of defense against pathogen and other environmental pollutant. The body is constantly exposed to reactive oxygen species (ROS) that stimulates inflammatory process in the skin. Many studies have linked ROS to various inflammatory skin diseases. Patients with skin diseases face various challenges with inefficient and inappropriate treatment in managing skin diseases. Overproduction of ROS in the body will result in oxidative stress which will lead to various cellular damage and alter normal cell function. Multiple signaling pathways are seen to have significant effects during ROS-mediated oxidative stress. In this review, microalgae have been selected as a source of natural-derived antioxidant to combat inflammatory skin diseases that are prominent in today’s society. Several studies have demonstrated that bioactive compounds isolated from microalgae have anti-inflammation and anti-oxidative properties that can help remedy various skin diseases. These compounds are able to inhibit production of pro-inflammatory cytokines and reduce the expression of inflammatory genes. Bioactive compounds from microalgae work in action by altering enzyme activities, regulating cellular activities, targeting major signaling pathways related to inflammation.
... Recent research suggests that eutrophication and climate change are two processes they may promote the proliferation and expansion of harmful cyanobacterial blooms in freshwater, estuarine, and marine ecosystems. These microorganisms are known to biosynthesize a wide range of chemical classes of secondary metabolites such as peptides, macrolides, and glycosides (Patterson et al., 1994;Namikoshi and Rinehart, 1996) possessing a number of bioactivities: antiviral (Patterson et al. 1993(Patterson et al. , 1994, antifungal (Patterson et al., 1994), cytotoxic (Patterson et al., 1991), enzymatic inhibitor (Honkanen et al., 1995), antineoplastic (Moore, 1996), and allelopathic (Pushparaj et al., 1998). However, some of these cyanobacterial secondary metabolites encompass a diversity of alkaloid and peptide cyanotoxins which have been suggested to both pose threats to human and environmental health worldwide (Hawkins et al., 1985;Carmichael and Falconer, 1993;Kuiper-Goodman et al., 1999;Sivonen and Jones, 1999;Hitzfeld et al., 2000;Ettoumi et al., 2011). ...
L’enrichissement des milieux aquatiques en éléments nutritifs provoque la prolifération de cyanobactéries. Parmi elles, certaines souches sont capables de synthétiser des métabolites secondaires, toxiques pour les animaux et l’homme. Les microcystines, hépatotoxines, produites par des cyanobactéries du genre Microcystis représentent les toxines les plus fréquemment trouvées dans les eaux contaminées, amenant l’Organisation Mondiale de la Santé à établir une limite dans les eaux potables à 1 µg L-1. De fortes concentrations peuvent être trouvées dans les eaux d’irrigation, pour lesquelles aucun contrôle n’est en vigueur et induire des risques de contamination des sols et des produits agricoles. Les toxines sont capables de s’accumuler dans un sol agricole, lors d’apports successifs, par irrigation, de faibles doses de microcystines (<100µg équiv. MC-LR L-1). Mais elles restent peu adsorbées au sol et sont facilement lessivables et biodisponibles. L’activité biologique des sols reste quant à elle, peu modifiée et seule l’activité des bactéries nitrifiantes est stimulée. Concernant les plants de tomates Solanum lycopersicum variété MicroTom, le processus de germination des graines est accéléré, durant les 14 jours post-semis. Cependant par la suite, la croissance et les paramètres physiologiques ne sont pas modifiés par ces apports quotidiens de microcystines. Cependant, la plante absorbe les microcystines présentes dans le sol et les redistribue dans ses parties aériennes où elles sont trouvées liées à d’autres molécules. Malgré cela, aucune microcystine libre ou liée, n’a été détectée dans les parties comestibles de la plante, d’où un risque sanitaire nul pour les consommateurs de ces fruits.
... Keeping in mind its evolutionary significance, phytochemical and pharmacological studies of this group may lead to the discovery of certain novel metabolites having unique therapeutic potential. Cyanobacteria, are arguably a group of the photosynthetic oxygen-evolving prokaryotes that originated 2.8 billion years ago (Schopf and Packer, 1987;Schwartzman et al., 2008), could have faced many environmental stresses during evolution, have been perceived as the novel source of antibiotic, antifungal, anticancer, antihelminthic, enzyme inhibitors, photosynthesis inhibitors, hemagglutinins, antiviral, anticoagulant, antiinflammatory, antimalarial, antiprotozoal, antituberculosis, and immunosuppressive activities that show prodigious bioactive potential for drug targeting (Burja et al., 2001;Tan, 2007Tan, , 2010Tan, , 2013Nunnery et al., 2010;Mayer et al., 2011;Gerwick and Moore, 2012;Namikoshi and Rinehart, 1996;Jaiswal et al., 2008, Sivonen andB€ orner, 2008;Prasanna et al., 2010;Vestola et al., 2014;Singh et al., 2005;Volk and Furkert, 2006;Bhatnagar and Kim, 2010;Pearson et al., 2010;Jones et al., 2011). Curacin A, a mixed polyketide, nonribosomal peptide possessing antimitotic and antiproliferative activity, was isolated from L. majuscula (Geders et al., 2007). ...
