Microalgae are microorganisms that have different morphological, physiological, and genetic traits that confer the ability to produce different biologically active metabolites. Microalgal biotechnology has become a subject of study for various fields, due to the varied bioproducts that can be obtained from these microorganisms. When microalgal cultivation processes are better understood, microalgae can become an environmentally friendly and economically viable source of compounds of interest, because production can be optimized in a controlled culture. The bioactive compounds derived from microalgae have anti-inflammatory, antimicrobial, and antioxidant activities, among others. Furthermore, these microorganisms have the ability to promote health and reduce the risk of the development of degenerative diseases. In this context, the aim of this review is to discuss bioactive metabolites produced by microalgae for possible applications in the life sciences.
Microalgae are unicellular microorganisms that grow in fresh or salt water and have varied shapes with a diameter or length of approximately 3–10
Microalgae are photosynthetic organisms that play a key role in aquatic ecosystems. Approximately 40% of global photosynthesis is due to these microorganisms [
Several studies have been conducted to investigate the products of microalgal metabolism not only to understand its nature but also to search for substances with possible applications to humans in different fields of interest. Screening of extracts or isolation of metabolites from different microalgae is a common method for determining the biological activity of these components. Microalgae have been described as rich sources of various biocompounds of commercial interest [
Bioactive compounds of microalgal origin can be sourced directly from primary metabolism, such as proteins, fatty acids, vitamins, and pigments, or can be synthesized from secondary metabolism. Such compounds can present antifungal, antiviral, antialgal, antienzymatic, or antibiotic actions [
Bioactive metabolites of microalgal origin are of special interest in the development of new products for medical, pharmaceutical, cosmetic, and food industries. Further research should be conducted with these bioactive compounds to verify their beneficial effects for humans, their degradability when released into the environment, and their effects when used in animals [
Microalgae are a group of heterogeneous microorganisms that have a great biodiversity of colors, shapes, and cell characteristics, and their manipulation is encompassed by the field of marine biotechnology. Among the thousands of species of microalgae believed to exist, only a small number of them are retained in collections around the world, and it is estimated that only a few hundreds are investigated for compounds present in their biomass. Of these, only and a few are industrially cultivated [
Microalgae are a natural source of highly interesting biologically active compounds. These compounds have received much attention from researchers and companies in recent years due to their potential applications in different life science fields. The applications range from the production of biomass for food and feed to the production of bioactive compounds for the medical and pharmaceutical industries [
Microalgae are autotrophic microorganisms that use light energy and inorganic nutrients (carbon dioxide, nitrogen, phosphorus, etc.) to develop and synthesize biocompounds that have high aggregated nutritional value and therapeutic functions, such as lipids, proteins, carbohydrates, pigments, and polymers. Recent studies have reported that microalgae can produce different chemical compounds with different biological activities, such as carotenoids, phycobilins, polyunsaturated fatty acids, proteins, polysaccharides, vitamins, and sterols among other chemicals [
Components of microalgal origin with antimicrobial, antiviral, anticoagulant antienzymatic, antioxidant, antifungal, anti-inflammatory, and anticancer activity, among others, were identified [
Principal bioactive compounds extracted from microalgae.
