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In the last decades, an increasing attention has been directed toward the possibilities of growing algae commercially. This interest has been partially due to the fact that some strains of microalgae and cyanobacteria have demonstrated the ability to produce a variety of bioactive products. Both, primary and secondary metabolism of these microorganisms has been demonstrated to play a key role in the production of special chemicals. Antioxidants, for instance, can be produced by some algal strains to protect photosynthetic cells from oxidative stress. Microalgae can produce a variety of polyunsaturated and monounsaturated fatty acids with clear health benefits for human nutrition. Potential products obtained from cyanobacteria and microalgae exhibiting interesting medical properties include polysaccharides, glycerol, glycoproteins, and antibiotics. From the aforementioned products, especially relevant has become the search of new antibiotics. The potential spread of bacterial resistance and the foreseen decrease on efficiency on antibiotics, has largely stimulated the research on novel antibiotics sources. Among these sources, cyanobacteria and microalgae have demonstrated a vast and just barely explored potential.
Norwegian Institute for Water Research, Oslo, Norway
Carlos Escudero-Oñate*
Norwegian Institute for Water Research, Oslo, Norway
*Address all correspondence to: carlos.escudero@niva.no
1. Introduction
Cyanobacteria (prokaryotic green-blue algae) and microalgae (eukaryotic microalgae) are regularly found in water bodies, desert crusts, or even in symbiosis with other animals. They can live in large varieties of environmental conditions, including low or high temperatures, high-light intensities, pH and salinity [1]. In the last decades, increasing attention has been paid to the potential of growing these kinds of organisms with commercial purposes. Part of the added value of this type of biomass is based on the fact that it can be used in human and animal nutrition (i.e. fish feed in aquaculture facilities). Moreover, some extracts from microalgae can be used to produce cosmetics and a variety of different bioactive products, such as pharmaceutical compounds [2, 3, 4]. The diversity of cyanobacteria and microalgae is immense, with species, genera, or even classes being discovered every year. On the estimated millions of exiting species, about 30,000 have been described; but nowadays, not more than a dozen is regularly cultivated and exploited in large scale for commercial biotechnological purposes. On top of that, research on how the culture conditions affect the production of important bioactive substances remains nowadays very scarce. Some authors, such as Spoehr and Milner [5], proved that manipulating microalgae or cyanobacteria growth conditions, for instance, by applying different forms of stress to the cells, could promote the production of biomass with valuable secondary metabolites, some of which presents pharmaceutical and/or industrial values. In most of the cases, the production of valuable metabolic products by cyanobacteria and microalgae is a two-step process. In the first step, the microorganisms are grown under optimal conditions to maximize the production of biomass. This process is followed by a second step where stress factors, such as high light intensity or nutrients deprivation, are applied to the culture to induce the production of valuable secondary metabolites with the pursued pharmaceutical [6, 7] or antioxidant properties. In this chapter, the production of a variety of bioactive compounds by cyanobacteria and microalgae has been reviewed.
2. Valuable bioactive products from cyanobacteria and microalgae
Variations in temperature, light, pH, salinity and nutrient availability have been extensively investigated to study their impact on microalgae growth and their primary and secondary metabolic products. Primary metabolites are those directly involved in normal growth development, reproduction, cell division, or metabolism. They include for instance the production of lipid, such as polyunsaturated fatty acids (PUFA) [8, 9, 10, 11], antioxidants such as carotenoids, and some types of proteins (Figure 1). Secondary metabolites are those compounds that are not used by organisms for their primary needs and include compounds that act as hormones, antibiotics, or toxins, among others [12]. The production of secondary metabolites appears to be specie and strain specific [13], and is possibly associated to the exposure of the microorganism to specific environmental conditions [6, 14] caused, for instance, by stress factors. In a study carried out by Lustigaman in 1988, the production of antibiotic activity by Dunaliella spp. was investigated. The study was based on isolating extracts of these microalgae from two different environmental scenarios; one clean and one polluted water system. The study demonstrated that nonproteinous substances inhibiting the activity of the bacteria Escherichia coli were only produced by the microalgae Dunaliella spp. under exposure to the polluted water. It was, therefore, suggested that microalgae growing in adverse conditions are more likely to produce secondary metabolites with antibacterial activity [15].
Figure 1.
Example of some primary metabolic routes and their products in microalgae. Adapted from Rosenberg et al. [16].
Nowadays, the major products obtained from microalgae with industrial use are carotenoids and algal biomass, which are mainly used for human and animal feed and for aquaculture. Microalgae can also produce other antioxidants, such as vitamins C and E, and even butylated hydroxytoluene (BHT). Fatty acids are also produced as primary metabolic products, playing an important role protecting the cells against oxidative stress. Other metabolic products obtained from microalgae and exhibiting medical properties are special polysaccharides, glycerol and myscosporine-like amino acids (MAA). In addition to the aforementioned compound families, glycoproteins, antifreeze proteins and antibiotics can also be produced by these microorganisms. Some of these substances have demonstrated a set of interesting bioactivities [11]. An overview of the potential bioactive metabolites is presented in Figure 2.
Figure 2.
Overview of the potential bioactive metabolites produced by microalgae and cyanobacteria. Adapted from Skjånes et al. [11].
