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Bioactive food compounds from microalgae: an innovative framework on industrial biorefineries
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ScienceDirect Bioactive food compounds from microalgae: an innovative framework on industrial biorefineries Eduardo Jacob-Lopes, Mariana M Maroneze, Mariany C Depra´, Rafaela B Sartori, Rosangela R Dias and Leila Q Zepka Currently, the most important microalgae-based product for use as bioactive food compound is single-cell protein (whole dried biomass) sold directly as dietary supplements. However, chemical specialties, such as pigments and fatty acids derived from microalgae are consolidating their market share of bioactive compounds for use as food coloring, food additive, and food supplement. Also, several emerging bioactive compounds (phycoerythrin, fucoxanthin, beta-glucan, and exocellular polysaccharides), not yet marketed, are shifting their research and development status to achieve commercial exploitation in the coming years. Microalgae-based products are prominent players in the bioactive food compounds industry. In this sense, this work aims to present a current opinion on bioactive food compounds from microalgae through a biorefinery approach. Address Department of Food Science and Technology, Federal University of Santa Maria (UFSM), Roraima Avenue, 1000, 97105-900, Santa Maria, RS, Brazil
Current Opinion in Food Science 2019, 25:1–7 This review comes from a themed issue on Food bioprocessing Edited by Cristiano Ragagnin de Menezes For a complete overview see the Issue and the Editorial Available online 31st December 2018 https://doi.org/10.1016/j.cofs.2018.12.003
supported in the chemical composition of the microalgae biomass (proteins, lipids, and pigments) besides the extracellular compounds (carbohydrates, lipids, and volatile organic compounds) excreted by the cultures [2,3]. The use of microalgae biomass as food is a traditional practice of several ancient people, especially in Asia and North America. Around the 1950s, microalgae were considered a promising candidate for protein supply in the human food chains. Commercial cultures of microalgae were started in the early 1960s (Chlorella) followed by Arthospira in the 1970s. At this stage, the single-cell protein was the main product that targeted the industry, with applications directed to food and prophylactic use. Later, in the 1980s, the pigments production emerged through the cultivation of the Dunaliella and Haematococcus with focus on b-carotene and astaxanthin as food additive and animal feed. More recently, in the early 1990s, started the production of polyunsaturated fatty acids with focus on docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) for use in aquaculture feed and enrichment of nutritional products. Today, commercial facilities for microalgae production are scattered worldwide. Taiwan, Japan, USA, China, Brazil, Spain, Israel, Germany, and Myanmar are the main producers of the microalgal biomass and products derived. The annual production of microalgal biomass dry is about 19 000 ton, generating an estimated USD 5.7 billion [4].
2214-7993/ã 2019 Elsevier Ltd. All rights reserved.
Introduction Microalgae are a commercial terminology without taxonomic value. Microalgae comprise a diverse group of microorganisms with some 72 500 species consistently cataloged. The current taxonomic standards include 16 classes of these organisms. Between these classes, the most abundant are the diatoms (Bacillariophyceae), the green algae (Crysophyceae), and the golden algae (Chrysophyceae). Conversely, the green algae, the cyanobacteria (Cyanophyceae), and the diatoms are the most significant regarding biotechnological exploitation and use [1].
Independent of these technological routes already consolidated, there are, currently, a considerable effort has been made in research and development to produce food commodities from microalgae. However, the most significant and critical barrier to the market deployment of commercially viable algae-based production remains the high production cost, mainly regarding the value of cultivating and downstream processing. Furthermore, in light persisting the low productivity of the processes, the microalgae-based industry will be forced to deeply focus or rely on a multiple-product biorefinery approach [5]. Thus, the primary objective of this review is to compile issues related to the production of food bioactive compounds from microalgae through to biorefinery approach.
Food bioactive compounds from algae There is a global interest in the exploitation of the microalgae-based processes and products, fundamentally www.sciencedirect.com
Microalgae and their extracts represent a vast and unexplored source of compounds with biological activity. Current Opinion in Food Science 2019, 25:1–7
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These compounds show nutraceutical, antimicrobial, anti-inflammatory, anti-aging, aggregative, vasoconstricting, hypocholesterolemic, antioxidant, immunosuppressive, photoprotective, and neurotransmitting activities [6,7]. Although hundreds of these metabolites have been identified in cultures of photosynthetic microorganisms, the induction of synthesis is in most cases unknown, the separation and recovery of the compounds need to be optimized, and thus, the insertion into commercial products depend yet on research and development. Regardless of these limitations, the production of specialty chemicals from microalgae consists of selecting the species and defining the culture conditions, isolating and purifying the target molecule and proving the biological activity through clinical tests, for finally to obtain the approval by the regulatory agencies [8]. Chemically, the compounds with biological activity can be grouped into proteins/enzymes, fatty acids, sterols, pigments, vitamins, alkaloids, mycosporine-like amino acids, and other compounds not included in these classes [3]. The most species of microalgae present levels above 50% protein in dry weight. Some proteins, peptides, and amino acids have biological functions associated with nutritional benefits and human health. Thus, these biopolymers can be used as nutraceuticals or included in functional food formulations. In addition to the hypolipidemic and hypoglycemic properties, the ingestion of microalgae proteins is associated with the reduction of cholesterol and triglyceride levels [9]. Additionally, some proteins of microalgal origin are associated with the stimulation of the production of the hormone cholecystokinin, which regulates the suppression of appetite