Microalgae | Bioactive compounds | Reference |
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Polysaccharides | [ |
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Phycocyanin, C-phycocyanin, Phenolic acids, tocopherols (vitamin E), neophytadiene, phytol, PUFAs ( |
[ |
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Diacylglycerols | [ |
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Astaxanthin, lutein, zeaxanthin, canthaxanthin, lutein, |
[ |
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Carotenoids, sulfated polysaccharides, sterols, PUFAs ( |
[ |
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Canthaxanthin, astaxanthin, peptide, oleic acid | [ |
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Eicosapentaenoic acid (EPA) | [ |
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Zeaxanthin, violaxanthin | [ |
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[ |
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Diacylglycerols | [ |
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Linear alkadienes (C25, C27, C29, and C31), triene (C29) | [ |
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Astaxanthin | [ |
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Lutein, zeaxanthin, canthaxanthin | [ |
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Lutein, sulfated polysaccharide | [ |
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Borophycin | [ |
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Cryptophycin | [ |
This microalga is rich in vitamins B1, B2, B12, and E (especially vitamin B12). Furthermore,
Bioactive compounds extracted from
Microalga | Bioactive compound | Concentration (%, w/w) | Reference |
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C-phycocyanin | 46.0 | [ |
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C-phycocyanin | 9.6 | [ |
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Allophycocyanin | 9.5 | [ |
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C-phycocyanin | 17.5 | [ |
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Allophycocyanin | 20.0 | [ |
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Phenolic | 0.71 | [ |
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Terpenoids | 0.14 | [ |
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Alkaloids | 3.02 | [ |
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Phenolic | 1.29 | [ |
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Flavonoids | 0.46 | [ |
Cyanobacteria are known to produce intracellular and extracellular metabolites with potential biological activities, such as antibacterial, antifungal, antiviral, antitumor, anti-HIV, anti-inflammatory, antioxidant, antimalarial, herbicidal, and immunosuppressant effects [
The world’s largest producer, Hainan Simai Pharmacy Co. (China), annually produces 3000 tonnes of
Microalga
Bioactive compounds extracted from the
Microalga | Bioactive compound | Concentration (%) | Reference |
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Phycocyanin | 20.0 (p/p) | [ |
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Phenolic | 0.61 (p/p) | [ |
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Terpenoids | 0.10 (p/p) | [ |
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Alkaloids | 2.30 (p/p) | [ |
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Phycobilins | 0.0229 (p/v) | [ |
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Phenolic | 0.34 (p/p) | [ |
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Terpenoids | 0.10 (p/p) | [ |
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Alkaloids | 1.65 (p/p) | [ |
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Phycobilins | 0.0031 (p/v) | [ |
Cyanovirin, a potential protein molecule produced by a
Microalga
This microalga was discovered by the Japanese, traditional consumers of algae, who usually enjoy it and use it as a food supplement. The microalga
These nutrient concentrations can be varied by manipulation of culture conditions. The biomass of this microalga is also rich in B complex vitamins, especially B12, which are vital in the formation and regeneration of blood cells. Like
Many antioxidant compounds may be responsible for
Bioactive compounds extracted from the microalgae of the
Microalga | Bioactive compound | Concentration (%, w/w) | Reference |
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Lutein | 4.60 | [ |
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Astaxanthin | 1.50 | [ |
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Phenolic | 0.20 | [ |
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Terpenoids | 0.09 | [ |
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Alkaloids | 2.45 | [ |
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Phytol | 2.70 | [ |
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Phenol | 1.81 | [ |
The most important bioactive compound in
This microalga is a major source of natural
Bioactive compounds extracted from the microalgae of the
Microalga | Bioactive compound | Concentration (%, w/w) | Reference |
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12% | [ | |
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All- |