2.1. Antioxidants
Eukaryotic microalgae and cyanobacteria are often exposed to high oxygen levels and high irradiance conditions. As a response to this potential oxidative stress, these organisms have developed defense systems based on the production of different antioxidants. The main goal of these substances is to preserve cells from oxidative stress, which may otherwise cause damage to essential biological structures, such as DNA, proteins and lipids. Oxidative stress in humans and animals can also lead to severe health problems, such as atherogenesis, cancer, neurodegenerative diseases, infant retinopathy, muscular degeneration and renal failure, along with other problems [17, 18, 19]. Dietary intake of antioxidants from these organisms has shown the ability to limit or prevent certain health issues. For instance, many substances found in algae, such as carotenoids, vitamins C and E or butylated hydroxytoluene (BHT) have such antioxidant effects [11]. Carotenoids have been largely used as supplement in human nutrition as well as in food and animal feed, poultry and fish. Vitamin C may be found in tablets for human consumption as well as in meat, where it has been largely used to prevent oxidation processes and the discoloration of the product during storage. Vitamin E can be commonly found in supplements for human health and has been largely used in food industry. Another largely used antioxidant is astaxanthine. This substance has become very popular recently as supplement for human nutrition and is commonly found in, i.e., salmon food formulations to intensify the pigmentation of the fish growth in aquaculture facilities. Table 1 gathers some examples of microalgae and the type of antioxidant substance that they produce.
Fatty acids are essential components of the diet. They can occur in the cells as glycolipids and phospholipids forming the cellular membranes, or as storage products for energy and carbon in the form of triglycerides [27]. In some cases, triglycerides may also have a role protecting against oxidative stress, and the lack of these nutrients can cause severe damage to the organism. Fatty acids can be produced by eukaryotic microalgae and cyanobacteria, and in some cases they can produce them in large amounts [28]. The truly essential fatty acids are omega-3 fatty acids, such as linoleic acid and α-linoleic acid. Both humans and animals are dependent on obtaining them from the diet, because they are used as starting points for building longer chains of fatty acids. Food supplements of omega-3 are known to have beneficial health effects in the prevention of coronary heart disease, hypertension, type 2 diabetes, renal disease and chronic obstructive pulmonary disease, among others [29]. A summary including the production of fatty acids produced by microalgae is presented in Table 2. Some of the industrial applications of fatty acids include cosmetic formulations, food, personal care, and pharmaceutical products.
Certain polysaccharides from microalgae have been shown to have remarkable biomedical properties. Several studies have demonstrated that microalgae, such as Chlorella vulgaris and Scenedesmus quadricauda are able to presumably produce sulfated polysaccharides that function as protection against microcystin oxidative stress [35]. Crude polysaccharide extracts obtained from Chlorella stigmatophora and Phaeodactylum tricornutum showed anti-inflammatory activity in the carrageenan-induced paw edema test [36]. Moreover, other crude polysaccharide extracts from Chlorella pyrenoidosa presented antitumoral activity against A549 (cell human lung carcinoma) in vitro [37]. Furthermore, polysaccharides can also present other health-promoting effects on, for instance, gastric ulcers, wounds and constipations [38, 39]. However, their exact function in the algae cells remains still unknown.
2.4. Glycerol
Glycerol can function as osmoregulator and osmoprotector of enzymes. This substance has been accumulated in substantial amounts in halotolerant species during salt stress conditions. The production of glycerol in algae is regulated by external water activity, but high light intensities may inhibit its production [40]. In some cases, the algae can also excrete glycerol as a response to high concentrations of CO2 rather than salt stress condition [41]. Glycerol is widely used in cosmetics, pharmaceuticals, paint, food, tobacco, pulp and paper, or in the production of a large variety of chemicals [42]. Some examples of microalgae producing glycerol are Brachiomonas submarina [43], Chlamydomonas spp. [41] and Dumaliella salina [44]. Glycerol can be found in a large variety of commercial products and applications, such as cosmetics and food products, drugs and pharmaceuticals.
2.5. Lectins
Lectins are carbohydrate-binding proteins that are located within protein bodies in the cell. Lectins from algae have high specificity for complex oligosaccharides, glycoproteins, or glycolipids. They are useful in medical science, for instance, for the detection of disease-related alterations of glycan synthesis, and for cell markers for diagnosis purposes including infectious agents, i.e., viruses, bacteria, fungi and/or parasites. Different strains of Chlorella, such as Chlorella minutissima [45], Chlorella pyrenoidosa [46, 47] and Chlorella spp. [45] produce metabolites with antimicrobial activity and this activity has been preliminary hypothesized to be due to lectins [47]. Studies conducted with other algae strains, such as Desmococcus olivaceus [45], Scenedesmus quadricauda [46] and Scenedesmus sp. [45, 48], have reported that the production of these lectins can be induced by growth-limiting conditions like nutrient deprivation and/or light stress conditions [49].
Some companies, for instance, Lectin Labs Ltd., have developed lectin formulations, and claim that these lectins interfere or destroy the development of the disease-causing processes, even in cases where antibiotics are ineffective.
2.6. Mycosporine-like amino acids
Mycosporine-like amino acids (MAA) are a group of molecules consisting of an amino acid bound to a chromophore molecule that absorbs light. These amino acids are involved in protecting the organism against UV radiation and are produced in significant amounts by, for example, the high UV-tolerant snow algae Chlamydomonas nivalis and other green algae species. The production of MAA is induced by exposing the microalgae to UV-light and the resulting irradiance stress reactions. Nevertheless, there are indicators pointing out that a decrease in nitrogen levels leads to a decrease in the production of MAA [50, 51]. MAAs from algae have been explored for commercial purposes which have resulted, for instance, in commercial skin-care products for UV protection [52]. Some examples of microalgae that produce MAA are Ankistrodesmus spiralis, Chlorella minutissima, Scenedesmus sp. and Scotiella nivalis [51].
2.7. Glycoproteins
Glycoproteins are relevant biological structures formed by a protein covalently linked to one or more carbohydrate units. These structures have a large set of biological functionalities and some microalgae have demonstrated to be a potential source of them. For instance, a glycoprotein obtained from Chlorella vulgaris was found to exhibit anticancer activity through anti-metastatic immunopotentiation [53, 54]. Other microalgae presenting anticancer activity are Desmococcus olivaceus [45], Scenedesmus sp. [45, 48], Dunaliella bardawil [55] and Dunaliella salina [44], among others. However, little has been done to identify similar compounds with activity from other algal species, nor to consider possibilities for optimization of the production of these glycoproteins by manipulating growth conditions [11].
