Production of Primary and Secondary Metabolites Using Algae

  • Milagros Rico
  • Aridane G. González
  • Magdalena Santana-Casiano
  • Melchor González-Dávila
  • Norma Pérez-Almeida
  • Miguel Suarez de Tangil
Chapter

Abstract

Over the past few decades, there has been an increase in the number of research studies focused on all aspects of the ecology, physiology, biochemistry, cell biology, molecular biology, systematics and uses of algae. This chapter will provide an overview of the potential human health advantages associated with the use of algae as a source of high-value products, especially focused on those metabolites with biological activities and potential therapeutic applications in the pharmaceutical and food industries. Moreover, the production of polyphenols by marine microalgae will be also considered, as well their impact on the biogeochemical cycles of trace metals and the phytoplankton implications. These data will support as a baseline for future research in wastewater and marine environments.

1 Introduction

The interest of algae, cyanobacteria, and microalgae increased in the last decades, achieving a total number of publications of 3,586 (the 1960s) and 56,313 in the 2000s (Fig. 1), according to Scopus database. This increase is due to several factors: improvement of technology, the increased demand for healthy and functional foods, pharmacological properties of algal metabolites for disease prevention and treatment and, algae biofuels research in order to provide a viable alternative to fossil fuels, among many others.
Fig. 1

Evolution of the number of scientific documents reported per decade

The main subject areas in which these documents are issued within the last three decades are Agricultural and Biological Sciences, Biochemistry, Genetics and Molecular Biology, Environmental and Planetary Sciences and Earth and Planetary Sciences (Fig. 2). The percentage of scientific publications reaches values as high as 36.2% (2001–2010), 42.0% (1991–2000), and 46.4% (1981–1990) when subject areas related to human and animal health sciences are considered. Within these areas, we can find toxicology, cell and molecular biology, biomedical research, basic clinical and pharmaceutical microbiology, pharmaceutical biotechnology, medicinal chemistry, phytochemistry, and nutraceuticals.
Fig. 2

Percentages of documents per subject area according to Scopus database

The extensive research on extracting drugs from the sea organisms began in the mid-1970s. Since 1975, the reported applications of these drugs isolated from algae are numerous (Priyadarshani and Rath 2012). These studies have clearly demonstrated that algae represent valuable sources of a wide variety of compounds with different potential applications in food, cosmetic and pharmaceutical industries (Li et al. 2014; Machu et al. 2015). Developing new technologies after the 1980s has led to extract new metabolites from algae cultures and to determine the chemical structure of 15,000 novel compounds, decreasing the biomass needed from kilograms to grams (Borowitzka 1995). This also makes possible to increase the number of newly studied species, especially for microalgae.

Algae range from unicellular organisms such as diatoms to seaweeds extending over 30 m long. Diatoms have been widely investigated because they are a diverse group of microalgae (250 orders and more than 105 species) and the sole ones with a siliceous cell wall (Norton et al. 1996). Diatoms contribute as much as 25% of the global primary productivity (Scala and Bowler 2001). A high variety of phytoplankton species has been described (40,000 species), being 680 species of marine algae divided in Rhodophyta, Phaeophyta, Chlorophyta (Boopathy and Kathiresan 2010).

Marine algae can be considered an arsenal of metabolites with pharmaceutical potential, including anticancer, antitumor, antioxidant, antiobesity, neuroprotective, antimicrobial, antinociceptive, anti-inflammatory, and antiangiogenic activities (Cornish and Garbary 2010; Gupta and Abu-Ghannam 2011; Pangestuti and Kim 2011). Microalgae are able to produce highly bioactive compounds extracted from the marine environments (Shimizu 1996). The antibacterial activity of substances excreted by an aquatic microalga was first reported for Chlorella vulgaris (Pratt and Fong 1940). Currently, algae have attracted attention because they are biological systems capable of using solar energy to produce a large number of active metabolites via the photosynthetic process with the highest efficiency (Shalaby 2011). Blue-green algae produce a number of highly active antitumor compounds (Shimizu 2000).

The focus in this chapter is placed on the main classes of algal metabolites that could be of medicinal, nutritional and pharmaceutical value. Seaweeds may become a suitable natural source of bioactive compounds reported to possess strong antiviral, antitumor and anticancer properties, among others. Here, we discuss the pharmaceutical, health and research potential of different primary and secondary metabolites present in algae, with a focus on those from microalgae and paying special attention to the polyphenolic compounds and the involvement of these compounds in protection cell mechanisms in conditions of mental stress.

2 Primary Metabolites

Primary metabolism represents an essential biogeochemical pathway directly involved in cell growth and reproduction. The most important primary metabolites are carbohydrates, lipids, and proteins (Wen et al. 2015).

Lipids

Lipids content of algal cells can achieve 90% of dry weight (Metting et al. 1996). These lipids consist in phospholipids, glycolipids, non-polar glycerolipids, saturated and unsaturated fatty acids (PUFA) (Kumari et al. 2013). Within the group of PUFA, linolenic acid, eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid have great interest for many diseases as cancer, cardiovascular, diabetes, inflammatory, asthma, etc. (Andersen et al. 2008; Priyadarshani and Rath 2012).

Crude lipids have been extracted from a wide group of algal species (Laurencia popillose, Galaxoura cylindriea, Ulva fasciata, Taonia atomaria, and Dilophys fasciola), but the group of Dunaliella, Chlorella, and Spirulina species are the most interesting in terms of high concentration of lipids (El Baz et al. 2002; Abd El Baky et al. 2014a, b). On the other hand, Phaeodactylum tricornutum (marine diatom) is also considered the main producer of eicosapentaenoic acid (EPA) (Grima et al. 2003) and Nitzschia inconspicua (marine diatom) produces high levels of arachidonic acid, an essential polyunsaturated fatty acid (Chu et al. 1994) under deficiency in linoleic acid.

In general, crude lipids of several algal species such as Laurencia popillose, Galaxoura cylindriea, Ulva fasciata, Taonia atomaria, and Dilophys fasciola) showed different biological properties as antitumor, antioxidant, antimicrobial and antivirus with various degrees (Abd El Baky et. 2014a, b; Ghazala et al. 2010). PUFA microalgae-derived such as γ-linolenic acid, arachidonic acid, EPA and docosahexaenoic acid (DHA) are widely used as nutritional supplements, pharmaceutical, and functional food and their roles in promoting human health have been extensively studied (Borowitzka 2013; Michalak and Chojnacka 2015; Priyadarshani and Rath 2012).