13.8% | [ |
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All- |
1.1% | [ |
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All- |
0.66% | [ |
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Sterols | 1.3% | [ |
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Sterols | 0.89% | [ |
Compounds in the
Chang et al. [
Under ideal growing conditions,
The conditions for microalgal cultivation are important factors that influence the metabolism of these microorganisms, thus directing the synthesis of specific compounds of interest. Several researchers have noted the influence of incubation temperature, the pH of the medium, the period of cultivation, as well as salinity, light intensity, and medium constituents, on the synthesis of antimicrobial agents [
pH adjustments are the primary measures used to prevent contamination by microorganisms, such as other microalgae species. pH control is also essential for effective absorption of the components of the culture medium because it directly affects the availability of various chemical elements [
Light is an indispensable factor for photosynthesis, causing the cells to reproduce and thereby increasing the cell concentration [
One of the most important factors for the growth of all living organisms is the temperature. The specific growth rate of the microalgae is directly correlated with the gross rate of CO2 fixation/O2 production (photosynthesis) and the respiration rate. Photosynthesis and respiration are temperature-dependent, with the respiration rate increasing exponentially with temperature [
Microalgae have attracted much interest for production of bioactive compounds, and in order to grow and tap the potentials of algae, efficient photobioreactors are required. A good number of photobioreactors can be used in production of various algal products [
Bioreactors can be classified as open or closed. Closed photobioreactors have attracted much interest because they allow a better control of the cultivation conditions than open systems. One of the major advantages of open ponds is that they are easier to construct and operate than most closed systems [
In open systems, temperature is a main limiting factor, as are variations in solar radiation that lead to low biomass concentrations. However, open systems are the most widely used due to their economic viability. Closed systems are generally used on a pilot scale for investigating problems related to economic viability. Furthermore, the use of closed systems is primarily used for microalgal species that do not grow in a highly selective medium, avoiding contamination of the cultures [
Closed bioreactors can provide high productivity, generating greater microalgal biomass per unit time. Other advantages of the use of closed bioreactors compared with open systems include the following: (i) virtually zero losses in connection with evaporation; (ii) a marked reduction of problems related to culture contamination by heterotrophic algae or other microorganisms; (iii) ease of biomass collection procedures due to smaller volumes of culture medium; (iv) greater control of gas exchange between the culture and the atmosphere; (v) a smaller occupied space; (vi) a high surface:volume ratio, which helps to increase the illumination of the system; and (vii) the possibility of obtaining high purity cultures [
The metabolism of microalgae can be autotrophic or heterotrophic. The former requires only inorganic compounds, such as CO2, salts, and solar energy; the latter is not photosynthetic, requiring an external source of organic compounds for use as a nutrient and energy source. Some photosynthetic species are mixotrophic, having the ability to perform photosynthesis and use exogenous organic sources simultaneously [
Microalgae react to changes in their external environment with changes in their intracellular environment. Thus, the manipulation of the culture conditions or the presence or absence of nutrients stimulates the biosynthesis of specific compounds. This fact was first referenced by Richmond [
Noaman [
Culture media are chemical preparations that are formulated to contain the nutrients necessary for the microorganisms to multiply and/or survive. The culture media should meet the nutritional needs of the microorganism, assist in process control, and have a reasonably fixed composition [
Among different microalgae, variations in the culture medium are mainly related to the amount of necessary nutrients. Even so, nutritional needs are dependent on environmental conditions [
Microalgae are important sources of bioactive natural substances. Many metabolites isolated from these microorganisms have shown biological activities and potential health benefits [
Microalgae live in complex habitats and are subjected to stress and/or extreme conditions, such as changes in salinity, temperature, and nutrients. Thus, these microorganisms must rapidly adapt to new environmental conditions to survive and thus produce a great variety of biologically active secondary metabolites that are not found in other organisms [