2.8. Antifreeze proteins
Cold adapted strains of green algae, such as those living in polar environments, are often producers of antifreeze proteins (AFPs), also designated as ice structuring proteins (ISPs). These proteins are key elements for the survival of some organisms, since they prevent damages occurring as a result of very low temperatures. They exhibit unique properties because they are able to bind to ice crystals, prevent recrystallization and protect other proteins from damage. AFPs extracted from algae or other microorganisms can be used for cryopreservation, frozen food preservation, transgenic crops and even weather modification [56, 57, 58]. There are some microalgae such as Chlorella pyrenoidosa that can produce AFPs that additionally exhibit antifungal properties [46, 47]. AFPs are currently being explored in some formulations to reduce cold-induced damage in medical, food and cosmetic products with the target of lengthening shelf life of the frozen gods. The extraordinary properties of AFPs allow hypothesizing a growing number of businesses including AFPs in their future formulation of products.
2.9. Antibiotic activity
Some strains of microalgae can produce metabolites with antibiotic activity aimed at killing or inhibiting bacterial growth. In some cases, this activity has only been identified in general extracts from the algal culture, without properly determining the chemical identity of the active compound/s [45, 47]. There are indications that antibiotics are more likely to occur in strains isolated from environments polluted by bacteria than in strains isolated from cleaner environments [59]. For instance, the methanolic extracts of Tetraspora cylindrica present antibacterial activity against Corynebacterium diphtheria, Klebsiella pneumoniae and Shigella boydii, among others. These extracts also present antifungal activity against: Curvularia lunata, Fusarium sporotrichoids, Macrophomina phaseolina, Rhizoctonis solani, Sclerotium rolfsii and Trichoderma harzianum [60].
In the last decade, the screening and bioprospecting of microalgae and cyanobacteria for antibiotics and pharmacologically active compounds has received a lot of attention. This is because a large number of antibiotic compounds, many of them with unusual and novel structures, have been isolated and characterized from extracts of microalgae [15]. Similarly, many cyanobacteria have been shown to produce antiviral and antineoplastic compounds. A range of pharmacological activities have also been observed in some extracts of microalgae which active principles, in most of the cases, are still unknown. Several of these bioactive compounds found in microalgae extracts may find application in human or veterinary medicine and agriculture. Others could be used, for instance, as research tools or as structural models for the development of new drugs [15]. Microalgae are particularly attractive as natural sources of bioactive molecules because they have the potential to produce these compounds in culture. This enables the production of structurally complex molecules which are difficult or impossible to produce by chemical synthesis [61].
Many of the antibiotics and pharmaceuticals in current use have their origins in nature and are the product of systematic screening of terrestrial organisms, such as higher plants and soil microbes. For instance, of approximately 13500 known naturally occurring antibiotics, 5500 are produced by actinomycetes, while approximately 3300 are produced by higher plants and, of these, about 90 are in current medical use [62]. Much of the work concerned with the isolation, screening, and physiology of antibiotic-producing microorganisms has been focused on heterotrophs. However, very little attention has been paid to other groups, such as microalgae which are able to grow under diverse nutritional conditions: photo-autotrophically or chemoheterotrophically [63].
Moreover, many marine algae produce antibiotics substances that are capable of inhibiting bacteria, viruses, fungi and other epibionts. It also appears that the antibiotic characteristic is dependent on many factors, i.e., the algae strain, the microorganisms, the season and the growth condition [64, 65, 66, 67]. Several extractable compounds, for instance, cyclic polysulfides and halogenated compounds, are toxic to microorganisms and, therefore, responsible for the antibiotic activity of some marine algae [68, 69, 70].
2.9.1. Antibacterial activity of cyanobacteria
Cyanobacteria are phototrophic organisms with a classic prokaryotic cell organization, but similar to eukaryotes they conduct photosynthesis and respiration in their active membrane system [71]. Microalgae grow ubiquitously and produce, in addition to toxins, a wide range of bioactive metabolites with potential application in biotechnology [72]. These characteristics have made them the focus of intense examination in the last decade [73, 74].
To date, only a few compounds have been extracted and commercialized, including nutraceuticals, cosmetic products and other high-value molecules [39, 75]. Some purified compounds have promising commercial applications as bioplastics, biofertilizers, antiviral, antifungal, anticancer and antibacterial drugs [76, 77, 78]. Table 3 illustrates some examples of antibacterial, antifungal and antimycobacterial compounds extracted from cyanobacteria.
Table 3.
Antibacterial compounds extracted from microalgae.
The production of bioactive compounds from cyanobacteria has received more attention than from eukaryotic microalgae. The reason may be probably based on the simpler culture methods available for cyanobacteria growth, and also to their greater resistance to bacterial contamination [89]. Nevertheless, more and more studies have recently focused on the synthesis of bioactive compounds, such as isoprenoids, polyketides, no ribosomal peptides, polyunsaturated fatty acids and alkaloids, by eukaryotic microalgae [90], used to inhibit bacterial activity [6, 91, 92]. In addition, further studies have identified fatty acids, terpenes, carbohydrates, glycolipids, lipoproteins, bromophenols and tannins, among other, as compounds that exhibit antibacterial activity against human pathogens [93, 94].