and, therefore, have been considered in the formulation of functional foods against obesity [10]. At the enzyme level, some metalloenzymes such as superoxide dismutase has been identified in microalgal cells, whose activity is associated with protection against oxidative damage in cells. Finally, some microalgae species can produce the so-called antifreeze proteins (AFPs). These molecules exhibit unique chemical properties because they can bind to ice crystals, prevent recrystallization and protect other proteins from damage. The AFPs extracted from algae can be used for cryopreservation and frozen food preservation. In addition, some AFPs exhibit yet antifungal properties [11]. Several species of microalgae produce high amounts of lipids, including v-3 long-chain fatty acids such as linolenic, eicosapentaenoic (EPA) and docosahexaenoic (DHA) and v-6 fatty acids such as linoleic, gammalinolenic (GLA) and arachidonic (ARA). The importance of these compounds is based on the inability of humans to synthesize some fatty acids, which is why these acids are called essential fatty acids [12]. These compounds, especially v-3 and v-6 are determinant for the integrity of the Current Opinion in Food Science 2019, 25:1–7
tissues where they are incorporated. The GLA finds therapeutic applications and in the formulation of cosmetics by revitalizing the skin and consequently retarding aging. Linoleic and linolenic acids are essential nutrients for the synthesis of prostaglandins, the immune system and other processes related to tissue regeneration. Linoleic acid is also used in the treatment of skin hyperplasias in topical formulations. DHA and EPA are associated with the reduction of the problems associated with cardiovascular effusions, arthritis, and hypertension, and have an important hypolipidemic activity, through the reduction of triglycerides and an increase in high-density lipoprotein cholesterol. DHA acid also acts on the development and functioning of the nervous system. The ARA and EPA acids present aggregative and vasoconstricting action of platelets and anti-aggregative and vasodilator in the endothelium, besides chemotactic action in neutrophils [13,14]. In terms of pigments, microalgae can synthesize up to three classes of these compounds (chlorophylls, carotenoids and phycobiliproteins). The primary application of microalgal pigments is as a food colorant, especially b-carotene, and astaxanthin. Besides, the use of astaxanthin in feeding salmon and trout as a coloring agent is another important market share. Moreover, because of the antioxidant and anti-inflammatory activities of some of these compounds, there are new applications being developed, especially in the cosmetic and cosmeceutical sectors. Finally, the use as non-radioactive fluorescence markers in clinical diagnostics concludes the current application of the microalgae pigments [15]. In addition to vitamin A, microalgal cells are rich in vitamin C, E, K, thiamine, pyridoxine, riboflavin, nicotinic acid, biotin, and tocopherol. These structures have their applications consolidated at the immune system level through antioxidant activity, cell formation and blood coagulation [16,17]. Besides to cholesterol, some species of microalgae produce unconventional sterols such as brassicasterol, campesterol, stigmasterol, and sitosterol. Because of the high levels of sterols, these species have been used in formulating rations for the growth of juveniles, especially oysters. Controversially, although high levels of cholesterol are known to be associated with risks to the cardiovascular system, sterols from marine microalgae appear to exhibit hypocholesterolemic activity in humans [18]. Microalgae polysaccharides are complex and heterogeneous macromolecules, constituted of different monosaccharides, and in some cases of glucuronic acid and sulfate groups. The bioactivity of these molecules may possibily be used as fibers, namely prebiotic and probiotic. In addition, hypolipidemic, hypoglycemic, and antioxidant activities are related to these structures [6]. www.sciencedirect.com
Bioactive food compounds from microalgae: an innovative framework on industrial biorefineries Jacob-Lopes et al.
Lectins are other biomolecules that have been identified especially in Chlorella and Scenedesmus extracts. These compounds are carbohydrate-binding proteins with use in the detection of disease-related alterations of glycan synthesis and as markers in the infectious diagnosis of several parasites. Some companies have developed formulations based on microalgae lectins with the aim of destroying the development of the disease-causing processes where the conventional antibiotics are not effective [19]. Finally, several-specific biomolecules, not included in previous chemical groups, have been identified in the microalgal extracts. Secondary metabolites with antibiotic activity have received a lot of attention. Many of these compounds have unusual and novel structures with activity antibacterial, antifungal, antiviral, and antineoplastic [20]. These antibiotic compounds include the ambigol A, fischambiguine B, ambiguine I isonitrile, pahayokolide A, Kawaguchi peptin B, noscomin, diterpenoid, nostocycline, chlorellin, transphytol ester, hexadecatetraenoic and octadecatetraenoic acids, gambieric acid, karatungiol and okadaic acid [21].
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gain market share in the bioactive molecules segment, initially dominated by synthetic molecules and from animal and vegetal sources [3,8]. Besides the production of the single-cell protein (whole dried biomass), nowadays also specialty chemicals from microalgae are being produced. In general, these biomolecules are less competitive commercially that traditional sources. However, some microalgae-based products have advantages over their competitors, which make their use economically attractive. The synthetic molecules are less effective than natural sources, for specific applications, such as in infant formulas, fish coloring enhancers, and special dietary supplements. Finally, in some cases, no similar alternatives are available. Phycocyanin, for example, is the unique natural blue colorant available for use [16]. Table 1 illustrates the microalgae-based products currently available in a consolidated market.
Considering the microalgae biodiversity, besides the advance in instrumental methods of analysis, the adaptation of conventional methods for algal extracts and development of new analytical methods, it is expected in the next years, the discovery of new bioactive molecules of microalgal origin with potential for use in the nutraceutical industry.