In addition to their natural characteristics, other important aspects related to microalgae are the use of solar energy and carbon dioxide (CO2) and a high growth rate which can produce higher yields compared to higher plants. In addition, microalgae can be grown in areas and climates that are unsuitable for agriculture; therefore, microalgae do not compete with arable food production land. The possibility of controlling the production of certain bioactive compounds by manipulation of culture conditions is another advantage of using microalgae [
The cultivation of microalgae is a major mechanism for reducing excess carbon dioxide (CO2) in the atmosphere by biofixation, in which an industrial process uses a CO2-rich gas as a carbon source for microalgal growth. This mechanism contributes to a reduction of the greenhouse effect and global warming, further reducing the costs of the carbon source for growth, which is the greatest nutrient requirement for microalgae [
The cultivation of microalgae is not seasonal; they are important for food in aquaculture systems and can effectively remove pollutants, such as nitrogen and phosphorus, from wastewater. Moreover, they are the most efficient solar energy biomass converters. Microalgae cultivation via sunlight-dependent systems contributes to sustainable development and natural resource management [
The integration of the production process of bioactive metabolites in a biorefinery is a sustainable means of energy production, food production, and the production of products with high added value [
Bioactive compounds are physiologically active substances with functional properties in the human body. There is great enthusiasm for the development and manufacture of various biocompounds that can potentially be used as functional ingredients, such as carotenoids, phycocyanins, polyphenols, fatty acids, and polyunsaturated compounds [
An interest in the production of bioactive compounds from natural sources has recently emerged, driven by a growing number of scientific studies that demonstrate the beneficial effects of these compounds on health [
Microalgae are a natural source of interesting biocompounds. Microalgae are known to produce various therapeutically effective biocompounds that can be obtained from the biomass or released extracellularly into the medium [
Oxidative damage caused by reactive oxygen species to lipids, proteins, and nucleic acids can cause many chronic diseases such as heart disease, atherosclerosis, cancer, and aging. Epidemiological studies have demonstrated an inverse association between the intake of fruits and vegetables and mortality from diseases such as cancer. This phenomenon can be attributed to the antioxidant activity of these foods [
Microalgal biomass is considered a rich natural source of antioxidants, with potential applications in food, cosmetics, and medicine [
Carotenoids and phycocyanins are the pigments most used in scientific research. C-phycocyanin (C-PC) is a blue photosynthetic pigment that belongs to the group of phycobiliproteins found in large quantities in the cyanobacteria, Rhodophyta, and Cryptophyte [
Among the carotenoid compounds,
Polysaccharides represent a class of high value-added components with applications in food, cosmetics, fabrics, stabilizers, emulsifiers, and medicine [
The importance of discovering new compounds with antimicrobial activity is driven by the development of antibiotic resistance in humans due to constant clinical use of antibiotics. Microalgae are an important source of antibiotics with a broad and efficient antibacterial activity [
The antimicrobial activity of extracts from microalgae is related to its lipid composition. The antimicrobial action of microalgae is also noteworthy because of the potential to produce compounds such as
The mechanism of action of fatty acids affects various structures in microorganisms; however cell membranes are the most impacted. Membrane damage most likely leads to a loss of internal substances from the cells, and the entry of harmful components reduces nutrient absorption, in addition to inhibiting cellular respiration. The ability of fatty acids to interfere with bacterial growth depends on both their chain length and the degree of unsaturation. Fatty acids with more than 10 carbon atoms apparently induce lysis of bacterial protoplasts [
Microbial polysaccharides and other biological compounds have antiviral and antimicrobial action. Microalgae produce extracellular sulfated polysaccharide (EPS) with acidic characteristics that has a potential as a therapeutic agent [
The cyanobacterium
Some studies have reported that sulfated polysaccharides derived from microalgae inhibit viral infection, such as encephalomyocarditis virus, Herpes simplex virus types 1 and 2 (HSV1, HSV2), human immunodeficiency virus (HIV), hemorrhagic septicemia in salmonid virus, swine fever virus, and varicella virus [
Inflammation is an immediate reaction to a cell or tissue injury caused by noxious stimuli, such as toxins and pathogens. In this situation, the body recognizes the agents responsible for the attack and attempts to neutralize them as quickly as possible. Inflammation causes redness, swelling, heat, and pain, usually located at the site of infection [