Microalgae accumulate cell-associated antibacterial substances [95, 96], and some studies have shown different levels of antibacterial activity in different microalgae cultures [95, 97, 98, 99]. Moreover, crude extracts from different species of eukaryotic microalgae have shown effectiveness against both Gram positive (Gram+) and Gram negative (Gram−) bacteria, as well as Mycobacterium tuberculosis [100, 101, 102, 103, 104]. This could suggest, therefore, the potential of microalgae for the production of compounds with a broad-spectrum activity, which is highly desired for the production of new antibiotics. However, many compounds extracted from these organisms are likely to be impractical as antibiotics for medical uses as a result of, for instance, its toxicity or inactivity in vivo [61]. Table 4 presents a summary of the eukaryotic microalgae with the highest antibacterial activity or the widest spectrum of activity of large screening programs to date.
Cyanobacteria and microalgae have demonstrated a large potential as innovative sources of a large variety of bioactive compounds, such as fatty acids, antioxidants, antifreeze proteins and even antibiotics. While the characterization of substances as fatty acids is relatively well-established and straightforward, an information gap still remains in the elucidation of structures of antibiotics. Despite the fact that a variety of extracts obtained from microalgae biomass have demonstrated a clear antibiotic capacity, the structure of the molecules involved in the observed activity still remains unclear. There is a clear and almost unrevealed potential in the development of innovative nutraceutical and pharmaceutical industries based on cultivation of microalgae and cyanobacteria and their exploitation in the production of bioactive substances. Cyanobacteria and microalgae adapted to extreme environments for sure have an enormous potential that thorough bioprospecting approaches can help to unveil.
The authors certify that they have no conflict of interest.
References
1.Barsanti L, Coltelli P, Evangelista V, Frassanito AM, Passarelli V, Vesentini N, Gualtieri P. Oddities and curiosities in the algal world. In: Algal Toxins: Nature, Occurrence, Effect and Detection. Pisa, Italy: Springer; 2008. pp. 353-391
2.Apt KE, Behrens PW. Commercial developments in microalgal biotechnology. Journal of Phycology. 1999;35:215-226
3.Luiten EE, Akkerman I, Koulman A, Kamermans P, Reith H, Barbosa MJ, Sipkema D, Wijffels RH. Realizing the promises of marine biotechnology. Biomolecular Engineering. 2003;20:429-439
4.Yamaguchi K. Recent advances in microalgal bioscience in Japan, with special reference to utilization of biomass and metabolites: A review. Journal of Applied Phycology. 1996;8:487-502
5.Spoehr H, Milner HW. The chemical composition of Chlorella: Effect of environmental conditions. Plant Physiology. 1949;24:120
6.Burja AM, Banaigs B, Abou-Mansour E, Burgess JG, Wright PC. Marine cyanobacteria—A prolific source of natural products. Tetrahedron. 2001;57:9347-9377
7.Maschek JA, Baker BJ. The chemistry of algal secondary metabolism. Algal Chemical Ecology. Berlin, Heidelberg: Springer-Verlag; 2008:1-24
8.Sang M, Wang M, Liu J, Zhang C, Li A. Effects of temperature, salinity, light intensity, and pH on the eicosapentaenoic acid production of Pinguiococcus pyrenoidosus. Journal of Ocean University of China (English Edition). 2012;11:181-186
9.Breuer G, Lamers PP, Martens DE, Draaisma RB, Wijffels RH. Effect of light intensity, pH, and temperature on triacylglycerol (TAG) accumulation induced by nitrogen starvation in Scenedesmus obliquus. Bioresource Technology. 2013;143:1-9
10.Juneja A, Ceballos RM, Murthy GS. Effects of environmental factors and nutrient availability on the biochemical composition of algae for biofuels production: A review. Energies. 2013;6:4607-4638
11.Skjånes K, Rebours C, Lindblad P. Potential for green microalgae to produce hydrogen, pharmaceuticals and other high value products in a combined process. Critical Reviews in Biotechnology. 2013;33:172-215
12.Carmichael W. Cyanobacteria secondary metabolites—The cyanotoxins. Journal of Applied Microbiology. 1992;72:445-459
13.Leflaive J, Ten-Hage L. Algal and cyanobacterial secondary metabolites in freshwaters: A comparison of allelopathic compounds and toxins. Freshwater Biology. 2007;52:199-214
14.Malik V. Microbial secondary metabolism. Trends in Biochemical Sciences. 1980;5:68-72
15.Senhorinho GNA, Ross GM, Scott JA. Cyanobacteria and eukaryotic microalgae as potential sources of antibiotics. Phycologia. 2015;54:271-282
16.Rosenberg JN, Oyler GA, Wilkinson L, Betenbaugh MJ. A green light for engineered algae: Redirecting metabolism to fuel a biotechnology revolution. Current Opinion in Biotechnology. 2008;19:430-436
17.Granot E, Kohen R. Oxidative stress in childhood—In health and disease states. Clinical Nutrition. 2004;23:3-11
18.Guerin M, Huntley ME, Olaizola M. Haematococcus astaxanthin: Applications for human health and nutrition. Trends in Biotechnology. 2003;21:210-216
19.Pham-Huy LA, He H, Pham-Huy C. Free radicals, antioxidants in disease and health. International Journal of Biomedical Science. 2008;4:89