Independent of these commercially consolidated products, there are several new products derived from the microalgae-based processes in different stages of development. Table 2 summarizes these products, categorizing in three specified categories: (i) commercialized pipeline (for products that have been authorized for production in at least one country, but are not yet marketed), (ii) advanced development (for products which multiple field trials and more one proof of concept) and (iii) early development (for products in which there is only one proof of concept).
Current market of bioactive food compounds from microalgae
Capital and operational expenditures of microalgae-based products
The production of microalgae-based products at industrial scale emerged as a commercial opportunity aiming to
Although some microalgae-based products have the long tradition, large-scale commercial production can still be
Table 1 Microalgae-based products that reached a consolidated food and feed market Application
Similar product (conventional source)
Single-cell protein (whole biomass) Spirulina S. platensis, S. pacifica Chlorella C. vulgaris Schizochytrium S. limacinum Aphanizomezon A. flos-aquae
Protein Protein Protein Protein
No No No No
Pigments b-Carotene
D. salina, D. bardawil
Food colorant, feed additive
Astaxanthin Phycocyanin
H. pluvialis S. platensis
Feed additive, food supplement Food colorant
Synthetic forms, Blakeslea trispora, palm fruit, crude palm oil, carrots Synthetic forms Synthetic forms
Nannochloropsis sp., Phaeodactylum tricornutum, Nitzschia sp. Schizochytrium sp., Crypthecodinium cohnii
Food supplement
Fish oil, walnuts
Food supplement
Fish oil, walnuts
Product
Fatty acids Eicosapentaenoic acid (EPA)
Docosahexanoic acid (DHA)
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Microalgae specie
supplement supplement supplement supplement
similar similar similar similar
alternative alternative alternative alternative
Current Opinion in Food Science 2019, 25:1–7
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Table 2 Microalgae-based products in the pipeline Commercialized
Advanced development Early development
Omega-6 oils Cookies holding whole dried microalgae Noodles with whole dried microalgae Phycoerythrin
Whole biomasses Fucoxanthin
Antioxidants Antimicrobials
Beta-glucan
Bulk oil
Exocellular polysaccharides Fatty acids Proteins
Lutein Enzymes Carbohydrates
Adaptated from Enzing et al. [38].
considered an infant industry. Over the last 70 years, almost 75% of the production volume of the microalgaebased products was directed to single-cell protein for use as health food [22]. Table 3 shows the production costs and selling prices of the main commercial microalgaebased-products. Currently, all marketed microalgae-based products are intracellular, and so, the biomass production is the main criterion for the viability of the technological route. In microalgae production, the economics of scale plays a crucial role in the capital (CAPEX) and operational (OPEX) expenditures of the processes, because of the substantially fixed capital expenditures and labour associated. Norsker et al. [23] show that the increase in the scale in 100 times can reduce the production costs at 72%. At present, the low volumes and high production costs of biomass permit exclusively the production of supplements and nutrients for human consumption and specific cases of Table 3 Production costs and selling prices of commercial microalgaebased products Products
Production cost (USD/kg)
Selling price (USD/kg)
Whole biomass Spirulina Chlorella Schizochytrium
2.0 5.0 2.0
8.0 19.0 5.2
Pigments b-Carotene Astaxanthin Phycocyanin
105.0 552.0 46.0
790 2,500 548
Fatty acids EPA DHA
39.0 39.0
100 120
Adapted from: Refs. [25,39,40,24]. The data were corrected for inflation, when needed, and thus, provide a reasonable estimate of the current values.
Current Opinion in Food Science 2019, 25:1–7
the animal feed. The bioactive food compounds from microalgae have specific advantages about similar alternatives, mainly due to a chemical conformation that is more effective for food/feed applications than the competitors, making their use commercially attractive for the food sector, despite the higher production costs [3]. The bulk production of proteins, carbohydrates, and lipids is not yet foreseen in the short run, because this is a market share that requires higher production volumes, and consequently, the boosting of the cost-effective scale-up with dramatic reduction of production costs [24]. In this sense, although there are enormous research and development (R&D) efforts being made by academy, startups, and multinational companies, microalgae-based products are still far from becoming a commodity [25]. Independent on this, some microalgae-based products require intensive downstream processing. This is evident when comparing the production of the single-cell protein (whole biomass) where only drying of the biomass is required, with the production of the pigments and fatty acids. The costs incurred in subsequent downstream processes account for 2–90% of the total expenditure of manufacturing microalgae-based bioproducts, depending on the purity and biochemical properties required [26]. In addition, should be considered, that in general, microalgae-based products have low yield and so, the extraction and purification impact severely in the total production costs (Figure 1). Finally, the microalgae-based processes are generally developed for one-specific application. The approach of the multiple component production or fraction is not yet consolidated in commercial level. There is no market for the leftover biomass after the extraction of the target bioproduct, and here can be the opportunity to mature the microalgae-based industry. Considering the current low productivities and yields of the microalgae-based processes and products, the industry will be forced to shift its focus to a biorefinery approach aiming to fully valorize the microalgal biomass and enable the economically viable co-production of multiple products [27].
Safety and regulatory issues of food compounds from microalgae In the view of the application of microalgae-based products for food/feed, it is fundamental to know their safety. This is a critical point related to this bioresource since that several microalgae species are toxins producers, particularly the belonging to the Cyanophyceae class. Regarding to the regulatory frameworks, the legislations differ substantially in different regions of the world, with regard to the microalgae-based products. While in the United States, Japan and in Brazil the rules are applied to the product, assessing if the final product is safe, the www.sciencedirect.com
Bioactive food compounds from microalgae: an innovative framework on industrial biorefineries Jacob-Lopes et al.