The land plants are an ancient lineage that has been constantly used in folk medicines by almost every human civilization. Several phyto-constituents with therapeutic potential have been studied for antibacterial, antifungal, antiviral, antioxidative, antiinflamatory, and anticancerous efficacy. Natural products and phytochemicals obtained from microbes and plants growing in marine and terrestrial environment have served as a major source in anticancer drug development. The search for novel drug continues in the goals of cancer therapy due to the resistance developed against chemotherapeutic drugs and their side effects. Exploring the diverse plant kingdom for their therapeutic value has been for ages and the emerging new technologies have paved new hopes in this area. This chapter aims an overview on the phytochemicals derived from the diverse plant kingdom that have therapeutic properties and are potent anticancer agents.
The Spodoptera frugiperda is a notorious pest with a broad host range. It severely damages crops, mainly in areas of the globewhere maize and sorghum are grown. The pest is difficult to control due to its adaptive nature and resistance to several insecticides available in the market. So, an identification of the alternative strategy is the prime important in the present context. Insecticidal activities of cyanobacterial extracts were evaluated in the laboratory as a biocomponent against S. frugiperda. The crude extracts of Nostoc muscorum and Spirulina sp. were prepared by using ethanol, methanol and petroleum ether solvents. Soxhlet apparatus was used for extraction. S. frugiperda larvae in their second instar were given access to fragments of maize leaf that had been treated with various cyanobacterial extracts. The findings displayed that the petroleum ether extract of N. muscorum had the lowest LC50 value of 155.22 ppm, followed by petroleum ether extracts of Spirulina, ethanol extract of N. Muscorum, methanol extract of N. muscorum, ethanol and methanol extract of Spirulina with an LC50 values of 456.02, 710, 780, 1050 and 1070 ppm respectively. Later, the effect of LC50 values on many biological parameters like the larval duration and pupal stages, the percentage of pupation, the weight of the pupal stage, the malformation of the pupal and adult stages, adult emergence percentage, fertility and the longevity of the male and female adult stages of S. frugiperda was examined. The gas chromatography-mass spectrometry (GC-MS) was used to analyse the crude extract to identify the bioactive components that were responsible for the insecticidal properties. The major compounds detected were diethyl phthalate (19.87 %), tetradecane (5.03%), hexadecanoic acid, ethyl ester (4.10 %), dodecane (4.03%), octadecane (3.72%), octadecanoic acid, methyl ester (3.40 %), ethyl oleate (3.11 %), methyl ester. octadecenoic acid (3.04 %), heptadecane (3.04 %) and phytol (3.02 %). The presence of several bioactive chemicals in the cyanobacterial extracts may be the reason for their insecticidal actions, thus it can be used as an alternative and new source to combat fall armyworm and other crop pests.
Polysaccharides are essential macromolecules for living organisms, they are widely found in plants, animals, microorganisms, and algae. However, marine polysaccharides of microalgal origin have gained prominence over the last few years for their variety of applications in food, cosmetics, and especially health. The versatility of its applications is due to the derived complex chemical structures which come from its types of monosaccharide constituent, conformation, and the presence of substituent groups, especially the sulfate group. These facts contribute to the microalgae are promising for polysaccharides production. Some challenges related to extraction, identification, and purification have yet to be overcome, however, microalgae prove to be a potential source for the production of this class of compounds. In this sense, this review presents a comprehensive description of the production of microalgae polysaccharides, aspects related to chemical structure, rheological and functional characteristics, applications, and strategies for determination, in addition to a brief description of the main challenges for the use of these macromolecules. In summary, the results presented and discussed here can further elucidate the full potential of microalgae polysaccharides for different application purposes, in addition to providing guidance for the main hot spots to be considered in future research in this scientific field.
To develop a semi-continuous cultivation strategy to improve the growth of Synechocystis sp. PCC 6803, the growth model of volume average light intensity (VALI) was established based on the light attenuation curve and the cell growth rate under different light intensities. According to the growth model, the semi-continuous cultivation strategy was optimized by controlling microalgal cells under the optimal VALI closed to 115 μmol m⁻² s⁻¹ in the culture process. The accuracy of growth model prediction and the cultivation effect of semi-continuous strategy were both verified under indoor conditions. The microalgae grew well when the VALI was in the range of 109–121 μmol m⁻² s⁻¹ (the 3rd day as a semi-continuous start replacement point, one-day replacement). The maximum total biomass was 3.36 ± 0.09 g and increased by 86.67 % compared with that without the semi-continuous cultivation strategy (1.80 ± 0.07 g). Subsequently, the microalgae were cultured in different ranges of VALI to further verify the cultivation effect of the semi-continuous strategy. The results once again confirmed that the cell growth was more favorable when the VALI was controlled in the range of 109–121 μmol m⁻² s⁻¹. Finally, the semi-continuous cultivation strategy was conducted by controlling VALI under outdoor conditions. The results showed that the maximum total biomass was 289.19 % higher than that without the semi-continuous cultivation strategy. This study indicated that the semi-continuous culture strategy of controlling the VALI in an appropriate range could accelerate the growth of Synechocystis sp. PCC 6803 in outdoor culture, and provided an important experimental basis for the large-scale culture of Synechocystis sp. PCC 6803 outdoors.