Polyunsaturated fatty acids, phenolic and flavonoids from T. atomaria and L. papillose have shown an inhibitory effect against human hepatocarcinoma and human breast carcinoma. These complex lipids are usually rare in terrestrial plants but are present in relatively large amounts in some species of marine algae (Abd El Baky et al. 2014a, b; Castro et al. 2016; Harwood and Guschina 2009).

Proteins

Marine algae have high protein content, up to 70% of the dry weight, depending on the season and the species (Abreu et al. 2014; Fan et al. 2014). According to Becker (2007), Arthrospira maxima (cyanobacteria with 60–71% proteins) is one of the most important microalgae in this sense. Currently, marine algae proteins have attracted great interest as a source of bioactive peptides for therapeutic uses (Kim and Kang 2011). Several studies have isolated various algal peptides possessing anti-infective activities (Kang et al. 2015a, b). Depending on the amino acid sequence, biopeptides isolated from marine algae may be associated with different biological functions, including antioxidant, anticancer, antihypertensive, anti-atherosclerotic, and immunomodulatory effects (Fan et al. 2014).

Carbohydrates

Carbohydrates can be found as glucose, sugars and other polysaccharides in microalgae, making relevant the production of carbohydrates because of their high overall digestibility (Becker 2004). In this sense, carbohydrates compounds may achieve from 10% (Scenedesmus obliquus) to 57% (Porphyridium cruentum) of dry biomass (Becker 2004).

Among marine biologically active metabolites, polyphenols and polysaccharides have shown more effective antioxidant and anticancer activities (Farvin and Jacobsen 2013; Li et al. 2014). In the last decades, the study of polysaccharides from marine algae has gained renewed interest for their many valuable biological properties and therapeutic applications (Barahona et al. 2014; Kang et al. 2015a, b). Hossain et al. (2005) suggested that algal glycolipids such as digalactosyl diacylglycerol and sulfoquinovosyl diacylglycerol combined with sodium butyrate might be used as potential colon cancer chemotherapy agents. Spirulina platensis accumulate a high amount of sulfated polysaccharides with biological activities as an anticoagulant, anticancer, antiviral, antimicrobial, and antioxidant (Abd El Baky et al. 2013). In addition, red algae are important sources of sulfated polysaccharides which show antiviral activities in human infectious diseases by viruses (Damonte et al. 1994; Witvrouw et al. 1994). The inhibitory effect is mostly due to the interaction with the positive charges on the viruses cell surfaces, preventing the penetration into the host cells (Ehresmann et al. 1979) Aghardhiella tenera and Nothogenia fastigiata are characteristics because of their capacity to produce polysaccharides with low cytoxoxic activities (de Clercq 1996). Another important use of polysaccharides is the antiviral action against two enveloped rhabdovirusees with high economic impacts, such as hemorrhagic septicemia virus and the African swine fever virus. Some algal polysaccharides and fibers are also able to reduced cholesterol absorption in the gut, such as alginate, carrageenan, funoran, fucoidan, laminaran, porphyrin and ulvan (Kiriyama et al. 1969; Lamela et al. 1989; Panlasigui et al. 2003). Accordingly, the production of polysaccharides seems to be a potential industrial option against viral therapy.

Several reviews focused on algae-derived polysaccharides (alginate, galactan, laminaran, and naviculan) with different antiviral activities and mechanisms of action have been recently reported (Ahmadi et al. 2015; Zubia et al. 2008).

3 Induction of Lipids, Peptides, and Carbohydrates of Commercial Value

Algae differ in their tolerance and adaptability to the environmental conditions. Under stress conditions, algae accumulate elevated amounts of some metabolites for protection and recovery from injury. The growth of Botryococcus braunii (race ‘A’) and production of its constituents, hydrocarbon, carbohydrate, fatty acid, and carotenoids were influenced by different levels of salinity (Ranga Rao et al. 2007a, b). Different microalgae species react to different stresses by producing different fatty acids or by altering their composition of fatty acids. The exact combination of induction stresses that provides optimum lipid productivity in a large-scale commercial cultivation system for biodiesel production will differ for every microalgae strain and depends on nutrient supply, environmental and climatic conditions (Mata et al. 2010; Sharma et al. 2012). Several studies have focused on the increase of lipid productivity by the cultivation of microalgae with different levels of CO2, (Yoo et al. 2010; Ranga Rao et al. 2007a, b), nitrogen concentration and temperature, to mitigate CO2 due to its C-fixation ability and for production of biodiesel. In algae and cyanobacteria, several protection mechanisms against ultraviolet stress have been reported (Xue 2005; Lee et al. 2014; Hartmann et al. 2015). Spirulina platensis produced relevant amounts of sulfated polysaccharides as adaptation mechanisms to nitrogen concentration (Abd El Baky et al. 2013).

4 Several Secondary Metabolites

Secondary metabolites have gained great attention over the last 50 years because they showed a wide variety of pharmacological uses. These molecules are mainly involved in the adaptation of organisms to their environment (Bourgaud et al. 2001).

The metabolism is the sum of all the biochemical processes that take place in an organism. Secondary metabolic pathways produce a huge number of compounds: alkaloids, carotenoids, phenolic compounds, lignin, phytosterols, and others (Hussain et al. 2012). The major metabolic reactions that occur in algae are unique and produce unique secondary metabolites: mechanisms of light harvesting, carbon acquisition and aspects of nitrogen (N) and sulfur (S) assimilation, growth in extreme environments, such as nutrient limitation and exposure to extremes of visible and UV light (Beardal and Ravenm 2012). It has been reported that algal species cultivated under stress conditions produce relevant amounts of metabolites for pharmaceutical uses (Leu and Boussiba 2014; Yu et al. 2015).

Carotenoids

Microalgae are rich in carotenoids, being especially high in Dunaliella species where it is up to 14% of dry weight (Spolaore et al. 2006). They are over 400 known carotenoids but only one small fraction is commercially produced, highlighting β-carotene, astaxanthin, lutein, zeaxanthin, lycopene, and bixin (Radmer 1996; del Campo et al. 2000). The green flagellate microalgae Dunaliella salina is the most important species in the production of β-carotene (Metting 1996). In general, these carotenoids are a strong antioxidant, making them highly relevant in terms of industrial production.