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Figure 1
<1
Novel speciality chemicals
90
β-carotene
85
Production volume (%)
Astaxanthin
10
Docosahexaenoic acid (DHA)
70
Eicosapentaenoic acid (EPA)
20
Single-cell oils
70
Whole biomass
45
2
Downstream expenditure of manufacturing (%)
Phycocyanin
5
Current Opinion in Food Science
Production volume and downstream expenditure manufacturing of microalgae-based products in the current technological scenario. The data were estimated from: Refs. [22,26,35–37].
European regulation focuses on the technology that was employed to obtain the product. Between the microalgae species that reached the commercial level, some already have the GRAS (generally recognized as safe) status, granted by Food and Drug Administration (FDA) that includes the Spirulina/Arthrospira sp., Chlorella sp., Porphyridium cruentum, and Crypthecodinium cohnii. In addition, Haematococcus pluvialis, Phaeodactylum tricornutum, Dunaliella sp., Nannochloropsis sp., Nitzschia sp. and Schizochytrium sp. have their safety aspect classified as ‘no toxins known’. Finally, in terms of microalgae-based products the b-carotene from Dunaliella salina, docosahexaenoic acid from C. cohnii, single-cell oils from Ulkenia sp. and Schizochytrium sp., astaxanthin esters from H. pluvialis are already approved as food ingredients by European Food Safety Authority (EFSA) [28], FDA [29], Ministry of Health, Labor and Welfare of Japan (MHLW) [30], and Brazilian Health Regulatory Agency (Anvisa) [31]. Finally, it should be considered the possibility of use of genetically modified (GM) microalgae. The use of synthetic biology has been considered a strong strategy www.sciencedirect.com
aiming to improve the performance of microalgae-based processes. The United States in its regulation does not make a distinction between genetically modified and conventional foods. Conversely, in Europe, Japan, and Brazil there are additional regulations on food safety and labeling of genetically modified food/feed [32–34].
Final considerations and recommendations The diversity of food bioactive molecules obtained from microalgae makes these micro-organisms a bioresource with full potential of exploitation in the food industry. Regardless of these potentialities, competition with consolidated technological routes, based, for example, on fossil and non-renewable inputs, often makes the microalgae-based processes/products economically unfeasible in the present scenario. In this way, innovative industrial approaches have been proposed and initially implemented to potentialize the technical and economic performance of microalgal-based products. The process integration, process intensification, besides the implementation of the biorrefinery concept have been considered as the main process engineering Current Opinion in Food Science 2019, 25:1–7
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strategies that will allow a wide commercial exploration of processes and products based on microalgae. These new technological routes are oriented to the effective use of industrial resources, based on equipment, materials and processing techniques. The process integration through the recovery and reuse of surpluses energy, mass, water and effluent from industrial processes has been considered one of the most important approaches towards the economical viability of processes and products based on microalgae, especially when the final product is a commodity, that is, produced in high volumes and marketed at low prices. Thus, the use of industrial wastes, mainly wastewater, is an efficient way to contribute nutrients to cultures, with parallel reuse of water. In the same line of action, the use of greenhouse gases from stationary sources of emission of the processes allows the nutrients to be supplied in photosynthetic cultures. This type of integration is highly dependent on the type of industrial waste. The agroindustries, due to the constitutive characteristics of the wastes (reduced level of toxic compounds and inhibitory compounds of microalgal growth), present greater potential for integration. In addition, the process intensification is seen as an alternative that allows for sharp improvements in industrial processing plants. It is related to the overall increase in the efficiency of the production process, by reducing the ratio of equipment size/production capacity, energy consumption, and waste generation. This evolution may result in the extinction of some traditional unit operations and even entire processes. Microalgal biomolecules, in most cases present at low concentrations, only will be commercially viable through of extraction techniques based on process intensification. Finally, the chemical constitution of microalgal biomass has a potential of exploration of multiple products, besides feed and foods, such as fertilizers, fuels, and bulk chemicals. The full exploration of this bioresource, however, requires a refinery approach, in which different operations of pre-treatments, thermo-chemical, biological and catalytic processes in addition to separation operations should be used to obtain products and co-products, allowing the effective use of resources. These three process engineering approaches will allow, in the medium term, the commercial consolidation of microalgae-based processes and products.
Conflict of interest statement Nothing declared.
Acknowledgement Funding for this research was provided by National Council for Scientific and Technological Development (CNPq). Current Opinion in Food Science 2019, 25:1–7
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34. Brazil. Law No 11.105 of Presidency of the Republic. 2005. 35. Tan XB, Lam MK, Uemura Y, Lim JW, Wong CY, Lee KT: Cultivation of microalgae for biodiesel production: a review on upstream and downstream processing. Chin J Chem Eng 2018, 26:17-30. 36. Cuellar-Bermudez SP, Aguilar-Hernandez I, Cardenas-Chavez DL, Ornelas-Soto N, Romero-Ogawa MA, Parra-Saldivar R: Extraction and purification of high-value metabolites from microalgae: essential lipids, astaxanthin and phycobiliproteins. Microbial Biotechnol 2015, 8:190-209. 37. Garcı´a MDCC, Lo´pez CVG, Sevilla JMF, Grima EM: Preparative recovery of carotenoids from microalgal biomass. Microbial Carotenoids. New York, NY: Humana Press; 2018, 107-115. 38. Microalgae-based products for the food and feed sector: an outlook for Europe. JRC Scientific and Policy Reports. Edited by Enzing C, Ploeg M, Barbosa M, Sijtsma L, Vigani M, Parisi C, Rodrı´guez-Cerezo C. 2014. 39. Chauton MS, Reitana KI, Norsker NH, Tvetera˚s R, Kleivdal HT: A techno-economic analysis of industrial production of marine microalgae as a source of EPA and DHA-rich raw material for aquafeed: research challenges and possibilities. Aquaculture 2015, 436:95-103. 40. D’Alessandro EB, Antoniosi Filho NR: Concepts and studies on lipid and pigments of microalgae: a review. Renew Sustain Energy Rev 2016, 58:832-841.