Cyanobacteria and their interactions with phytopathogenic fungi in soil-less potting mixes is a less explored aspect in the protected cultivation of crops, as fungal diseases often bring about serious losses. The nursery of tomato was raised with A. laxa amended /unamended soil-less substrate mixes [P:C, perlite: cocopeat (1:1); C:V, cocopeat: vermiculite (1:1); P:C:V, perlite: cocopeat: vermiculite: (1:1:1)]. Preliminary investigation of percent germination of tomato seeds in the different media with the treatments illustrated the differential influence of the media, and Anabaena laxa amended treatments showing highest values, including those challenged with F. solani. To further understand the nature of such interactions in the rhizosphere, transplantation of 30 d-old seedlings was undertaken in mesocosm experiments deploying soil-less substrate mixes (P:C, C:V, P:C:V) challenged with /without Fusarium solani or Rhizoctonia solani. Significant increases of 10–46% were recorded in the total soil polysaccharides and dehydrogenase activity with F. solani, and in IAA with R. solani, compared to control. Among the treatments, T4 (A. laxa ± Fs) showed an almost 60% increase in terms of nitrogen and organic carbon content. This illustrated that A. laxa effectively interacted with both fungi and improved the nutrient availability in the media; interestingly, F. solani exhibited a growth stimulatory role. Cyanobacterium-fungal interactions led to better growth of tomato plants, illustrating that A. laxa amendment can be a promising option, particularly, in P:C:V, as media for developing robust and disease-free nurseries.
Cyanobacteria can produce highly potent cyanotoxins, however, limited information is provided about their toxicity mechanisms in exposed aquatic invertebrates at the molecular level. In the present study, the effects of cyanobacterial strains from the genus Nostoc (Nostoc Z1 and Nostoc 2S3B) in Daphnia magna after waterborne exposure were investigated. Examined endpoints included immobilization (survival) in acute toxicity tests and selected gene expression changes (cyp314, cyp360A8, gst, p-gp, vtg) analyzed by the quantitative real-time polymerase chain reaction (RT-PCR). In addition, enzyme-linked immunosorbent assay (ELISA) was performed to determine whether the observed changes could be due to the presence of microcystins, the most widespread group of cyanotoxins. The results of acute toxicity tests have shown only minor changes in survival rates, which have not exceeded 20% after 48 h of exposure to either strain. On the other hand, significant changes were recorded in molecular responses of Daphnia to tested strains. Treatment with the aquatic strain Nostoc Z1 altered the expression levels of all analyzed genes. Both strains caused a significant p-glycoprotein (p-gp) induction at 75 µg ml⁻¹ which suggests the involvement of p-gp mediated multixenobiotic resistance mechanism (MXR) in facilitating excretion of toxic cyanobacterial compounds in daphnids. Additionally, these strains caused an increase in the expression levels of cyp360A8, indicating that genes related to detoxification processes could be sensitive indicators of cyanobacterial toxicity. Statistically significant induction of cyp314, as well as increases in expression of gst and vtg, were observed only after exposure to Nostoc Z1. This study indicates the potential of certain cyanobacterial metabolites to modify the expression of toxicant responsive genes involved in phase I and phase III of the xenobiotic metabolism, as well as possible interference with growth and reproduction in D. magna. Low microcystin concentrations found in both samples suggest that these cyanotoxins were not responsible for the detected toxic effects.
Anabaenopeptins and microcystins are oligopeptides produced by bloom-forming cyanobacteria. We determined in vivo effects of anabaenopeptin-B (AN-B) and two variants of microcystins of different hydrophobicity (MC-LR and MC-LF) on the physiology of Daphnia magna. Heart rate, thoracic limb activity and post-abdominal claw activity were determined by digital video analysis and oxygen consumption by Oxygraph + system. EC50 calculation and isobole methodology for interactive effects of AN-B and MC-LR mixture were used.
Daphnids' responses to all three oligopeptides were concentration- and time-dependent. MC-LF was the most potent inhibitor of heart rate, thoracic limb activity, post-abdominal claw activity and oxygen consumption. AN-B was more toxic than MC-LR toward oxygen consumption; it inhibited the movements of limbs and post-abdominal claw similarly to MC-LR, but did not inhibit heart rate. The strongest toxic effects were induced by the binary mixture of AN-B with MC-LR at the sum concentration equal to the concentration of the single compounds. First time direct synergistic toxic effects of the cyanopeptides on all the physiological parameters were found. The obtained results explain stronger disturbances in aquatic organisms caused by cyanobacterial cell contents than the individual cyanopeptides present even at higher concentrations. Other metabolites and their interactions need further studies.