Algal carotenoids are involved in different functions: in photosynthesis, as intermediates of carotenogenesis or as accumulated carotenoids (Takaichi 2011). They have been found to protect against several malfunctions and diseases triggered by oxidative stress (Abd El Baky 2003; Fassett and Coombes 2011).

Fucoxanthin is a marine carotenoid widely distributed in microalgae and brown macroalgae, involved in a multitude of molecular and cellular processes, showing a protective role and anti-proliferative behavior in several types of cancer (Kotake-Nara 2005; Mikami and Hosokawa 2013; Satomi 2012). In fact, the regular consumption of seaweeds containing high quantities of fucoxanthin is believed to be the reason for the longevity of certain populations (Kumar et al. 2013).

Astaxanthin, a rare ketocarotenoid synthesized only by limited numbers of organisms, has therapeutic applications, for example, against free radical-associated diseases like oral, colon, and liver cancers, cardiovascular diseases, and degenerative eye diseases (Han et al. 2013). Several reviews focused on carotenoids from algae have recently been published (Jin and Melis 2003; Guedes et al. 2011; Mezzomo and Ferreira 2016; Takaichi 2011). Moreover, astaxanthin is a main compound in the salmon feed industry with more than US$200 million (Hejazi and Wijffels 2004).

Phycobiliproteins

The most common phycobiliproteins in the industry are phycoerythrin and phycocyanin that can be produced by Arthrospira species and Porphyridium species (Viskari and Colyer 2003; Roman et al. 2002). The application of phycobiliproteins is focused in health-promoting properties, such as food pigment. On the other hand, phycobiliproteins are interesting in clinical applications due to their high molar absorbance coefficients, high fluorescence quantum yield, and high photostability. In this sense, phycobiliproteins can be used as labels in fluorescence medical diagnostics (Roman et al. 2002).

Phytosterols

Recently has been published a review focused on microalgae-derived phytosterols applications in functional food and pharmaceutical industries (Luo et al. 2015). Phytosterols are important structural components of the cellular membrane and have important functions in regulating membrane fluidity and permeability. They also exist as hormones or hormonal precursors and are involved in signal transduction in the organisms. In addition, phytosterols reduce the level of cholesterol in blood helping to prevent cardiovascular disorders (Ras et al. 2013; Gylling et al. 2014).

Phenolic Compounds

Waterman and Mole (1994) defined polyphenolic secondary metabolites as a large and diverse group of chemical compounds, which are common both in terrestrial plants and in aquatic macrophytes (without citing microalgae). The term phenolic includes more than 8000 naturally compounds with one common structural feature, a phenol. The phenolic compounds are divided into two groups according to the number of phenol subunits: simple phenols and polyphenols (with at least two phenol subunits) (Leopoldini et al. 2011), and tannins were described as compounds possessing three or more phenol subunits (Clifford 1999). Polyphenols are primarily recognized for their antioxidant capability toward free radicals normally produced by cells metabolism or in response to external factors. In living systems under stress, the excessive generation of hydroxyl radical (OH) and other highly reactive oxygen species (ROS) produce oxidative damage through the reaction of these species with almost every cellular biomolecules including DNA. Many studies on pharmacological research have evidenced that oxidative stress and increased amounts of free radicals are features of chronic diseases including cancer (Klaunig and Kamendulis 2004), aging and neurodegenerative diseases such as Alzheimer’s and Parkinson’s (Nunomura et al. 2006; Wood-Kaczmar et al. 2006) and cardiovascular diseases such as atherosclerosis (Siti et al. 2015). They are the primary causes of cell death and tissue damage resulting from a heart attack and stroke (Perron and Brumaghim 2009). Phenolic compounds are radical scavengers and inhibit metal-mediated oxyradical formation preventing various processes of oxidative stress considered the origin of the above-cited diseases (Jomova and Valkoa 2011; Zhaoa et al. 2005; Aprioku 2013). Therefore, polyphenols display a number of pharmacological, medicinal and biochemical properties extensively reviewed: they present antiviral, anti-inflammatory, antibacterial, and antihistamine activities, cardiovascular effects and are implicated in the prevention of neurodegenerative diseases (Brit et al. 2001; Dai and Mumper 2010; Graf et al. 2005; Hertog et al. 1993; Mandel et al. 2006; Lambert and Yang 2003; Pandey and Rizvi 2009; Quideau et al. 2011).

Several mechanisms have been proposed for polyphenol prevention of oxidative stress: they are able to inhibit free radicals according to the hydrogen atom transfer and to the single electron transfer mechanisms. In the first one, the bond dissociation enthalpy of the phenolic O–H bond is an important parameter in evaluating the antioxidant action, while in the second the ionization potential is the most significant parameter for the scavenging activity evaluation. These mechanisms often take place simultaneously and depend on the pH (Leopoldini 2011; Perron and Brumaghim 2009). Polyphenols are also capable of chelating metal ions leading to stable complex compounds and avoiding them to take part in the reactions generating free radicals (Flora 2009).

Among phenolic compounds, phlorotannins (polymers of phloroglucinol units linked to each other in various ways) have only been detected in brown algae (Koivikko et al. 2007; Li et al. 2011; Ragan and Glombitza 1986) such as seaweeds Ecklonia sp., which have provided various phlorotannins with diverse biological activities (Kang et al. 2004; Kim et al. 2006: Shin et al. 2014; Wijesinghe et al. 2011). Consumption of phlorotannin-rich algae Fucus distichus and Ecklonia cava may be useful for the treatment of diabetes (Kellogg et al. 2014; Lee and Jeon 2015). Phlorotannin dieckol, isolated from the edible brown algae Ecklonia cava, suppresses ovarian cancer cell growth (Ahn et al. 2015) and shows antithrombotic activity among others, useful in the development of agents for the anticoagulation (Kim et al. 2012).