Current Opinion in Food Science 2019, 25:1–7
ScienceDirect Bioactive food compounds from microalgae: an innovative framework on industrial biorefineries Eduardo Jacob-Lopes, Mariana M Maroneze, Mariany C Depra´, Rafaela B Sartori, Rosangela R Dias and Leila Q Zepka Currently, the most important microalgae-based product for use as bioactive food compound is single-cell protein (whole dried biomass) sold directly as dietary supplements. However, chemical specialties, such as pigments and fatty acids derived from microalgae are consolidating their market share of bioactive compounds for use as food coloring, food additive, and food supplement. Also, several emerging bioactive compounds (phycoerythrin, fucoxanthin, beta-glucan, and exocellular polysaccharides), not yet marketed, are shifting their research and development status to achieve commercial exploitation in the coming years. Microalgae-based products are prominent players in the bioactive food compounds industry. In this sense, this work aims to present a current opinion on bioactive food compounds from microalgae through a biorefinery approach. Address Department of Food Science and Technology, Federal University of Santa Maria (UFSM), Roraima Avenue, 1000, 97105-900, Santa Maria, RS, Brazil
Current Opinion in Food Science 2019, 25:1–7 This review comes from a themed issue on Food bioprocessing Edited by Cristiano Ragagnin de Menezes For a complete overview see the Issue and the Editorial Available online 31st December 2018 https://doi.org/10.1016/j.cofs.2018.12.003
supported in the chemical composition of the microalgae biomass (proteins, lipids, and pigments) besides the extracellular compounds (carbohydrates, lipids, and volatile organic compounds) excreted by the cultures [2,3]. The use of microalgae biomass as food is a traditional practice of several ancient people, especially in Asia and North America. Around the 1950s, microalgae were considered a promising candidate for protein supply in the human food chains. Commercial cultures of microalgae were started in the early 1960s (Chlorella) followed by Arthospira in the 1970s. At this stage, the single-cell protein was the main product that targeted the industry, with applications directed to food and prophylactic use. Later, in the 1980s, the pigments production emerged through the cultivation of the Dunaliella and Haematococcus with focus on b-carotene and astaxanthin as food additive and animal feed. More recently, in the early 1990s, started the production of polyunsaturated fatty acids with focus on docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) for use in aquaculture feed and enrichment of nutritional products. Today, commercial facilities for microalgae production are scattered worldwide. Taiwan, Japan, USA, China, Brazil, Spain, Israel, Germany, and Myanmar are the main producers of the microalgal biomass and products derived. The annual production of microalgal biomass dry is about 19 000 ton, generating an estimated USD 5.7 billion [4].
2214-7993/ã 2019 Elsevier Ltd. All rights reserved.
Introduction Microalgae are a commercial terminology without taxonomic value. Microalgae comprise a diverse group of microorganisms with some 72 500 species consistently cataloged. The current taxonomic standards include 16 classes of these organisms. Between these classes, the most abundant are the diatoms (Bacillariophyceae), the green algae (Crysophyceae), and the golden algae (Chrysophyceae). Conversely, the green algae, the cyanobacteria (Cyanophyceae), and the diatoms are the most significant regarding biotechnological exploitation and use [1].
Independent of these technological routes already consolidated, there are, currently, a considerable effort has been made in research and development to produce food commodities from microalgae. However, the most significant and critical barrier to the market deployment of commercially viable algae-based production remains the high production cost, mainly regarding the value of cultivating and downstream processing. Furthermore, in light persisting the low productivity of the processes, the microalgae-based industry will be forced to deeply focus or rely on a multiple-product biorefinery approach [5]. Thus, the primary objective of this review is to compile issues related to the production of food bioactive compounds from microalgae through to biorefinery approach.