The current world has many challenging situations that have to be dealt with very carefully. Among these states of affairs, the most prevailing is to discover novel sources of drugs, particularly, natural resources, which are supposed not to have adverse effects on human beings and society. During the last few decades, therefore, micro-algae are chosen among the researchers throughout the world. These photosynthetic microorganisms can yield proteins, carbohydrates, and lipids as a result of photosynthesis, thus referred to as important biological resources having a wide range of biotechnological applications in the modern world due to their ability to grow rapidly even in harsh environmental conditions. A search of these organisms for medicinal purposes has revealed important chemical prototypes for the finding of new agents, stimulating the use of refined physical techniques and new syntheses of molecules with the pharmaceutical application for human welfare. Several strains such as Anabaena, Lyngbya, Calothrix, Spirulina, Nostoc, Hapalosiphon, Phormidium, and Oscillatoria have been identified so far which can produce a wide variety of secondary metabolites having therapeutic potentials. These organisms are even being altered genetically using biotechnological interventions for the production of various active compounds having antibacterial activity such as bacteriocin, ambigol A, parsiguine, hapalindole, and hormothamnin A; antifungal activity such as fischerellin A, phytoalexin, tolytoxin, laxaphycins, ambiguines, and calophycin; and cytotoxic activity such as scytophycins, tantazoles, tolytoxin, acutiphycins, toyocamycin, and tubercidin.
The Virgilio Uribe Rowing Canal in Xochimilco, Mexico City has cyanobacterial blooms throughout the year, often of the genus Microcystis. Here we evaluated the demographic responses of Moina macrocopa in the presence of cyanotoxins obtained by freezing and sonication of blooms collected in June (2017), September (2017) and March (2018). Acute toxicity tests (LC50) showed that the median lethal concentration, on Moina macrocopa was 1.56, 1.30 and 2.56 μg/L, in June, September and March, respectively. The life table of M. macrocopa was done using 5% and 10% of the LC50, fed on Scenedesmus acutus (0.5 × 10⁶ cells/mL) with four replicates per treatment. We found that cyanotoxins reduced the survival and fecundity of Moina macrocopa. The population growth rates ranged from 0.27 and 0.49 d⁻¹ for the blooms collected in June, 0.38 and 0.52 d⁻¹ for those of September and 0.42 and 0.52 d⁻¹ for the blooms in March. We found that most of the cyanobacterial strains of the rowing canal are toxic and may have adverse effects on humans exposed to them daily.
Cyanobacteria have long been employed for green synthesis of metallic nanoparticles as they are a promising and potential source of biofuels, pharmaceuticals, colored pigments, and other important biomolecules. Current trends show an enhanced application of nanomaterials in the nanobiotechnological sector for the development of new generation medicines. Cyanobacteria are ancient photosynthetic oxygen-evolving prokaryotes that find applications for human usage as dietary supplements, medicine, and cosmetics. They produce a plethora of biologically active and chemically diverse compounds such as alkaloids, lipopeptides, cyclic peptides, fatty acid amides, polysaccharides, and UV-screening compounds. These photoautotrophs serve as potential sources for the extraction of bioactive substances, which are effective anticancerous, antimicrobial, and sunscreen agents along with several other pharmacologically important properties. Researchers have shown promising results regarding the properties of nanoconjugates of cyanobacterial bioactive photoprotective compounds in the biomedical field. So far, not even 10% of microalgal bioactive components have reached commercialized platforms due to difficulties related to solubility. Considering these factors, cyanobacteria should be considered as a potential source of natural products for drug discovery and drug delivery approaches. Nanoformulations employing a wide variety of nanoparticles and their polymerized forms could be an emerging approach to the development of new cancer drugs. This chapter highlights recent research on cyanobacterial photoprotective bioactive secondary metabolites (mycosporine-like amino acids and scytonemin) and discusses applications of their nanoconjugates as efficient drugs.
Man-made shallow fishponds in the Czech Republic have been facing high eutrophication since the 1950s. Anthropogenic eutrophication and feeding of fish have strongly affected the physicochemical properties of water and its aquatic community composition, leading to harmful algal bloom formation. In our current study, we characterized the phytoplankton community across three eutrophic ponds to assess the phytoplankton dynamics during the vegetation season. We microscopically identified and quantified 29 cyanobacterial taxa comprising non-toxigenic and toxigenic species. Further, a detailed cyanopeptides (CNPs) profiling was performed using molecular networking analysis of liquid chromatography-tandem mass spectrometry (LC-MS/MS) data coupled with a dereplication strategy. This MS networking approach, coupled with dereplication, on the online global natural product social networking (GNPS) web platform led us to putatively identify forty CNPs: fourteen anabaenopeptins, ten microcystins, five cyanopeptolins, six microginins, two cyanobactins, a dipeptide radiosumin, a cyclooctapeptide planktocyclin, and epidolastatin 12. We applied the binary logistic regression to estimate the CNPs producers by correlating the GNPS data with the species abundance. The usage of the GNPS web platform proved a valuable approach for the rapid and simultaneous detection of a large number of peptides and rapid risk assessments for harmful blooms.