On the other hand, only a few references have dealt with the beneficial effects of phenolic compounds from microalgae in human health. Despite marine microalgae are known to produce numerous useful products, have attracted little attention in the search of polyphenolic compounds. Recently, several methodologies for identification and quantification of polyphenolic compounds from microalgae extracts have been reported (Rico et al. 2013; López et al. 2015). These publications are focused on the implications of polyphenols in microalgae growing under metal stress paying special attention to the influence of Cu(II) and Fe(III) metals on the cells and exudated phenolic profiles of the marine green microalgae Dunaliella tertiolecta and the marine diatoms Phaeodactylum tricornutum. In these studies, the authors measured the concentration of gallic acid, protocatechuic acid, (+) catechin, vanilic acid, (−) epicatechin, syringic acid, gentisic acid, caffeic acid, coumaric acid, ferulic acid, rutin, myricetin and quercetin.

Significant differences in the phenolic profiles were found depending on the metal added to the seawater indicating the involvement of polyphenols in the microalgae cellular response under a high level of Cu(II) and Fe(III) in natural seawater. The presence of these polyphenols was also measured in the control experiments (without stress conditions) and their concentrations, both in solution and in cells, were affected by the stress caused by the addition of metals. The great increase in phenolic compounds exuded by the cells at the highest copper concentration may reflect the involvement of these compounds in protection in conditions of copper toxicity (Fig. 3).
Fig. 3

Phenolic compounds exuded by Phaeodactylum tricornutum and Dunaliella tertiolecta cultured in seawater, during 8 days without metals (control) and after Cu(II) additions. Data collected from Rico et al. (2013) and Lopez et al. (2015)

Cells exposed to copper excreted a larger amount of polyphenols as a protective mechanism to alleviate the toxicity of the copper in the solution: these phenolic compounds are implicated countering metal toxicity at the membrane surface and slowing down the toxicity of metals in the extracellular media.

Iron is an essential mineral for all forms of life. Excess of iron results in cellular damage due to the proclivity of this transition metal to generate reactive oxygen species through Fenton chemistry, being necessary a stringent control of iron atoms once they are inside the cell (Foley and Simeonov 2012). In fact, diatom Phaeodactylum tricornutum exposed to high levels of iron produced relevant amounts of phenolic compounds in the cells (Rico et al. 2013). By other hand, microorganisms have developed pathways to synthesize, secrete, and retrieve small molecule chelators that display an unprecedented affinity for ferric and ferrous ions (Foley and Simeonov 2012). The concentration of phenolic compounds exuded by diatom Phaeodactylum tricornutum cultivated in seawater enriched with iron increased from 24 nmol L−1 (control) to 28 nmol L−1 because polyphenols are potent metal ion chelators (Wang et al. 2009). In addition, phenolic compounds exuded from microalgae, such as sinapic acid and (+) catechin, have shown also an influence in iron redox chemistry by favoring the persistence of Fe(II) for the requirements of the cells (Santana-Casiano et al. 2014). These compounds favored reduction of Fe (III) to Fe (II), which is a pH-dependent process, being the percentage of Fe (II) regenerated always higher in the presence of (−) catechin than in the presence of sinapic acid (Fig. 4).
Fig. 4

Percentage of regenerated Fe (II) from initial concentration of 200 nM Fe(III) at pH = 6.00 in seawater and in 0.7 M NaCl (+2 mM NaHCO3). Data from Santana-Casiano et al. (2014)

The extracts of Dunaliella tertiolecta and Phaeodactylum tricornutum showed antioxidant activity and high amounts of phenolics confirming their pharmaceutical and medicinal value.

Notes

Acknowledgements

Authors thank the Project CTM2014-52342-P given by the Ministerio de Economia y Competitividad from Spain. Aridane G. Gonzalez thanks the French “Agence Nationale de la Recherche” through the “Laboratoire d’Excellence” LabexMER (ANR-10-LABX-19-01) program, and co-funded by a grant from the French government through the “Investissements d’Avenir” and the Brittany Region.