Food bioactive compounds from algae There is a global interest in the exploitation of the microalgae-based processes and products, fundamentally www.sciencedirect.com
Microalgae and their extracts represent a vast and unexplored source of compounds with biological activity. Current Opinion in Food Science 2019, 25:1–7
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These compounds show nutraceutical, antimicrobial, anti-inflammatory, anti-aging, aggregative, vasoconstricting, hypocholesterolemic, antioxidant, immunosuppressive, photoprotective, and neurotransmitting activities [6,7]. Although hundreds of these metabolites have been identified in cultures of photosynthetic microorganisms, the induction of synthesis is in most cases unknown, the separation and recovery of the compounds need to be optimized, and thus, the insertion into commercial products depend yet on research and development. Regardless of these limitations, the production of specialty chemicals from microalgae consists of selecting the species and defining the culture conditions, isolating and purifying the target molecule and proving the biological activity through clinical tests, for finally to obtain the approval by the regulatory agencies [8]. Chemically, the compounds with biological activity can be grouped into proteins/enzymes, fatty acids, sterols, pigments, vitamins, alkaloids, mycosporine-like amino acids, and other compounds not included in these classes [3]. The most species of microalgae present levels above 50% protein in dry weight. Some proteins, peptides, and amino acids have biological functions associated with nutritional benefits and human health. Thus, these biopolymers can be used as nutraceuticals or included in functional food formulations. In addition to the hypolipidemic and hypoglycemic properties, the ingestion of microalgae proteins is associated with the reduction of cholesterol and triglyceride levels [9]. Additionally, some proteins of microalgal origin are associated with the stimulation of the production of the hormone cholecystokinin, which regulates the suppression of appetite and, therefore, have been considered in the formulation of functional foods against obesity [10]. At the enzyme level, some metalloenzymes such as superoxide dismutase has been identified in microalgal cells, whose activity is associated with protection against oxidative damage in cells. Finally, some microalgae species can produce the so-called antifreeze proteins (AFPs). These molecules exhibit unique chemical properties because they can bind to ice crystals, prevent recrystallization and protect other proteins from damage. The AFPs extracted from algae can be used for cryopreservation and frozen food preservation. In addition, some AFPs exhibit yet antifungal properties [11]. Several species of microalgae produce high amounts of lipids, including v-3 long-chain fatty acids such as linolenic, eicosapentaenoic (EPA) and docosahexaenoic (DHA) and v-6 fatty acids such as linoleic, gammalinolenic (GLA) and arachidonic (ARA). The importance of these compounds is based on the inability of humans to synthesize some fatty acids, which is why these acids are called essential fatty acids [12]. These compounds, especially v-3 and v-6 are determinant for the integrity of the Current Opinion in Food Science 2019, 25:1–7
tissues where they are incorporated. The GLA finds therapeutic applications and in the formulation of cosmetics by revitalizing the skin and consequently retarding aging. Linoleic and linolenic acids are essential nutrients for the synthesis of prostaglandins, the immune system and other processes related to tissue regeneration. Linoleic acid is also used in the treatment of skin hyperplasias in topical formulations. DHA and EPA are associated with the reduction of the problems associated with cardiovascular effusions, arthritis, and hypertension, and have an important hypolipidemic activity, through the reduction of triglycerides and an increase in high-density lipoprotein cholesterol. DHA acid also acts on the development and functioning of the nervous system. The ARA and EPA acids present aggregative and vasoconstricting action of platelets and anti-aggregative and vasodilator in the endothelium, besides chemotactic action in neutrophils [13,14]. In terms of pigments, microalgae can synthesize up to three classes of these compounds (chlorophylls, carotenoids and phycobiliproteins). The primary application of microalgal pigments is as a food colorant, especially b-carotene, and astaxanthin. Besides, the use of astaxanthin in feeding salmon and trout as a coloring agent is another important market share. Moreover, because of the antioxidant and anti-inflammatory activities of some of these compounds, there are new applications being developed, especially in the cosmetic and cosmeceutical sectors. Finally, the use as non-radioactive fluorescence markers in clinical diagnostics concludes the current application of the microalgae pigments [15]. In addition to vitamin A, microalgal cells are rich in vitamin C, E, K, thiamine, pyridoxine, riboflavin, nicotinic acid, biotin, and tocopherol. These structures have their applications consolidated at the immune system level through antioxidant activity, cell formation and blood coagulation [16,17]. Besides to cholesterol, some species of microalgae produce unconventional sterols such as brassicasterol, campesterol, stigmasterol, and sitosterol. Because of the high levels of sterols, these species have been used in formulating rations for the growth of juveniles, especially oysters. Controversially, although high levels of cholesterol are known to be associated with risks to the cardiovascular system, sterols from marine microalgae appear to exhibit hypocholesterolemic activity in humans [18]. Microalgae polysaccharides are complex and heterogeneous macromolecules, constituted of different monosaccharides, and in some cases of glucuronic acid and sulfate groups. The bioactivity of these molecules may possibily be used as fibers, namely prebiotic and probiotic. In addition, hypolipidemic, hypoglycemic, and antioxidant activities are related to these structures [6]. www.sciencedirect.com
Bioactive food compounds from microalgae: an innovative framework on industrial biorefineries Jacob-Lopes et al.
Lectins are other biomolecules that have been identified especially in Chlorella and Scenedesmus extracts. These compounds are carbohydrate-binding proteins with use in the detection of disease-related alterations of glycan synthesis and as markers in the infectious diagnosis of several parasites. Some companies have developed formulations based on microalgae lectins with the aim of destroying the development of the disease-causing processes where the conventional antibiotics are not effective [19]. Finally, several-specific biomolecules, not included in previous chemical groups, have been identified in the microalgal extracts. Secondary metabolites with antibiotic activity have received a lot of attention. Many of these compounds have unusual and novel structures with activity antibacterial, antifungal, antiviral, and antineoplastic [20]. These antibiotic compounds include the ambigol A, fischambiguine B, ambiguine I isonitrile, pahayokolide A, Kawaguchi peptin B, noscomin, diterpenoid, nostocycline, chlorellin, transphytol ester, hexadecatetraenoic and octadecatetraenoic acids, gambieric acid, karatungiol and okadaic acid [21].