Man-made shallow fishponds in the Czech Republic have been facing a high eutrophication since 1950s. Anthropogenic eutrophication and feeding of fish have strongly affected the physico-chemical properties of water and its aquatic community composition leading to harmful algal bloom formation. In our current study, we have characterised the phytoplankton community across three hypertrophic ponds to assess the phytoplankton dynamics during the vegetation season. We microscopically identified and quantified 29 cyanobacterial taxa comprised of non-toxigenic and toxigenic species. Further, a detailed cyanopeptides (CNPs) profiling was performed using molecular networking analysis of liquid chromatography tandem mass spectrometry (LC–MS/MS) data coupled with dereplication strategy. This MS networking approach coupled with dereplication on online global natural product social networking (GNPS) web platform led us to putatively identify forty CNPs: fourteen anabaenopeptins, ten microcystins, five cyanopeptolins, six microginins, two cyanobactins, a dipeptide radiosumin, a cyclooctapeptide planktocyclin and epidolastatin12. We have applied the binary logistic regression to estimate the CNPs producer by correlating the GNPS data with the species abundance. Usage of The combination of molecular networking and dereplication on online global natural product social networking (GNPS) web platform has proved as a valuable approach for rapid and simultaneous detection of high number of peptides, and rapidly assessing the risk for harmful bloom.
The world of nature provides a never-ending set of fascinating problems for the chemist. Many of the most intriguing problems, however, concern compounds available in only truly minute quantities. One solution is to focus on bioassay-guided separations. In so doing one can isolate compounds with novel structures or unsuspected activities from almost any phylum, including tunicates, sponges, insects, or even the much-studied terrestrial plants, as exemplified in several recent studies in our laboratory involving activities ranging from antiviral and antimicrobial activity to cytotoxicity and immunomodulation. Moreover, newer spectroscopic techniques, especially fast atom bombardment mass spectrometry and tandem mass spectrometry, enhance one's ability to study compounds present in minute quantities, including those of importance to the host organism, such as neuropeptides in insects or marine invertebrates.
Puwainaphycin C, a cardioactive agent which elicits a strong, positive inotropic effect in isolated mouse atria, is a novel chlorine-containing cyclic decapeptide from a Hawaiian terrestrial Anabaena sp. (strain BQ-16-1). Detailed spectral analysis of the intact molecule and an acid hydrolysis study show that puwainaphycin C possesses an unusual β-amino acid unit, viz., a 3-amino-14-chloro-2-hydroxy-4-methylpalmityl residue, and nine known amino acid units. Using difference NOE spectroscopy and two-dimensional 13C-13C and carbon-detected 13C-15N correlation spectroscopy to sequence the 10 amino acid residues, the gross structure of puwainaphycin C has been shown to be cyclic(3-amino-14-chloro-2-hydroxy-4-methylpalmityl-valyl-2-aminobut-2(E)-enoyl- threonyl-threonyl-glutaminyl-glycyl-O-methylthreonyl-N-methylasparaginyl-prolyl) . Puwainaphycin D, a closely related inactive compound, differs from puwainaphycin C in having a second valyl unit at the site occupied by Thr-2.
The first synthesis of 3-amino-2-methylpentanoic acids is reported. Comparison of the synthetic 2,3 and 2,3 acids with 3-amino-2-methylpentanoic acid obtained by degradation of the antifungal depsipeptide majusculamide C indicates that majusculamide C, 57-normajusculamide C, and the antitumor agents dolastatins 11 and 12 have the 2,3 configurations at the chiral centers in their β-amino acid component.
The structure of halichondramide (2), an antifungal macrolide from the Pacific sponge Halichondria sp., was elucidated by interpretation of spectral data.
Aeruginosin 298-A was isolated from the freshwater blue-green alga Microcystis aeruginosa (NIES-298). Its structure was elucidated to be 1 on the basis of 2D NMR data. This linear peptide inhibited thrombin and trypsin potently.
Swinholide-A (a) a novel 22-membered macrolide has been isolated from a Red Sea sponge. The structure of the tetraformate () has been determined on basis of spectral data using 2D-NMR correlations.
Linear peptide 2, Adda-D-Glu(γ)-Mdhb-D-MeAsp(β)-L-Arg-OH, was isolated from cultured Nodularia spumigena and was analyzed in the cells after one week's (1:2 : 30:1) to eight week's (>100:1) cultivation. Three linear peptides, Adda-D-Glu(γ)-Mdha-D-Ala-L-Leu-D-MeAsp(β)-L-Arg-OH (3), L-Leu-D-MeAsp(β)-L-Arg-Adda-D-Glu(γ)-Mdha-D-Ala-OH (4), and L-Phe-D-MeAsp(β)-L-Arg-Adda-D-Glu(γ)-Mdha-D-Ala-OH (5) were obtained from a water bloom of Microcystis spp. collected from Homer Lake (Illinois). Some of these linear peptides (2,3) are thought to be biogenetic precursors of nodularin and microcystins. Linear peptides 2, 3, and 4 did not show apparent toxicity at 1.0, 1.1, and 2.25 mg/kg, respectively, in a mouse bioassay (ip). Feeding experiments using 13C-labeled precursors established that the 2-, 6- and 8-methyl and 9-methoxy carbons of the unusual (2S,3S,8S,9S)-3-amino-9-methoxy-2,6,8-trimethyl-10-phenyl-4,6-decadienoic acid (Adda) unit of 1 were clearly derived from L-methionine.