References

  1. Abd El Baky HH, El Baz FK, El-Barouty GS (2003) Spirulina species as a source of carotenoids and α-tocopherol and its anticarcinoma factors. Biotechnol 3:222–240Google Scholar
  2. Abd El Baky HH, Hanaa El Baz KF, EL-Latife SA (2013) Induction of sulfated polysaccharides in Spirulina platensis as response to nitrogen concentration and its biological evaluation. J Aquac Res Development 5:206, 8 pagesGoogle Scholar
  3. Abd El Baky HH, El-Baroty GS, Ibrahim AE, El Baz FK (2014) Cytotoxicity, antioxidants and antimicrobial activities of lipids extracted from some marine algae. J Aquac Res Dev 5:284, 5 pagesGoogle Scholar
  4. Abd El Baky HH, El Baz FK, El Baroty GS, Asker MMS, Ibrahim EA (2014b) Phospholipids of some marine macroalgae: identification, antivirus, anticancer and antimicrobial bioactivities. Der Pharma Chemica 6:370–382Google Scholar
  5. Abreu MH, Pereira R, Sassi JF (2014) Marine algae and the global food industry. In: Pereira L, Neto JM (eds) Marine algae: biodiversity, taxonomy. Environmental assessment and biotechnology. CRC Press, pp 300–319Google Scholar
  6. Ahn JH, Yang YI, Lee KT, Choi JH (2015) Dieckol, isolated from the edible brown algae Ecklonia cava, induces apoptosis of ovarian cancer cells and inhibits tumor xenograft growth. J Cancer Res Clin Oncol 141:255–268CrossRefPubMedGoogle Scholar
  7. Ahmadi A, Moghadamtousi SZ, Abubakar S, Zandi K (2015) Antiviral potential of algae polysaccharides isolated from marine sources: a review. In: BioMed research international. Article ID 825203, 10 pagesGoogle Scholar
  8. Andersen G, Harnack K, Erbersdobler HF, Somoza V (2008) Dietary eicosapentaenoic acid and docosahexaenoic acid are more effective than alpha-linolenic acid in improving insulin sensitivity in rats. Ann Nutr Metab 52:250–256CrossRefPubMedGoogle Scholar
  9. Aprioku JS (2013) Pharmacology of free radicals and the impact of reactive oxygen species on the testis. J Reprod Infertil 14:158–172PubMedPubMedCentralGoogle Scholar
  10. Barahona T, Encinas MV, Imarai M, Mansilla A, Matsuhiro B, Torres R, Valenzuela B (2014) Bioactive polysaccharides from marine algae. Bioactive Carbohydr Diet Fibre 4:125–138CrossRefGoogle Scholar
  11. Beardal J, Raven, JA (2012) Algal metabolism. In: eLS Chichester. WileyGoogle Scholar
  12. Becker W (2004) 18 Microalgae in human and animal nutrition. Handbook of microalgal culture: biotechnology and applied phycology, p 312Google Scholar
  13. Becker EW (2007) Micro-algae as a source of protein. Biotech Adv 25(2):207–210Google Scholar
  14. Boopathy NS, Kathiresan K (2010) Anticancer drugs from marine flora: an overview. J Oncol Article ID 214186, 18 pagesGoogle Scholar
  15. Borowitzka MA (1995) Microalgae as sources of pharmaceuticals and other biologically active compounds. J Appl Phycol 7:3–15CrossRefGoogle Scholar
  16. Borowitzka MA (2013) High-value products from microalgae—their development and commercialisation. J Appl Phycol 25:743–756CrossRefGoogle Scholar
  17. Bourgaud F, Gravot A, Milesi S, Gontier E (2001) Production of plant secondary metabolites: a historical perspective. Plant Sci 161:839–851CrossRefGoogle Scholar
  18. Brit DF, Hendrich S, Wang W (2001) Dietary agents in cancer prevention: flavonoids and isoflavonoids. Pharmacol Ther 90:157–177CrossRefGoogle Scholar
  19. Castro LFC, Tocher DR, Monroig O (2016) Long-chain polyunsaturated fatty acid biosynthesis in chordates: insights into the evolution of Fads and Elovl gene repertoire. Prog Lipid Res 62:25–40CrossRefPubMedGoogle Scholar
  20. Chu WL, Phang SM, Goh SH (1994) Studies on the production of useful chemicals, especially fatty acids in the marine diatom Nitzschia conspicua Grunow. In: Ecology and conservation of southeast Asian marine and freshwater environments including wetlands. Springer, Netherlands, pp 3–40Google Scholar
  21. Clifford MN Appendix 1. A nomenclature for phenols with special reference to tea. Washington, DC, 11/1999, CRC Press LLC: Boca Raton, Florida, vol 41, Supplement 5, pp 393–397Google Scholar
  22. Cornish ML, Garbary DJ (2010) Antioxidants from macroalgae: potential applications in human health and nutrition. Algae 25:155–171CrossRefGoogle Scholar
  23. Dai J, Mumper RJ (2010) Plant phenolics: extraction, analysis and their antioxidant and anticancer properties. Molecules 15:7313–7352CrossRefPubMedGoogle Scholar
  24. Damonte E, Neyts J, Pujol CA, Snoeck R, Andrei G, Ikeda S, Witvrouw M, Reymen D, Haines H, Matulewicz MC, Cerezo A, Coto CE, de Clercq E (1994) Antiviral activity of a sulphated polysaccharide from the red seaweed Nothogenia fastigiata. Biochem Pharmacol 47:2187–2192CrossRefPubMedGoogle Scholar
  25. De Clercq E (1996) Chemotherapy of human immunodeficiency virus (HIV) infection: anti-HIV agents targeted at early stages in the virus replicative cycle. Biomed Pharmacother 50:207–215CrossRefPubMedGoogle Scholar
  26. Del Campo JA, Moreno J, Rodrı́guez H, Vargas MA, Rivas J, Guerrero MG (2000) Carotenoid content of chlorophycean microalgae: factors determining lutein accumulation in Muriellopsis sp. (Chlorophyta). J Biotech 76:51–59Google Scholar
  27. Ehresmann DW, Deig EF, Hatch MT (1979) Antiviral properties of algal polysaccharides and related compounds. In: Hoppe HA et al (eds) Marine algae in pharmaceutical science. W de Gruyter, NY, pp 293–302Google Scholar
  28. El Baz FK, Aboul-Enein AM, El-Baroty GS, Youssef AM, Abdel-Baky HH (2002) Accumulation of antioxidant vitamins in Dunaliella salina. J Biol Sci 2:220–223CrossRefGoogle Scholar
  29. Fan X, Bai L, Zhu L, Yang L, Zhang X (2014) Marine algae-derived bioactive peptides for human nutrition and health. J Agric Food Chem 62:9211–9222CrossRefPubMedGoogle Scholar