3
gain market share in the bioactive molecules segment, initially dominated by synthetic molecules and from animal and vegetal sources [3,8]. Besides the production of the single-cell protein (whole dried biomass), nowadays also specialty chemicals from microalgae are being produced. In general, these biomolecules are less competitive commercially that traditional sources. However, some microalgae-based products have advantages over their competitors, which make their use economically attractive. The synthetic molecules are less effective than natural sources, for specific applications, such as in infant formulas, fish coloring enhancers, and special dietary supplements. Finally, in some cases, no similar alternatives are available. Phycocyanin, for example, is the unique natural blue colorant available for use [16]. Table 1 illustrates the microalgae-based products currently available in a consolidated market.
Considering the microalgae biodiversity, besides the advance in instrumental methods of analysis, the adaptation of conventional methods for algal extracts and development of new analytical methods, it is expected in the next years, the discovery of new bioactive molecules of microalgal origin with potential for use in the nutraceutical industry.
Independent of these commercially consolidated products, there are several new products derived from the microalgae-based processes in different stages of development. Table 2 summarizes these products, categorizing in three specified categories: (i) commercialized pipeline (for products that have been authorized for production in at least one country, but are not yet marketed), (ii) advanced development (for products which multiple field trials and more one proof of concept) and (iii) early development (for products in which there is only one proof of concept).
Current market of bioactive food compounds from microalgae
Capital and operational expenditures of microalgae-based products
The production of microalgae-based products at industrial scale emerged as a commercial opportunity aiming to
Although some microalgae-based products have the long tradition, large-scale commercial production can still be
Table 1 Microalgae-based products that reached a consolidated food and feed market Application
Similar product (conventional source)
Single-cell protein (whole biomass) Spirulina S. platensis, S. pacifica Chlorella C. vulgaris Schizochytrium S. limacinum Aphanizomezon A. flos-aquae
Protein Protein Protein Protein
No No No No
Pigments b-Carotene
D. salina, D. bardawil
Food colorant, feed additive
Astaxanthin Phycocyanin
H. pluvialis S. platensis
Feed additive, food supplement Food colorant
Synthetic forms, Blakeslea trispora, palm fruit, crude palm oil, carrots Synthetic forms Synthetic forms
Nannochloropsis sp., Phaeodactylum tricornutum, Nitzschia sp. Schizochytrium sp., Crypthecodinium cohnii
Food supplement
Fish oil, walnuts
Food supplement
Fish oil, walnuts
Product
Fatty acids Eicosapentaenoic acid (EPA)
Docosahexanoic acid (DHA)
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Microalgae specie
supplement supplement supplement supplement
similar similar similar similar
alternative alternative alternative alternative
Current Opinion in Food Science 2019, 25:1–7
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Table 2 Microalgae-based products in the pipeline Commercialized
Advanced development Early development
Omega-6 oils Cookies holding whole dried microalgae Noodles with whole dried microalgae Phycoerythrin
Whole biomasses Fucoxanthin
Antioxidants Antimicrobials
Beta-glucan
Bulk oil
Exocellular polysaccharides Fatty acids Proteins
Lutein Enzymes Carbohydrates
Adaptated from Enzing et al. [38].
considered an infant industry. Over the last 70 years, almost 75% of the production volume of the microalgaebased products was directed to single-cell protein for use as health food [22]. Table 3 shows the production costs and selling prices of the main commercial microalgaebased-products. Currently, all marketed microalgae-based products are intracellular, and so, the biomass production is the main criterion for the viability of the technological route. In microalgae production, the economics of scale plays a crucial role in the capital (CAPEX) and operational (OPEX) expenditures of the processes, because of the substantially fixed capital expenditures and labour associated. Norsker et al. [23] show that the increase in the scale in 100 times can reduce the production costs at 72%. At present, the low volumes and high production costs of biomass permit exclusively the production of supplements and nutrients for human consumption and specific cases of Table 3 Production costs and selling prices of commercial microalgaebased products Products
Production cost (USD/kg)
Selling price (USD/kg)
Whole biomass Spirulina Chlorella Schizochytrium
2.0 5.0 2.0
8.0 19.0 5.2
Pigments b-Carotene Astaxanthin Phycocyanin
105.0 552.0 46.0
790 2,500 548
Fatty acids EPA DHA
39.0 39.0
100 120
Adapted from: Refs. [25,39,40,24]. The data were corrected for inflation, when needed, and thus, provide a reasonable estimate of the current values.
Current Opinion in Food Science 2019, 25:1–7
the animal feed. The bioactive food compounds from microalgae have specific advantages about similar alternatives, mainly due to a chemical conformation that is more effective for food/feed applications than the competitors, making their use commercially attractive for the food sector, despite the higher production costs [3]. The bulk production of proteins, carbohydrates, and lipids is not yet foreseen in the short run, because this is a market share that requires higher production volumes, and consequently, the boosting of the cost-effective scale-up with dramatic reduction of production costs [24]. In this sense, although there are enormous research and development (R&D) efforts being made by academy, startups, and multinational companies, microalgae-based products are still far from becoming a commodity [25]. Independent on this, some microalgae-based products require intensive downstream processing. This is evident when comparing the production of the single-cell protein (whole biomass) where only drying of the biomass is required, with the production of the pigments and fatty acids. The costs incurred in subsequent downstream processes account for 2–90% of the total expenditure of manufacturing microalgae-based bioproducts, depending on the purity and biochemical properties required [26]. In addition, should be considered, that in general, microalgae-based products have low yield and so, the extraction and purification impact severely in the total production costs (Figure 1). Finally, the microalgae-based processes are generally developed for one-specific application. The approach of the multiple component production or fraction is not yet consolidated in commercial level. There is no market for the leftover biomass after the extraction of the target bioproduct, and here can be the opportunity to mature the microalgae-based industry. Considering the current low productivities and yields of the microalgae-based processes and products, the industry will be forced to shift its focus to a biorefinery approach aiming to fully valorize the microalgal biomass and enable the economically viable co-production of multiple products [27].