Four novel depsipeptides, aeruginopeptins (1–4) were isolated from toxic cyanobacteria, Microcystis aeruginosa TAC 95 and M228 which also produce microcystins LR and YR, respectively. Their structures were mainly determined by 2D-NMR techniques and MS/MS method.
The isolation of a new cyclic hexapeptide is reported from a marine ascidian Lissoclinum bistratum. The structure was determined by NMR, mass spectrometry and X-ray crystallographic techniques. Cytotoxicity against MRC5CV1 and T24 cells expressed as IC50 was 0.5 μg/mL.
Arenastatin A (1) has been isolated from the Okinawan marine sponge Dysidea arenaria and the chemical structure including parts of the absolute configurations elucidated. Arenastatin A (1) is a cyclic didepsipeptide and exhibited extremely potent cytotoxicity against KB cells at IC50 5 pg/ml.
Microginin, an angiotensin-converting enzyme inhibitory pentapeptide, was isolated from the freshwater blue-green alga Microcystis aeruginosa. Its structure was elucidated to be 1 on the basis of 2D NMR data and chemical degradation.
A novel peptide, konbamide 1, with calmodulin antagonistic activity has been isolated from the Okinawan marine sponge Theonella sp. and the structure elucidated to be a unique hexapeptide with an ureido bond on the basis of spectroscopic data, including two-dimensional NMR techniques and FAB MS–MS analysis (FAB = fast atom bombardment).
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Puwainaphycins A–E, one of which (C) is a potent cardioactive agent in isolated mouse atria, are cyclic decapeptides that have beeen isolated from a terrestrial blue-green alga Annabaena sp. BQ-16-1. The structures of puwainaphycins A–E, including most of the stereochemical features, have been elucidated by a combination of spectral and chemical methods.
A new cyclic depsipeptide, cyanopeptolin SS, was isolated from a water bloom in Leipzig (Germany) dominated by Microcystis aeruginosa (Kützing) Kützing. The structure was determined by amino acid analysis, mass spectrometry, two-dimensional nuclear magnetic resonance spectroscopy, and Fourier-transformed infrared micro-spectroscopy. The structure of cyanopeptolin SS was similar to the previously reported monosulphated cyanopeptolin S isolated from the same water bloom, but cyanopeptolin SS contained a disulphated glyceric acid side chain. In contrast to microcystins, which co-occurred in the same water bloom, cyanopeptolin S and cyanopeptolin SS had no toxic effects on isolated rat hepatocytes. Cyanopeptolin S and SS inhibited trypsin, thrombin and plasmin. Their effects on protein phosphatases are discussed.
Two antineoplastic cyclic depsipeptides designated dolastatin 11(1) and dolastatin 12 (2) were isolated from the Indian Ocean sea hare Dolabella auricularia. Dolastatins 11 and 12 inhibited growth of the PS leukemia with ED50 2.7 × 10-3 and 7.5 × 10-2 μg/mL respectively. Detailed structural studies employing 400 MHz 1H,1H-COSY, 1H,13C-COSY, NOE, and HMBC experiments (in addition to acid and base hydrolysis, followed by GC-MS analysis) led to structure 1 for dolastatin 11 and to structure 2 for dolastatin 12.
From the marine gastropod mollusc Stylocheilus longicauda we isolated aplysiatoxin and debromoaplysiatoxin (LD100, 0.3 mg/kg) and equal amounts of their non-toxic acetates. The structures of these compounds were deduced by spectral studies and by reductive and hydrolytic degradation.
A novel peptide, keramamide A 1, has been isolated from the Okinawan marine sponge Theonella sp. and the structure established as a unique hexapeptide containing a hitherto unknown amino acid 6-chloro-5-hydroxy-N-methyltryptophan, and possessing an unusual ureido bond. The structural assignment was made on the basis of spectroscopic results (two-dimensional NMR: 1H–1H COSY, NOESY, ROESY, COLOC, HMQC, HMBC and HOHAHA; and FAB MS/MS).
Two cyclic peptides, anabaenopeptins A (1) and B (2), were isolated as a third group of bioactive compounds fromAnabaena flos-aquae NRC 525-17. Their structures were determined by 2D-NMR techniques and Marfey's method combined with LC/MS.
Oscillamide Y, a chymotrypsin inhibitor, was isolated from freshwater toxic cyanobacterium Oscillatoria agardhii. The structure was elucidated to be 1 by chemical degradation and 2D NMR analyses.