  30. Farvin KHS, Jacobsen C (2013) Phenolic compounds and antioxidant activities of selected species of seaweeds from Danish coast. Food Chem 138:1670–1681CrossRefGoogle Scholar
  31. Fassett RG, Coombes JS (2011) Astaxanthin: a potential therapeutic agent in cardiovascular disease. Mar Drugs 9:447–465CrossRefPubMedPubMedCentralGoogle Scholar
  32. Flora SJ (2009) Structural, chemical and biological aspects of antioxidants for strategies against metal and metalloid exposure. Oxid Med Cell Longev 2:191–206CrossRefPubMedPubMedCentralGoogle Scholar
  33. Foley TL, Simeonov A (2012) Targeting iron assimilation to develop new antibacterials. Expert Opin Drug Discov 7:831–847CrossRefPubMedPubMedCentralGoogle Scholar
  34. Ghazala B, Nailaand B, Shameel M (2010) Fatty acids and biological activities of crude extracts of freshwater algae from sindh. Pak J Bot 42:1201–1212Google Scholar
  35. Graf BA, Milbury PE, Blumberg JB (2005) Flavonols, flavonones, flavanones and human health: epidemological evidence. J Med Food 8:281–290CrossRefPubMedGoogle Scholar
  36. Guedes AC, Amaro HM, Malcata FX (2011) Microalgae as sources of carotenoids. Mar Drugs 9:625–644CrossRefPubMedPubMedCentralGoogle Scholar
  37. Grima EM, Belarbi EH, Fernández FA, Medina AR, Chisti Y (2003) Recovery of microalgal biomass and metabolites: process options and economics. Biotech Adv 20:491–515CrossRefGoogle Scholar
  38. Gupta S, Abu-Ghannam N (2011) Bioactive potential and possible health effects of edible brown seaweeds. Trends Food Sci Technol 22:315–326CrossRefGoogle Scholar
  39. Gylling H, Plat J, Turley S, Ginsberg HN, Ellegård L, Jessup W, Jones PJ, Lütjohann D, Maerz W, Masana L, Silbernagel G, Staels B, Borén J, Catapano AL, De Backer G, Deanfield J, Descamps OS, Kovanen PT, Riccardi G, Tokgözoglu L, Chapman MJ (2014) Plant sterols and plant stanols in the management of dyslipidaemia and prevention of cardiovascular disease. Atherosclerosis 232:346–360CrossRefPubMedGoogle Scholar
  40. Han D, Li Y, Hu Q (2013) Astaxanthin in microalgae: pathways, functions and biotechnological implications. Algae 28:131–147CrossRefGoogle Scholar
  41. Hartmann A, Albert A, Ganzera M (2015) Effects of elevated ultraviolet radiation on primary metabolites in selected alpine algae and cyanobacteria. J Photochem Photobiol B 149:149–155CrossRefPubMedPubMedCentralGoogle Scholar
  42. Harwood JL, Guschina IA (2009) The versatility of algae and their lipid metabolism. Biochimie 91:679–684CrossRefPubMedGoogle Scholar
  43. Hejazi MA, Wijffels RH (2004) Milking of microalgae. Trends Biotechnol 22:189–194CrossRefPubMedGoogle Scholar
  44. Hertog MGL, Feskens EJM, Hollman PCH, Katan MB, Kromhout D (1993) Dietary antioxidant flavonoids and risk of coronary heart disease. Zutphen Elder Study Lancet 342:1007–1011Google Scholar
  45. Hossain Z, Kurihara H, Hosokavca M, Takahashp K (2005) Growth inhibition and induction of differentiation and apoptosis mediated by sodium butyrate in caco-2 cells with algal glycolipids. In Vitro Cell Dev Biol Animal 41:154–159CrossRefGoogle Scholar
  46. Hussain MdS, Fareed S, Ansari S, Rahman MdA, Ahmad IZ, Saeed M (2012) Current approaches toward production of secondary plant metabolites. J Pharm Bioallied Sci 4:10–20CrossRefPubMedPubMedCentralGoogle Scholar
  47. Jin ES, Melis A (2003) Microalgal biotechnology: carotenoid production by the green algae Dunaliella salina. Biotech Bioprocess Eng 8:331CrossRefGoogle Scholar
  48. Jomova K, Valkoa M (2011) Importance of iron chelation in free radical-induced oxidative stress and human disease. Curr Pharm Des 17:3460–3473CrossRefPubMedGoogle Scholar
  49. Kang HS, Chung HY, Kim JY, Son BW, Jung HA, Choi JS (2004) Inhibitory phlorotannins from the edible brown alga Ecklonia stolonifera on total reactive oxygen species (ROS) generation. Arch Pharm Res 27:194–198CrossRefPubMedGoogle Scholar
  50. Kang HK, Seo CH, Park Y (2015a) Marine peptides and their anti-infective activities. Mar Drugs 13:618–645CrossRefPubMedPubMedCentralGoogle Scholar
  51. Kang HK, Seo CH, Park Y (2015b) The effects of marine carbohydrates and glycosylated compounds on human health. Int J Mol Sci 16:6018–6056CrossRefPubMedPubMedCentralGoogle Scholar
  52. Kellogg J, Grace MH, Lila MA (2014) Phlorotannins from Alaskan seaweed inhibit carbolytic enzyme activity. Mar Drugs 12:5277–5294CrossRefPubMedPubMedCentralGoogle Scholar
  53. Kim MM, Ta QV, Mendis E, Rajapakse N, Jung WK, Byun HG, Jeon YJ, Kim SK (2006) Phlorotannins in Ecklonia cava extract inhibit matrix metalloproteinase activity. Life Sci 79:1436–1443Google Scholar
  54. Kim SK, Kang KH (2011) Medicinal effects of peptides from marine microalgae. Adv Food Nutr Res 64:313–323CrossRefPubMedGoogle Scholar
  55. Kim TH, Ku SK, Bae JS (2012) Antithrombotic and profibrinolytic activities of eckol and dieckol. J Cell Biochem 113:2877–2883CrossRefPubMedGoogle Scholar
  56. Kiriyama S, Okazaki Y, Yoshida A (1969) Hypocholesterolemic effect of polysaceharides and polysaccharide-rich foodstuffs in cholesterol-fed rats. J Nutr 97:382–388PubMedGoogle Scholar
  57. Klaunig JE, Kamendulis LM (2004) The role of oxidative stress in carcinogenesis. Annu Rev Pharmacol Toxicol 44:239–267CrossRefPubMedGoogle Scholar
  58. Koivikko R, Loponen J, Pihlaja K, Jormalainen V (2007) High-performance liquid chromatographic analysis of phlorotannins from the brown alga Fucus vesiculosus. Phytochem Anal 18:326–332CrossRefPubMedGoogle Scholar
  59. Kotake-Nara E, Terasaki M, Nagao A (2005) Characterization of apoptosis induced by fucoxanthin in human promyelocytic leukemia cells. Biosci Biotechnol Biochem 69:224–227CrossRefPubMedGoogle Scholar