20.Borowitzka M. Vitamins and Fine Chemicals from Micro-Algae. Cambridge University Press; 1988
21.Babu B, Wu JT. Production of natural butylated hydroxytoluene as an antioxidant by freshwater phytoplankton. Journal of Phycology. 2008;44:1447-1454
22.Duval B, Shetty K, Thomas WH. Phenolic compounds and antioxidant properties in the snow alga Chlamydomonas nivalis after exposure to UV light. Journal of Applied Phycology. 1999;11:559-566
23.Becker W. 18 microalgae in human and animal nutrition. In: Handbook of Microalgal Culture: Biotechnology and Applied Phycology. Oxford, UK: Blackwell Science Ltd; 2004. p. 312
24.Running J, Severson D, Schneider K. Extracellular production of L-ascorbic acid by Chlorella protothecoides, Prototheca species, and mutants of P. moriformis during aerobic culturing at low pH. Journal of Industrial Microbiology & Biotechnology. 2002;29:93-98
25.Cha KH, Koo SY, Lee D-U. Antiproliferative effects of carotenoids extracted from Chlorella ellipsoidea and Chlorella vulgaris on human colon cancer cells. Journal of Agricultural and Food Chemistry. 2008;56:10521-10526
26.Leya T, Rahn A, Lütz C, Remias D. Response of arctic snow and permafrost algae to high light and nitrogen stress by changes in pigment composition and applied aspects for biotechnology. FEMS Microbiology Ecology. 2009;67:432-443
27.Hu Q, Sommerfeld M, Jarvis E, Ghirardi M, Posewitz M, Seibert M, Darzins A. Microalgal triacylglycerols as feedstocks for biofuel production: Perspectives and advances. The Plant Journal. 2008;54:621-639
28.Yongmanitchai W, Ward OP. Omega-3 fatty acids: alternative sources of production. Process Biochemistry. 1989;24:117-125
29.Simopoulos AP. Essential fatty acids in health and chronic disease. The American Journal of Clinical Nutrition. 1999;70:560s-569s
30.Ben-Amotz A, Tornabene TG, Thomas WH. Chemical profile of selected species of microalgae with emphasis on lipids. Journal of Phycology. 1985;21:72-81
31.Chiang IZ, Huang WY, Wu JT. Allelochemicals of Botryococcus braunii (chlorophyceae). Journal of Phycology. 2004;40:474-480
32.Poerschmann J, Spijkerman E, Langer U. Fatty acid patterns in Chlamydomonas sp. as a marker for nutritional regimes and temperature under extremely acidic conditions. Microbial Ecology. 2004;48:78-89
33.Seto A, Wang H, Hesseltine C. Culture conditions affect eicosapentaenoic acid content of Chlorella minutissima. Journal of the American Oil Chemists' Society. 1984;61:892-894
34.Ahlgren G, Gustafsson IB, Boberg M. Fatty acid content and chemical composition of freshwater microalgae. Journal of Phycology. 1992;28:37-50
35.Mohamed ZA. Polysaccharides as a protective response against microcystin-induced oxidative stress in Chlorella vulgaris and Scenedesmus quadricauda and their possible significance in the aquatic ecosystem. Ecotoxicology. 2008;17:504
36.Guzman S, Gato A, Lamela M, Freire-Garabal M, Calleja J. Anti-inflammatory and immunomodulatory activities of polysaccharide from Chlorella stigmatophora and Phaeodactylum tricornutum. Phytotherapy Research. 2003;17:665-670
37.Sheng J, Yu F, Xin Z, Zhao L, Zhu X, Hu Q. Preparation, identification and their antitumor activities in vitro of polysaccharides from Chlorella pyrenoidosa. Food Chemistry. 2007;105:533-539
38.Iwamoto H. Industrial production of microalgal cell-mass and secondary products-major industrial species. In: Handbook of Microalgal Culture: Biotechnology and Applied Phycology. Oxford, UK: Blackwell Science Ltd; 2004. p. 255
39.Spolaore P, Joannis-Cassan C, Duran E, Isambert A. Commercial applications of microalgae. Journal of Bioscience and Bioengineering. 2006;101:87-96
40.León R, Galván F. Interaction between saline stress and photoinhibition of photosynthesis in the freshwater green algae Chlamydomonas reinhardtii. Implications for glycerol photoproduction. Plant Physiology and Biochemistry. 1999;37:623-628
41.Miyasaka H, Ohnishi Y, Akano T, Fukatsu K, Mizoguchi T, Yagi K, Maeda I, Ikuta Y, Matsumoto H, Shioji N. Excretion of glycerol by the marine Chlamydomonas sp. strain W-80 in high CO2 cultures. Journal of Fermentation and Bioengineering. 1998;85:122-124
42.Wang Z, Zhuge J, Fang H, Prior BA. Glycerol production by microbial fermentation: A review. Biotechnology Advances. 2001;19:201-223
43.Ahmad I, Hellebust JA. The role of glycerol and inorganic ions in osmoregulatory responses of the euryhaline flagellate Chlamydomonas pulsatilla Wollenweber. Plant Physiology. 1986;82:406-410
44.Hadi M, Shariati M, Afsharzadeh S. Microalgal biotechnology: Carotenoid and glycerol production by the green algae Dunaliella isolated from the Gave-Khooni salt marsh, Iran. Biotechnology and Bioprocess Engineering. 2008;13:540-544
45.Ördög V, Stirk W, Lenobel R, Bancířová M, Strnad M, Van Staden J, Szigeti J, Németh L. Screening microalgae for some potentially useful agricultural and pharmaceutical secondary metabolites. Journal of Applied Phycology. 2004;16:309-314
46.Abedin RM, Taha HM. Antibacterial and antifungal activity of cyanobacteria and green microalgae. Evaluation of medium components by Plackett-Burman design for antimicrobial activity of Spirulina platensis. Global Journal of Biotechnology and Biochemistry. 2008;3:22-31