Micropeptin 90, a plasmin and trypsin inhibitor, was isolated from the cultured freshwater blue-green alga Microcystis aeruginosa (NIES-90). Its structure was elucidated to be 1 on the basis of 2D NMR data and chemical degradation. This cyclic depsipeptide inhibited plasmin and trypsin potently with IC50 of 0.1 and 2.0 μg/ml, respectively.
Puwainaphycins A–E, one of which (C) is a potent cardioactive agent in isolated mouse atria, are cyclic decapeptides that have beeen isolated from a terrestrial blue-green alga Annabaena sp. BQ-16-1. The structures of puwainaphycins A–E, including most of the stereochemical features, have been elucidated by a combination of spectral and chemical methods.
Motuporin (1), a cyclic pentapeptide that is a potent protein phosphatase-1 inhibitor and cytotoxin, has been isolated from the marine sponge Theonella swinhoei collected in Papua New Guinea. The structure of motuporin was elucidated by spectroscopic analysis and chemical degradation.
A synthesis of the keto-triol formyl enamine moiety (3) in the marine metabolite halichondramide (1) is described. The synthesis features judicious applications of the Evans chiral aldol protocol in combination with the controlled ring opening of chiral α-epoxy alcohol precursor molecules to elaborate the units (5) and (6). A Wadsworth-Emmons coupling between (5) and (6) next provided (18), which was then elaborated to (3) via the key intermediates (19) and (21).
Oscillapeptin, a new cyclic depsipeptide that inhibits elastase and chymotrypsin, was isolated from the cyanobacterium Oscillatoria agardhii (NIES-204) and its structure was elucidated by extensive 2D NMR and chemical degradation. Oscillapeptin inhibited elastase and chymotrypsin with an IC50 of 0.3 and 2.2 μg/ml, respectively.
Micropeptins A and B were isolated from the cultured freshwater blue-green alga Microcystis aeruginosa. Their structures were elucidated to be 1 and 2 on the basis of 2D NMR data and chemical degradation. These cyclic depsipeptides inhibited plasmin and trypsin potently.
Aeruginosins 98-A and B, trypsin inhibitors, were isolated from the cultured freshwater blue-green alga Microcystis aeruginosa. Their structures were elucidated to be 1 and 2 respectively on the basis of 2D NMR data and chemical degradation. These peptides inhibited trypsin potently with an IC50 of 0.6 μg/ml.
Majusculamide C [1], a cyclic depsipeptide metabolite of the blue-green alga Lyngbya majuscula, has been isolated from the sponge Ptilocaulis trachys collected at Enewetak Atoll in the Marshall Islands. The absolute configuration of the novel β amino acid 2-methyl-3-aminopentanoic acid (MAP), a component of the structure of 1, has been determined to be 2S,3R.
The lipophilic extract of the cultured terrestrial blue-green alga Scytonema pseudohofmanni Bharadwaja contains five novel macrolides, scytophycins A (1), B (2), C (3), D (4), and E (5), which exhibit cytotoxicity and antifungal activity. The structures of 1-5 have been determined mainly from spectroscopic data. The relative stereochemistries of the scytophycins are based on an X-ray crystallographic analysis of a transformation product of scytophycin C (8) and comparison of the 1H and 13C NMR spectra of 1-5. The absolute stereochemistries of the scytophycins have been deduced from a circular dichroism study of the dibenzoate ester 16, obtained in five steps from scytophycin B, and comparison of the CD curves of 1-5. These novel secondary metabolites appear to be biogenetically related to the marine natural products swinholide A, ulapualides A and B, and kabiramide C.
Three new hepatotoxic cyclic heptapeptides in the microcystin class were isolated from the cyanobacterium (blue-green alga) Nostoc sp. strain 152 and assigned structures based on their high-resolution FABMS, FABMS/MS, 1H and 13C NMR spectra, amino acid analysis, and GC on a chiral capillary column. All three toxins (1-3) have 9-acetoxy-3-amino-2,6,8-trimethyl-10-phenyl-4,6-decadienoic acid as an unusual structural component (Scheme I) instead of the corresponding 9-methoxyl derivative (Adda) found in the microcystins.
Malyngamide C (1), a chlorine-containing amide of 7(S)-methoxytetradec-4(E)-enoic acid, was found to be a major constituent of the lipophilic extract of Lyngbya majuscula from Fanning Island. The complete structure, including absolute stereochemistry, was determined by spectral and chemical studies of malyngamide C and several derivatives. Three structurally related compounds, viz., malyngamide C acetate (3), deoxymalyngamide C (4), and dideoxymalyngamide C (5), were shown to be minor constituents of the alga.
Optical and proton NMR spectral studies of the aplysiatoxins and derivatives, degradation products of the toxins, and an X-ray crystallographic analysis of 19,21-dibromoaplysiatoxin show that the absolute configurations of the ten asymmetric carbons are 3S,4R,7S,9S,10S,11R,12S,15S,29R,30R. The 31-nor compound, oscillatoxin A, has the same absolute stereochemistry at C(3), C(4), C(7), C(9), C(10), C(11), C(12), C(15), and C(29).