  60. Kumar SR, Hosokawa M, Miyashita K (2013) Fucoxanthin: a marine carotenoid exerting anti-cancer effects by affecting multiple mechanisms. Mar Drugs 11:5130–5147CrossRefPubMedPubMedCentralGoogle Scholar
  61. Kumari P, Kumar M, Reddy CRK, Jha, B (2013) Algal lipids, fatty acids and sterols. In Dominguez H (ed) Functional ingredients from algae for foods and nutraceuticals. Woodhead Publishing, pp 87–134Google Scholar
  62. Lambert JD, Yang CS (2003) Mechanisms of cancer prevention by tea constituents. J Nutr 133(Suppl):3262S–3267SPubMedGoogle Scholar
  63. Lamela M, Anca J, Villar R, Otero J, Calleja JM (1989) Hypoglycemic activity op several seaweed extracts. J Ethnopharmacol 27:35–43CrossRefPubMedGoogle Scholar
  64. Lee SH, Jeon YJ (2015) Efficacy and safety of a dieckol-rich extract (AG-dieckol) of brown algae, ecklonia cava, in pre-diabetic individuals: a double-blind, randomized, placebo-controlled clinical trial. Food Funct 6:853–858CrossRefPubMedGoogle Scholar
  65. Lee TK, Kottuparambil S, Kim YJ, Rhee JS, Choi EM, Brown MT, Häder DP, Taejun H (2014) Ultraviolet radiation and cyanobacteria. J Photochem Photobiol B 141:154–169CrossRefPubMedGoogle Scholar
  66. Leopoldini M, Russo N, Toscano M (2011) The molecular basis of working mechanism of natural polyphenolic antioxidants. Food Chem 125:288–306CrossRefGoogle Scholar
  67. Leu S, Boussiba S (2014) Advances in the production of high-value products by microalgae. Ind Biotechnol 10:169–183CrossRefGoogle Scholar
  68. Li Y-X, Wijesekara I, Li Y, Kim S-K (2011) Phlorotannins as bioactive agents from brown algae. Process Biochem 46:2219–2224CrossRefGoogle Scholar
  69. Li A-N, Li S, Zhang Y-J, Xu X-R, Chen Y-M, Li H-B (2014) Resources and biological activities of natural polyphenols. Nutrients 6:6020–6047CrossRefPubMedPubMedCentralGoogle Scholar
  70. López A, Rico M, Santana-Casiano JM, Gonzaléz AG, González-Dávila M (2015) Phenolic profile of Dunaliella tertiolecta growing under high levels of copper and iron. Environ Sci Pollut Res 22:14820–14828CrossRefGoogle Scholar
  71. Luo X, Su P, Zhang W (2015) Advances in microalgae-derived phytosterols for functional food and pharmaceutical applications. Mar Drugs 13:4231–4254CrossRefPubMedPubMedCentralGoogle Scholar
  72. Machu L, Misurcova L, Ambrozova JV, Orsavova J, Mlcek J, Sochor J, Jurikova T (2015) Phenolic content and antioxidant capacity in algal food products. Molecules 20:1118–1133CrossRefPubMedGoogle Scholar
  73. Mandel SA, Amit T, Zheng H, Weinreb O, Youdim MBH (2006) The essentiality of iron chelation in neuroprotection: a potential role of green tea catechins. In: Luo Y, Packer L (eds) Oxidative stress and disease. CRC Press, pp 277–299Google Scholar
  74. Mata TM, Antonio A, Martins N, Caetano S (2010) Microalgae for biodiesel production and other applications: a review. Renew Sustain Energy Rev 14:217–232CrossRefGoogle Scholar
  75. Metting FB Jr (1996) Biodiversity and application of microalgae. J Ind Microbiol 17:477–289Google Scholar
  76. Mezzomo N, Ferreira SRS (2016) Carotenoids functionality, sources, and processing by supercritical technology: A review. J Chem vol. 2016, Article ID 3164312, 16 pagesGoogle Scholar
  77. Michalak I, Chojnacka K (2015) Algae as production systems of bioactive compounds. Eng Life Sci 15:160–176CrossRefGoogle Scholar
  78. Mikami K, Hosokawa M (2013) Biosynthetic pathway and health benefits of fucoxanthin, an algae-specific xanthophyll in brown seaweeds. Int J Mol Sci 14:13763–13781CrossRefPubMedPubMedCentralGoogle Scholar
  79. Norton TA, Melkonian M, Andersen RA (1996) Algal biodiversity. Phycologia 35:308–326CrossRefGoogle Scholar
  80. Nunomura A, Castellani RJ, Zhu X, Moreira PI, Perry G, Smith MA (2006) Involvement of oxidative stress in Alzheimer disease. J Neuropathol Exp Neurol 65:631–641CrossRefPubMedGoogle Scholar
  81. Panlasigui LN PhD, Baello OQ, Dimatangal JM BSc, Dumelod BD MSc (2003) Blood cholesterol and lipid-lowering effects of carrageenan on human volunteers. Asia Pacific J Clin Nut 12:209–214Google Scholar
  82. Pandey KB, Rizvi SI (2009) Plant polyphenols as dietary antioxidants in human health and disease. Oxid Med Cell Longev 2:270–278CrossRefPubMedPubMedCentralGoogle Scholar
  83. Pangestuti R, Kim SK (2011) Biological activities and health benefit effects of natural pigments derived from marine algae. J Funct Foods 3:255–266CrossRefGoogle Scholar
  84. Perron NR, Brumaghim JL (2009) A review of the antioxidant mechanisms of polyphenol compounds related to iron binding. Cell Biochem Biophys 53:75–100CrossRefPubMedGoogle Scholar
  85. Pratt R, Fong J (1940) Studies on Chlorella vulgaris II. Further evidence that Chlorella cells form a growth-inhibiting substance. Am J Bot 27:431–436CrossRefGoogle Scholar
  86. Priyadarshani I, Rath B (2012) Commercial and industrial applications of micro algae—a review. J Algal Biomass Utilization 3:89–100Google Scholar
  87. Quideau S, Deffieux D, Douat-Casassus C, Pouységu L (2011) Plant polyphenols: chemical properties, biological activities, and synthesis. Angew Chem 50:586–621CrossRefGoogle Scholar
  88. Radmer RJ (1996) Algal diversity and commercial algal products. Bioscience 46:263–270CrossRefGoogle Scholar
  89. Ragan MA, Glombitza KW (1986) Phlorotannins, brown algal polyphenols. Prog Phycol Res 4:129–241Google Scholar
  90. Ranga Rao A, Dayananda C, Sarada R, Shamala TR, Ravishankar GA (2007a) Effect of salinity on growth of green alga Botryococcus braunii and its constituents. Bioresour Technol 98:560–564CrossRefPubMedGoogle Scholar
  91. Ranga Rao A, Sarada TR, Ravishankar GA (2007b) Influence of CO2 on growth and hydrocarbon production in Botryococcus braunii. J Microbiol Biotechnol 17:414–419PubMedGoogle Scholar