47.Chu C, Liao W, Huang R, Lin L. Haemagglutinating and antibiotic activities of freshwater microalgae. World Journal of Microbiology and Biotechnology. 2004;20:817-825
48.Shon Y-H, Nam K-S, Kim M-K. Cancer chemopreventive potential of Scenedesmus spp. cultured in medium containing bioreacted swine urine. Journal of Microbiology and Biotechnology. 2004;14:158-161
49.Liao W-R, Lin J-Y, Shieh W-Y, Jeng W-L, Huang R. Antibiotic activity of lectins from marine algae against marine vibrios. Journal of Industrial Microbiology and Biotechnology. 2003;30:433-439
50.Karsten U, Lembcke S, Schumann R. The effects of ultraviolet radiation on photosynthetic performance, growth and sunscreen compounds in aeroterrestrial biofilm algae isolated from building facades. Planta. 2007;225:991-1000
51.Xiong F, Kopecky J, Nedbal L. The occurrence of UV-B absorbing mycosporine-like amino acids in freshwater and terrestrial microalgae (Chlorophyta). Aquatic Botany. 1999;63:37-49
52.Schmid D, Schürch C, Zülli F. Mycosporine-like amino acids from red algae protect against premature skin-aging. Euro Cosmetics. 2006;9:1-4
53.Hasegawa T, Matsuguchi T, Noda K, Tanaka K, Kumamoto S, Shoyama Y, Yoshikai Y. Toll-like receptor 2 is at least partly involved in the antitumor activity of glycoprotein from Chlorella vulgaris. International Immunopharmacology. 2002;2:579-589
54.Tanaka K, Yamada A, Noda K, Hasegawa T, Okuda M, Shoyama Y, Nomoto K. A novel glycoprotein obtained from Chlorella vulgaris strain CK22 shows antimetastatic immunopotentiation. Cancer Immunology, Immunotherapy. 1998;45:313-320
55.Fujii Y, Sakamoto S, Ben-Amotz A, Nagasawa H. Effects of beta-carotene-rich algae Dunaliella bardawil on the dynamic changes of normal and neoplastic mammary cells and general metabolism in mice. Anticancer Research. 1993;13:389-393
56.Christner BC. Bioprospecting for microbial products that affect ice crystal formation and growth. Applied Microbiology and Biotechnology. 2010;85:481-489
57.Fernandes BD, Dragone GM, Teixeira JA, Vicente AA. Light regime characterization in an airlift photobioreactor for production of microalgae with high starch content. Applied Biochemistry and Biotechnology. 2010;161:218-226
58.Kang J-S, Raymond JA. Reduction of freeze-thaw-induced hemolysis of red blood cells by an algal ice-binding protein. CryoLetters. 2004;25:307-310
59.Lustigman B. Comparison of antibiotic production from four ecotypes of the marine alga, Dunaliella. Bulletin of Environmental Contamination and Toxicology. 1988;40:18-22
60.Ghazala B, Shameel M, Choudhary MI, Shahzad S, Leghari SM. Phycochemistry and bioactivity of Tetraspora (volvocophyta) from Sindh. Pakistan Journal of Botany. 2004;36:531-548
61.Borowitzka MA. Microalgae as sources of pharmaceuticals and other biologically active compounds. Journal of Applied Phycology. 1995;7:3-15
62.Berdy J. The discovery of new bioactive microbial metabolites: screening and identification. Progress in Industrial Microbiology. 1989;27:3-27
63.Smith A. Modes of cyanobacterial carbon metabolism. In: Annales De l'Institut Pasteur/Microbiologie. Elsevier; 1983. pp. 93-113
64.Centeno POR, Ballantine DL. Effects of culture conditions on production of antibiotically active metabolites by the marine alga Spyridia filamentosa (Ceramiaceae, Rhodophyta). I. Light. Journal of Applied Phycology. 1998;10:453
65.Hornsey I, Hide D. The production of antimicrobial compounds by British marine algae. I. Antibiotic-producing marine algae. British Phycological Journal. 1974;9:353-361
66.Hornsey I, Hide D. The production of antimicrobial compounds by British marine algae. II. Seasonal variation in production of antibiotics. British Phycological Journal. 1976;11:63-67
67.Pesando D, Caram B. Screening of marine algae from the French Mediterranean Coast for antibacterial and antifungal activity. Botanica Marina. 1984;27:381-386
68.Norris JN, Fenical W. Chemical defense in tropical marine algae. In: The Atlantic Barrier Reef Ecosystem at Carrie Bow Cay, Belize. Vol. 1. Washington, USA: Smithsonian Institution press; 1982. pp. 417-431
69.Ohta K. Chemical studies on biologically active substances in seaweeds. In: Proceedings of the International Seaweed Symposium; 1979. pp. 401-411
70.Wratten SJ, Faulkner DJ. Cyclic polysulfides from the red alga Chondria californica. The Journal of Organic Chemistry. 1976;41:2465-2467
71.Singh RK, Tiwari SP, Rai AK, Mohapatra TM. Cyanobacteria: An emerging source for drug discovery. The Journal of Antibiotics. 2011;64:401-412
72.Bloor S, England RR. Antibiotic production by the cyanobacterium Nostoc muscorum. Journal of Applied Phycology. 1989;1:367-372
73.Dahms H-U, Ying X, Pfeiffer C. Antifouling potential of cyanobacteria: A mini-review. Biofouling. 2006;22:317-327
74.Wijffels RH, Kruse O, Hellingwerf KJ. Potential of industrial biotechnology with cyanobacteria and eukaryotic microalgae. Current Opinion in Biotechnology. 2013;24:405-413
75.Borowitzka MA. High-value products from microalgae—Their development and commercialisation. Journal of Applied Phycology. 2013;25:743-756
76.Patterson GM, Larsen LK, Moore RE. Bioactive natural products from blue-green algae. Journal of Applied Phycology. 1994;6:151-157
77.Abed RM, Dobretsov S, Sudesh K. Applications of cyanobacteria in biotechnology. Journal of Applied Microbiology. 2009;106:1-12