Because of its anti-inflammatory capabilities, microalgal biomass is being considered for applications in tissue engineering for the development of scaffolds, for use in reconstitution of organs and tissues [
Many microalgal polysaccharides possess the ability to modulate the immune system through the activation of macrophage functions and the induction of reactive oxygen species (ROS), nitric oxide (NO), and various other types of cytokines/chemokines [
The PUFAs, especially
Among the pigments with anti-inflammatory activity, fucoxanthin carotenoid found in diatoms [
In humans, the oxidation reactions driven by reactive oxygen species (ROS) can lead to irreversible damage to cellular components, including lipids, proteins, and DNA degradation and/or mutation. Consequently, this damage can lead to several syndromes, such as cardiovascular disease, some cancers, and the degenerative diseases of aging [
Chronic age-related diseases involve oxidative stress and inflammation and their consequences. Chronic inflammation plays a significant role in the mediation of neurodegenerative diseases such as Parkinson’s disease, Alzheimer’s disease, multiple sclerosis, acquired immunodeficiency syndrome (AIDS), and dementia complex [
Natural pigments derived from microalgae (NPs) have neuroprotective properties, being valuable sources as functional ingredients in foods and pharmaceutical products that show efficient action in the treatment and/or prevention of neurodegenerative diseases. Vitamin E has preventive effects for many diseases, such as atherosclerosis and heart disease, as well as neurodegenerative diseases, such as multiple sclerosis [
Carotenoids have great potential benefits to human health, including the treatment of degenerative diseases, such as macular degeneration and cataract development. These compounds act as antioxidants, reducing oxidative damage by ROS. Studies indicated that increased intake of phenols decreased the occurrence of degenerative diseases. Phenolic compounds from microalgae with the potential to fight free radicals have been reported [
Low plasma levels of lutein have also been associated with an increased tendency of myocardial infarction, whereas high intake of lutein was related to a decreased risk of stroke. In addition, high levels of carotenoids with provitamin A activity, including
Scientific findings indicate astaxanthin for multimodal intervention for many forms of degenerative diseases, including cardiovascular diseases, cancer, metabolic syndrome, cognitive impairment, age-related immune dysfunction, stomach and ocular diseases (macular degeneration, cataract, glaucoma, diabetic retinopathy, and retinitis pigmentosa), and skin damage [
The importance of microalgae as sources of functional ingredients has been recognized because of their beneficial health effects. Natural pigments are valuable sources of bioactive compounds. These pigments have various beneficial biological activities such as antioxidant, anticancer, anti-inflammatory, antiobesity, antiangiogenic, and neuroprotective action and are indicated for the treatment or prevention of several chronic diseases [
The antioxidant potential of carotenoid pigments and their ability to prevent cancer, aging, atherosclerosis, coronary heart disease, and degenerative diseases have been described.
Fucoxanthin is considered as a promising dietary and weight loss supplement and for the treatment of obesity. Clinical studies by Abidov et al. [
Microalgae proteins are of great interest as a source of bioactive peptides due to their therapeutic potential in the treatment of various diseases [
The antimicrobial action of certain enzymes (e.g., lysozyme) and immunoglobulins has been reported and recommended for people with different diseases (e.g., Crohn’s disease) due to the existence of formulations with peptides and free amino acids. Studies of the health effects of lysozyme have been reported in the microalgae
The essential fatty acids,
The most studied microalgal lipid compounds are the polyunsaturated fatty acids (PUFAs) docosahexaenoic acid (
Other lipid compounds with interesting bioactive properties are the microalgal sterols. Phytosterols have demonstrated reduction of total cholesterol (LDL) in humans by inhibiting its absorption from the intestine [
The proven ability of microalgae to produce bioactive compounds places these microorganisms in the biotechnological spotlight for applications in various areas of study, especially in the life sciences. The production of microalgal metabolites, which stimulate defense mechanisms in the human body, has spurred intense study of the application of microalgal biomass in various foods and pharmacological and medical products. There is obviously a need for further study of the identified compounds and their activities in the treatment and prevention of various diseases, in addition to an ongoing search for other, as yet undetected, metabolites.
The authors declare that there is no conflict of interests regarding the publication of this paper.
The authors thank the National Counsel of Technological and Scientific Development (CNPq) for the Productivity in Technological Development and Innovative Extension Scholarship.