  92. Ras RT, Hiemstra H, Lin Y, Vermeer MA, Duchateau GSMJE, Trautwein EA (2013) Consumption of plant sterol-enriched foods and effects on plasma plant sterol concentrations—a meta-analysis of randomized controlled studies. Atherosclerosis 230:336–346CrossRefPubMedGoogle Scholar
  93. Rico M, López A, Santana-Casiano JM, González AG, González-Dávila M (2013) Variability of the phenolic profile in the diatom Phaeodactylum tricornutum growing under copper and iron stress. Limnol Oceanogr 58:144–152CrossRefGoogle Scholar
  94. Román RB, Alvarez-Pez JM, Fernández FA, Grima EM (2002) Recovery of pure B-phycoerythrin from the microalga Porphyridium cruentum. J Biotechnol 93:73–85CrossRefGoogle Scholar
  95. Santana-Casiano JM, González-Dávila M, González AG, Rico M, López A, Martel A (2014) Characterization of polyphenol exudates from Phaeodactylum tricornutum and their effects on the chemistry of Fe(II)-Fe(III). Mar Chem 158:10–16CrossRefGoogle Scholar
  96. Satomi Y (2012) Fucoxanthin induces GADD45A expression and G1 arrest with SAPK/JNK activation in LNCap human prostate cancer cells. Anticancer Res 32:807–813PubMedGoogle Scholar
  97. Scala S, Bowler C (2001) Molecular insights into the novel aspects of diatom biology. Cell Mol Life Sci 58:1666–1673CrossRefPubMedGoogle Scholar
  98. Shalaby EA (2011) Algae as promising organisms for environment and health. Plant Signal Behav 6:1338–1350CrossRefPubMedPubMedCentralGoogle Scholar
  99. Sharma KK, Schuhmann H, Schenk PM (2012) High lipid induction in microalgae for biodiesel poduction. Energies 5:1532–1553CrossRefGoogle Scholar
  100. Shimizu Y (1996) Microalgal metabolites: a new perspective. Ann Rev Microbiol 50:431–465CrossRefGoogle Scholar
  101. Shimizu Y (2000) In: Fusetani N (ed) Drugs from the sea. Karger, Basel, pp 30–45CrossRefGoogle Scholar
  102. Shin T, Ahn M, Hyun JW, Kim SH, Moon C (2014) Antioxidant marine algae phlorotannins and radioprotection: a review of experimental evidence. Acta Histochem 116:669–674CrossRefPubMedGoogle Scholar
  103. Siti HN, Kamisah Y, Kamsiah J (2015) The role of oxidative stress, antioxidants and vascular inflammation in cardiovascular disease (a review). Vascul Pharmacol 71:40–56CrossRefPubMedGoogle Scholar
  104. Spolaore P, Joannis-Cassan C, Duran E, Isambert A (2006) Commercial applications of microalgae. J Biosci Bioeng 101:87–96CrossRefPubMedGoogle Scholar
  105. Takaichi S (2011) Carotenoids in algae: distributions, biosyntheses and functions. Mar Drugs 9:1101–1118CrossRefPubMedPubMedCentralGoogle Scholar
  106. Yoo C, Jun SY, Lee JY, Ahn CY, Oh HM (2010) Selection of microalgae for lipid production under high levels carbon dioxide. Bioresource Technol 101:S71–S74CrossRefGoogle Scholar
  107. Viskari PJ, Colyer CL (2003) Rapid extraction of phycobiliproteins from cultured cyanobacteria samples. Anal Biochem 319:263–271CrossRefPubMedGoogle Scholar
  108. Wang T, Jónsdóttir R, Ólafsdóttir G (2009) Total phenolic compounds, radical scavenging and metal chelation of extracts from icelandic seaweeds. Food Chem 116:240–248CrossRefGoogle Scholar
  109. Waterman PG, Mole S (1994) Analysis of phenolic plant metabolites. Blackwell Scientific Publications, Oxford, Great BritainGoogle Scholar
  110. Wen W, Li K, Alseekh S, Omranian N, Zhao L, Zhou Y, Xiao Y, Jin M, Yang N, Liu H, Florian A, Li W, Pan Q, Nikoloski Z, Yan J, Fernie AR (2015) Genetic determinants of the network of primary metabolism and their relationships to plant performance in a maize recombinant inbred line population. Plant Cell 27:1839–1856CrossRefPubMedPubMedCentralGoogle Scholar
  111. Wijesinghe WAJP, Ko S-C, Jeon Y-J (2011) Effect of phlorotannins isolated from Ecklonia cava on angiotensin I-converting enzyme (ACE) inhibitory activity. Nutr Res Practice 5:93–100CrossRefGoogle Scholar
  112. Witvrouw M, Este JA, Mateu MQ, Reymen D, Andrei G, Snoeck R, Ikeda S, Pauwels R, Bianchini NV, Desmyter J, de Clercq E (1994) Activity of a sulfated polysaccharide extracted from the red seaweed Aghardhiella tenera against human immunodeficiency virus and other enveloped viruses. Antiviral Chem Chemother 5:297–303CrossRefGoogle Scholar
  113. Wood-Kaczmar A, Gandhi S, Wood NW (2006) Understanding the molecular causes of Parkinson’s disease. Trends Mol Med 12:521–528CrossRefPubMedGoogle Scholar
  114. Xue L, Zhang Y, Zhang T, An L, Wang X (2005) Effects of enhanced ultraviolet-B radiation on algae and cyanobacteria. Crit Rev Microbiol 31:79–89CrossRefPubMedGoogle Scholar
  115. Yu X, Chen L, Zhang W (2015) Chemicals to enhance microalgal growth and accumulation of high-value bioproducts. Front Microbiol 6:56, 10 pagesGoogle Scholar
  116. Zhaoa C, Dodina G, Yuanc C, Chena H, Zheng R, Jiac Z, Fana B-T (2005) In vitro protection of DNA from Fenton reaction by plant polyphenol verbascoside. Biochim Biophys Acta 1723:114–123CrossRefGoogle Scholar
  117. Zubia M, Payri C, Deslandes E (2008) Alginate, mannitol, phenolic compounds and biological activities of two range-extending brown algae, Sargassum mangarevense and Turbinaria ornata (Phaeophyta: Fucales), from Tahiti (French Polynesia). J Appl Phycol 20:1033–1043CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2017

Authors and Affiliations

  • Milagros Rico
    • 1
  • Aridane G. González
    • 1
  • Magdalena Santana-Casiano
    • 1
  • Melchor González-Dávila
    • 1
  • Norma Pérez-Almeida
    • 1
  • Miguel Suarez de Tangil
    • 1
  1. 1.Grupo QUIMA, Instituto de Oceanografía y Cambio Global (IOCAG)Universidad de Las Palmas de Gran CanariaLas Palmas de Gran CanariaSpain

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