Majusculamide C, a novel cyclic depsipeptide that inhibits the growth of a number of fungal plant pathogens, has been shown to consist of seven α-amino acid units, one β-amino acid unit, and one hydroxy acid unit. The structures of the units have been determined by acid hydrolysis of the fungicide to glycine, L-alanine, L-N-methylvaline, L-N,O-dimethyltyrosine, L-N-methylisoleucine, racemic 2-amino-4-methylpentanone, 3-amino-2-methylpentanoic acid of undefined stereochemistry, and N-[2(S)-hydroxy-3(S)-methylpentanoyl]glycine. Sequencing of the units implied from the structures of the hydrolysis products has been achieved by mass spcetral and proton NOE studies.
Larger scale isolation of microcystins, cyclic heptapeptide hepatotoxins, from a water bloom of Microcystis spp. collected from Homer Lake (Illinois) gave the previously reported 1-5, additional quantities of [L-MeSer(7)]microcystin-LR (6), and microcystin-(H-4)YR [8, (H-4)Y = 1',2',3',4'-tetrahydrotyrosine], which were previously isolated in insufficient amounts to complete the structure assignment, and seven more microcystins, 9-15. A general method for assigning the structures of cyclic peptides containing alpha,beta-unsaturated amino acid unit(s) developed with nodularin, a cyclic pentapeptide hepatotoxin, was applied to confirm the previously assigned structures of 1-5 and to assign the structures of [D-Asp(3)]microcystin-LR (9) and the. new microcystin-HilR (10, Hil = homoisoleucine). The method consists of linearization of a cyclic molecule by a one-pot reaction sequence (ozonolysis followed by NaBH4 reduction) and tandem FARMS (FABMS/CID/MS) analysis of the product (linear peptide). A new microcystin, 11, was assigned the structure [L-MeLan(7)]microcystin-LR (MeLan = N-methyllanthionine) and synthesized from 1 and L-Cys. Four linear peptides 12-15, which are reasonable biogenetic precursors of the cyclic compounds, were also assigned structures based on their FABMS/CID/MS data.
A general method has been developed for assigning the structures of nodularin, a potent hepatotoxin, tumor promoter, and protein phosphatase inhibitor, and minor components isolated from a cultured and a bloom sample of the cyanobacterium Nodularia spumigena. It consists of (1) FABMS analysis (determination of molecular weight and molecular formula), (2) H-1 NMR spectroscopy on the parent compound and chiral GC analysis of an acid hydrolyzate (identification and stereochemistry of amino acid components), (3) ozonolysis followed by NaBH4 reduction (conversion to a linear peptide), and (4) FABMS/CID/MS analyses of the linear peptide and the parent compound (sequence analysis). The method has been employed in assigning structures to three new nodularins (2-4) and can be applied to other cyclic peptides containing alpha,beta-dehydroamino acid unit(s), especially the related microcystins, cyclic heptapeptide hepatotoxins. Two nodularins, [DMAdda(3)]nodularin (2) and [(6Z)-Adda(3)] nodularin (3), were obtained from a bloom sample collected from Lake Ellesmere (New Zealand), and [D-Asp(1)] nodularin (4) was isolated from cultured cells (strain L-575). The LD50s of 2 and 4 were 150 and 75 mu g/kg (ip, mice), respectively, but 3 did not show apparent toxicity at 2.0 mg/kg.
Eleven minor components were isolated, together with microcystin-LR, (LR, I, Scheme I) as the principal toxin (ca. 90% of the toxic components), from Microcystis cyanobacteria (blue-green algae) collected from Homer Lake (Illinois) in the summer of 1988. The components were characterized by amino acid analysis and HRFABMS, FABMS/MS, H-1 NMR, and UV spectroscopic methods as microcystins-RR (2) and -YR (3) (Scheme I) and nine new microcystins. The structures of seven new microcystins were assigned as [DMAdda5]microcystin-LR (4), [Dha7]microcystin-LR (5), microcystin-FR (6), microcystin-AR (7), microcystin-M(O)R (8), [Mser7]microcystin-LR (9), and microcystin-WR (12). Compound 4 is the first microcystin containing 9-O-demethyl-Adda, while phenylalanine, N-methylserine, and tryptophan are also new variations in amino acid components of microcystins. Compound 11 was deduced to be a (C3H7O) monoester of the alpha-carboxyl on the Glu unit of LR (1). New microcystin 11 caused no apparent toxic effects in mice dosed ip at 1 mg/kg, while the others had LD50's of 90-800-mu-g/kg.
From the sea hare Stylocheilus longicauda we have isolated, in addition to the previously reported aplysiatoxins (1, 2), a novel nontoxic amide of composition C28H44ClNO6. Stylocheilamide (3) is a tertiary amide constructed of a methoxyolefinic C14 acid and a methyl(2-chloro-3-cyclohexyl-2-propenyl)amine. The highly functionalized carbocyclic ring gives rise to a related compound 4, differing only by the elements of HOAc. The structures have been elucidated by spectral analysis and chemical degradation. A key degradation product (8) was crystalline and its structure was determined by X-ray diffraction.