Safety and regulatory issues of food compounds from microalgae In the view of the application of microalgae-based products for food/feed, it is fundamental to know their safety. This is a critical point related to this bioresource since that several microalgae species are toxins producers, particularly the belonging to the Cyanophyceae class. Regarding to the regulatory frameworks, the legislations differ substantially in different regions of the world, with regard to the microalgae-based products. While in the United States, Japan and in Brazil the rules are applied to the product, assessing if the final product is safe, the www.sciencedirect.com
Bioactive food compounds from microalgae: an innovative framework on industrial biorefineries Jacob-Lopes et al.
5
Figure 1
<1
Novel speciality chemicals
90
β-carotene
85
Production volume (%)
Astaxanthin
10
Docosahexaenoic acid (DHA)
70
Eicosapentaenoic acid (EPA)
20
Single-cell oils
70
Whole biomass
45
2
Downstream expenditure of manufacturing (%)
Phycocyanin
5
Current Opinion in Food Science
Production volume and downstream expenditure manufacturing of microalgae-based products in the current technological scenario. The data were estimated from: Refs. [22,26,35–37].
European regulation focuses on the technology that was employed to obtain the product. Between the microalgae species that reached the commercial level, some already have the GRAS (generally recognized as safe) status, granted by Food and Drug Administration (FDA) that includes the Spirulina/Arthrospira sp., Chlorella sp., Porphyridium cruentum, and Crypthecodinium cohnii. In addition, Haematococcus pluvialis, Phaeodactylum tricornutum, Dunaliella sp., Nannochloropsis sp., Nitzschia sp. and Schizochytrium sp. have their safety aspect classified as ‘no toxins known’. Finally, in terms of microalgae-based products the b-carotene from Dunaliella salina, docosahexaenoic acid from C. cohnii, single-cell oils from Ulkenia sp. and Schizochytrium sp., astaxanthin esters from H. pluvialis are already approved as food ingredients by European Food Safety Authority (EFSA) [28], FDA [29], Ministry of Health, Labor and Welfare of Japan (MHLW) [30], and Brazilian Health Regulatory Agency (Anvisa) [31]. Finally, it should be considered the possibility of use of genetically modified (GM) microalgae. The use of synthetic biology has been considered a strong strategy www.sciencedirect.com
aiming to improve the performance of microalgae-based processes. The United States in its regulation does not make a distinction between genetically modified and conventional foods. Conversely, in Europe, Japan, and Brazil there are additional regulations on food safety and labeling of genetically modified food/feed [32–34].
Final considerations and recommendations The diversity of food bioactive molecules obtained from microalgae makes these micro-organisms a bioresource with full potential of exploitation in the food industry. Regardless of these potentialities, competition with consolidated technological routes, based, for example, on fossil and non-renewable inputs, often makes the microalgae-based processes/products economically unfeasible in the present scenario. In this way, innovative industrial approaches have been proposed and initially implemented to potentialize the technical and economic performance of microalgal-based products. The process integration, process intensification, besides the implementation of the biorrefinery concept have been considered as the main process engineering Current Opinion in Food Science 2019, 25:1–7
6 Food bioprocessing
strategies that will allow a wide commercial exploration of processes and products based on microalgae. These new technological routes are oriented to the effective use of industrial resources, based on equipment, materials and processing techniques. The process integration through the recovery and reuse of surpluses energy, mass, water and effluent from industrial processes has been considered one of the most important approaches towards the economical viability of processes and products based on microalgae, especially when the final product is a commodity, that is, produced in high volumes and marketed at low prices. Thus, the use of industrial wastes, mainly wastewater, is an efficient way to contribute nutrients to cultures, with parallel reuse of water. In the same line of action, the use of greenhouse gases from stationary sources of emission of the processes allows the nutrients to be supplied in photosynthetic cultures. This type of integration is highly dependent on the type of industrial waste. The agroindustries, due to the constitutive characteristics of the wastes (reduced level of toxic compounds and inhibitory compounds of microalgal growth), present greater potential for integration. In addition, the process intensification is seen as an alternative that allows for sharp improvements in industrial processing plants. It is related to the overall increase in the efficiency of the production process, by reducing the ratio of equipment size/production capacity, energy consumption, and waste generation. This evolution may result in the extinction of some traditional unit operations and even entire processes. Microalgal biomolecules, in most cases present at low concentrations, only will be commercially viable through of extraction techniques based on process intensification. Finally, the chemical constitution of microalgal biomass has a potential of exploration of multiple products, besides feed and foods, such as fertilizers, fuels, and bulk chemicals. The full exploration of this bioresource, however, requires a refinery approach, in which different operations of pre-treatments, thermo-chemical, biological and catalytic processes in addition to separation operations should be used to obtain products and co-products, allowing the effective use of resources. These three process engineering approaches will allow, in the medium term, the commercial consolidation of microalgae-based processes and products.
Conflict of interest statement Nothing declared.
Acknowledgement Funding for this research was provided by National Council for Scientific and Technological Development (CNPq). Current Opinion in Food Science 2019, 25:1–7
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