78.Leão PN, Costa M, Ramos V, Pereira AR, Fernandes VC, Domingues VF, Gerwick WH, Vasconcelos VM, Martins R. Antitumor activity of hierridin B, a cyanobacterial secondary metabolite found in both filamentous and unicellular marine strains. PLoS One. 2013;8:e69562
79.Swain SS, Paidesetty SK, Padhy RN. Antibacterial, antifungal and antimycobacterial compounds from cyanobacteria. Biomedicine & Pharmacotherapy. 2017;90:760-776
80.Falch BS, Koenig GM, Wright AD, Sticher O, Ruegger H, Bernardinelli G. Ambigol A and B: new biologically active polychlorinated aromatic compounds from the terrestrial blue-green alga Fischerella ambigua. The Journal of Organic Chemistry. 1993;58:6570-6575
81.Mo S, Krunic A, Santarsiero BD, Franzblau SG, Orjala J. Hapalindole-related alkaloids from the cultured cyanobacterium Fischerella ambigua. Phytochemistry. 2010;71:2116-2123
82.Raveh A, Carmeli S. Antimicrobial ambiguines from the cyanobacterium Fischerella sp. collected in Israel. Journal of Natural Products. 2007;70:196-201
83.Mo S, Krunic A, Chlipala G, Orjala J. Antimicrobial ambiguine isonitriles from the cyanobacterium Fischerella ambigua. Journal of Natural Products. 2009;72:894-899
84.Berry JP, Gantar M, Gawley RE, Wang M, Rein KS. Pharmacology and toxicology of pahayokolide A, a bioactive metabolite from a freshwater species of Lyngbya isolated from the Florida Everglades. Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology. 2004;139:231-238
85.Ishida K, Matsuda H, Murakami M, Yamaguchi K. Kawaguchipeptin B, an antibacterial cyclic undecapeptide from the cyanobacterium Microcystis aeruginosa. Journal of Natural Products. 1997;60:724-726
86.Jaki B, Orjala J, Bürgi H-R, Sticher O. Biological screening of cyanobacteria for antimicrobial and molluscicidal activity, brine shrimp lethality, and cytotoxicity. Pharmaceutical Biology. 1999;37:138-143
87.Jaki B, Heilmann J, Sticher O. New antibacterial metabolites from the Cyanobacterium Nostoc commune (EAWAG 122b). Journal of Natural Products. 2000;63:1283-1285
88.Ploutno A, Carmeli S. Nostocyclyne A, a novel antimicrobial cyclophane from the cyanobacterium Nostoc sp. Journal of Natural Products. 2000;63:1524-1526
89.Deschênes J-S, Boudreau A, Tremblay R. Mixotrophic production of microalgae in pilot-scale photobioreactors: Practicability and process considerations. Algal Research. 2015;10:80-86
90.Sasso S, Pohnert G, Lohr M, Mittag M, Hertweck C. Microalgae in the postgenomic era: A blooming reservoir for new natural products. FEMS Microbiology Reviews. 2012;36:761-785
91.Costa M, Costa-Rodrigues J, Fernandes MH, Barros P, Vasconcelos V, Martins R. Marine cyanobacteria compounds with anticancer properties: A review on the implication of apoptosis. Marine Drugs. 2012;10:2181-2207
92.Gupta V, Ratha SK, Sood A, Chaudhary V, Prasanna R. New insights into the biodiversity and applications of cyanobacteria (blue-green algae)—Prospects and challenges. Algal Research. 2013;2:79-97
93.Stein JR, Borden CA. Causative and beneficial algae in human disease conditions: A review. Phycologia. 1984;23:485-501
94.Metting B, Pyne JW. Biologically active compounds from microalgae. Enzyme and Microbial Technology. 1986;8:386-394
95.Cooper S, Battat A, Marsot P, Sylvestre M. Production of antibacterial activities by two Bacillariophyceae grown in dialysis culture. Canadian Journal of Microbiology. 1983;29:338-341
96.Cannell RJ, Owsianka AM, Walker JM. Results of a large-scale screening programme to detect antibacterial activity from freshwater algae. British Phycological Journal. 1988;23:41-44
97.Pratt R, Daniels T, Eiler JJ, Gunnison J, Kumler W, Oneto JF, Strait LA, Spoehr H, Hardin G, Milner H. Chlorellin, an antibacterial substance from Chlorella. Science (Washington). 1944:351-352
98.Hansen JA. Antibiotic activity of the chrysophyte Ochromonas malhamensis. Physiologia Plantarum. 1973;29:234-238
99.Kokou F, Makridis P, Kentouri M, Divanach P. Antibacterial activity in microalgae cultures. Aquaculture Research. 2012;43:1520-1527
100.Prakash S, Bhimba BV. Pharmaceutical development of novel microalgal compounds for Mdr Mycobacterium tuberculosis. CSIT. 2005;4(4):264-269
101.Desbois AP, Mearns-Spragg A, Smith VJ. A fatty acid from the diatom Phaeodactylum tricornutum is antibacterial against diverse bacteria including multi-resistant Staphylococcus aureus (MRSA). Marine Biotechnology. 2009;11:45-52
102.Arun N, Gupta S, Singh D. Antimicrobial and antioxidant property of commonly found microalgae Spirulina platensis, Nostoc muscorum and Chlorella pyrenoidosa against some pathogenic bacteria and fungi. International Journal of Pharmaceutical Sciences and Research. 2012;3:4866
103.Bai VDM, Krishnakumar S. Evaluation of antimicrobial metabolites from marine microalgae Tetraselmis suecica using gas chromatography-mass spectrometry (GC–MS) analysis. International Journal of Pharmacy and Pharmaceutical Sciences. 2013;5:17-23
104.Danyal A, Mubeen U, Malik KA. Investigating two native algal species to determine antibiotic susceptibility against some pathogens. Current Research Journal of Biological Sciences. 2013;5:70-74
105.Falaise C, François C, Travers M-A, Morga B, Haure J, Tremblay R, Turcotte F, Pasetto P, Gastineau R, Hardivillier Y. Antimicrobial compounds from eukaryotic microalgae against human pathogens and diseases in aquaculture. Marine Drugs. 2016;14:159
106.Ghasemi Y, Moradian A, Mohagheghzadeh A, Shokravi S, Morowvat MH. Antifungal and antibacterial activity of the microalgae collected from paddy fields of Iran: Characterization of antimicrobial activity of Chroococcus dispersus. Journal of Biological Science. 2007;7(6):904-910
107.Chang T, Ohta S, Ikegami N, Miyata H, Kashimoto T, Kondo M. Antibiotic substances produced by a marine green alga, Dunaliella primolecta. Bioresource Technology. 1993;44:149-153
108.Ohta S, Chang T, Ikegami N, Kondo M, Miyata H. Antibiotic substance produced by a newly isolated marine microalga, Chlorococcum HS-101. Bulletin of Environmental Contamination and Toxicology. 1993;50:171-178
109.Ohta S, Shiomi Y, Kawashima A, Aozasa O, Nakao T, Nagate T, Kitamura K, Miyata H. Antibiotic effect of linolenic acid from Chlorococcum strain HS-101 and Dunaliella primolecta on methicillin-resistant Staphylococcus aureus. Journal of Applied Phycology. 1995;7:121-127
110.Bhagavathy S, Sumathi P, Bell IJS. Green algae Chlorococcum humicola—A new source of bioactive compounds with antimicrobial activity. Asian Pacific Journal of Tropical Biomedicine. 2011;1:S1-S7
111.Pane G, Cacciola G, Giacco E, Mariottini GL, Coppo E. Assessment of the antimicrobial activity of algae extracts on bacteria responsible of external otitis. Marine Drugs. 2015;13:6440-6452
112.Herrero M, Ibanez E, Cifuentes A, Reglero G, Santoyo S. Dunaliella salina microalga pressurized liquid extracts as potential antimicrobials. Journal of Food Protection. 2006;69:2471-2477
113.Mendiola JA, Santoyo S, Cifuentes A, Reglero G, Ibanez E, Señoráns FJ. Antimicrobial activity of sub-and supercritical CO2 extracts of the green alga Dunaliella salina. Journal of Food Protection. 2008;71:2138-2143
114.Rodríguez-Meizoso I, Jaime L, Santoyo S, Señoráns F, Cifuentes A, Ibáñez E. Subcritical water extraction and characterization of bioactive compounds from Haematococcus pluvialis microalga. Journal of Pharmaceutical and Biomedical Analysis. 2010;51:456-463
115.Santoyo S, Rodríguez-Meizoso I, Cifuentes A, Jaime L, Reina GG-B, Señorans FJ, Ibáñez E. Green processes based on the extraction with pressurized fluids to obtain potent antimicrobials from Haematococcus pluvialis microalgae. LWT - Food Science and Technology. 2009;42:1213-1218
116.Mudimu O, Rybalka N, Bauersachs T, Born J, Friedl T, Schulz R. Biotechnological screening of microalgal and cyanobacterial strains for biogas production and antibacterial and antifungal effects. Metabolites. 2014;4:373-393
117.Catarina Guedes A, Barbosa CR, Amaro HM, Pereira CI, Xavier Malcata F. Microalgal and cyanobacterial cell extracts for use as natural antibacterial additives against food pathogens. International Journal of Food Science and Technology. 2011;46:862-870
118.Najdenski HM, Gigova LG, Iliev II, Pilarski PS, Lukavský J, Tsvetkova IV, Ninova MS, Kussovski VK. Antibacterial and antifungal activities of selected microalgae and cyanobacteria. International Journal of Food Science and Technology. 2013;48:1533-1540
119.Viso A, Pesando D, Baby C. Antibacterial and antifungal properties of some marine diatoms in culture. Botanica Marina. 1987;30:41-46
120.Ingebrigtsen RA, Hansen E, Andersen JH, Eilertsen HC. Light and temperature effects on bioactivity in diatoms. Journal of Applied Phycology. 2016;28:939-950
121.Sánchez-Saavedra M, Licea-Navarro A, Bernáldez-Sarabia J. Evaluation of the antibacterial activity of different species of phytoplankton. Revista de Biología Marina y Oceanografía. 2010;45(3):531-536
122.Mendiola JA, Torres CF, Toré A, Martín-Álvarez PJ, Santoyo S, Arredondo BO, Señoráns FJ, Cifuentes A, Ibáñez E. Use of supercritical CO2 to obtain extracts with antimicrobial activity from Chaetoceros muelleri microalga. A correlation with their lipidic content. European Food Research and Technology. 2007;224:505-510
123.Findlay JA, Patil AD. Antibacterial constituents of the diatom Navicula delognei. Journal of Natural Products. 1984;47:815-818
124.Scepankova H, Saraiva JA, Estevinho LM. Honey health benefits and uses in medicine. In: Bee Products-Chemical and Biological Properties. Springer; 2017. pp. 83-96
125.Desbois AP, Lebl T, Yan L, Smith VJ. Isolation and structural characterisation of two antibacterial free fatty acids from the marine diatom, Phaeodactylum tricornutum. Applied Microbiology and Biotechnology. 2008;81:755-764
126.Venkatesan R, Karthikayen R, Periyanayagi R, Sasikala V, Balasubramanian T. Antibacterial activity of the marine diatom, Rhizosolenia alata (Brightwell, 1858) against human pathogens. Research Journal of Microbiology. 2007;2:98-100
127.Duff D, Bruce D, Antia N. The antibacterial activity of marine planktonic algae. Canadian Journal of Microbiology. 1966;12:877-884
128.Bruce D, Duff D, Antia N. The identification of two antibacterial products of the marine planktonic alga Isochrysis galbana. Microbiology. 1967;48:293-298
Written By
Elena Martínez-Francés and Carlos Escudero-Oñate
Submitted: 19 October 2017Reviewed: 15 January 2018Published: 07 March 2018
Open access peer-reviewed chapter
