Systems Microbiology and Biomanufacturing

https://doi.org/10.1007/s43393-021-00038-8

REVIEW

Emerging industrial applications of microalgae: challenges and future

perspectives
Aswathy Udayan1 · Ashutosh Kumar Pandey1 · Pooja Sharma1 · Nidhin Sreekumar2 · Sunil Kumar1

Received: 22 April 2021 / Revised: 6 June 2021 / Accepted: 8 June 2021

© Jiangnan University 2021

Abstract
Microalgae are unicellular photosynthetic organisms that have been recently attracted potential interests and have applica-
tions in food, nutraceuticals, pharmaceuticals, animal feed, cosmetics, and biofertilizers industry. Microalgae are rich in a
variety of high-value bioactive compounds which have potential benefits on human health and can be used for the prevention
and curing of many disease conditions. But scale-up and safety issues remain a major challenge in the commercialization of
microalgal products in a cost-effective manner. However, techniques have been developed to overcome these challenges and
successfully selling the products derived from microalgae as food, cosmetics and pharmaceutical industries. Microalgae are
rich in many nutrients and can be used for the production of functional food and nutraceuticals, safety and regulatory issues
are major concerns and extensive research is still needed to make microalgae a commercial success in the future. Many
practical difficulties are involved in making the microalgal food industry commercially viable. The present review focuses
on the industrial applications of microalgae and the challenges faced during commercial production.
Graphic abstract

Keywords Microalgae · Functional foods · Nutraceuticals · Pharmaceuticals · Cosmetics

Extended author information available on the last page of the article

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 Systems Microbiology and Biomanufacturing

Introduction antioxidants etc. [2]. For these reasons, microalga has

been extensively used in food, cosmetics, biofuels, feed,
Microalgae are the ancestors of present-day land plants nutraceutical and pharmaceutical industries (Fig. 1) [3–5].
and primary members of the aquatic ecosystem. Micro- It has also been used in bioremediation, ­CO2 mitigation,
algae are unicellular microorganisms capable of pho- bioremediation of wastewater, and biofuel production [6,
tosynthesis and to generate chemical energy from solar 7]. But the production of energy derivatives using micro-
energy. Microalgae are capable of the production of a algae is not cost-efficient if it is not joined with other high-
major amount of oxygen in the atmosphere. These organ- value metabolite production. The major disadvantages of
isms have rapid growth and produce more biomass rich in the commercialization of microalgal products are small
bioactive compounds in comparison with higher plants. market size, high cost of production, low biomass and
Microalgae process the ability to adapt to adverse environ- product accumulation in large-scale cultivation and high
mental conditions, do not compete with agricultural lands regulatory constraints [8] [9]. But recent economic stud-
and can even cultivate in waste or saline water. Since early ies have proved that the development of microalgal indus-
1500 BC, algal biomass has been used as a major dietary tries is a progressing market field. The worldwide market
component and medicine. The first microalgae used as a of microalgal products is expected to exceed $75 million
medicine dates back 2000 years to overcome famine dis- USD in revenues by 2026 (Microalgae market 2020).
ease [1]. Microalgae have the capacity to generate a vari- Over the last few years, microalgal bioactive compounds
ety of high-value bioactive compounds like carbohydrates, have been attracted more funding and research activities.
proteins, lipids, essential fatty acids, pigments, vitamins, The different types of high-value metabolites with nutraceu-
tical and pharmaceutical importance extracted and purified

Pharmaceucals
Cosmecs
Human Nutrion
Funconal Foods
Therapeucs

Cosmecs
Pharmaceucals
Human Nutrion
Nutraceucs
Food Technology
Foods Technology
Funconal Foods Polysaccharides Energy Creaon
Pharmaceucals
Flavorants
Pigments Lipids

Microalgae

Bioacve
Proteins compounds

Human Nutrion Fine chemicals

Supplements Biopolysters Anbiocs
Recombinants Prtns Vaccines
Vaccines Cosmecs
Therapeuc ABs Agrochemicals

Biopolymers
Biodegradable
Plascs

Fig. 1  Industrial applications of microalgae

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Systems Microbiology and Biomanufacturing

from microalgae include polysaccharides, proteins, polyun- Microalgae as major players in food industry
saturated fatty acids, polyphenols, vitamins, minerals, carot-
enoids etc. [10–12]. The metabolites derived from microal- The primary source of protein for food and feed has been
gae have proven roles for the treatment and prevention of plant-based proteins. Microalgae have emerged as an
many disease conditions like diabetes, cardiac, autoimmune, available renewable natural source of protein. More than
rheumatoid arthritis, anemia, obesity, dementia, and other 70% of the world biomass is the food chain basis for these
neurodegenerative diseases [13, 14]. microalgae. Compounds like protein, carbohydrates, and
From literatures, it is evident that microalgae have been lipids are produced. In 1960s, Japan started the first com-
considered as a food supplement from ancient times itself. mercial cultivation of Chlorella [31]. The enrichment of
During AD 1300, people from Mexico have reported to use high-value metabolites in microalgae will improve the
Spirulina as a food ingredient. It is also reported that people growth and development of the algal-based food industry,
from Africa have also included Spirulina in their daily diet. which focuses on the processing and use of microalgae
Population from South America, Mongolia, and China has for novel functional food products (Table 2). While it is
been used Nostoc as a food supplement. In Spain, people calculated that between 200,000 and 800,000 microalgae
prepared a dry cake known as ‘tecuitlatl’ from blue-green exist in nature, but only a few can be used in human nutri-
algae. From ancient times, Spirogyra has been used as a food tion [32]. An innovative unique concept is microalgae
ingredient in countries like India, Burma and Vietnam [15]. as a source of bulk proteins. Microalgae-based proteins,
Japanese people also used edible cyanobacteria to prepare with many benefits over other protein sources commonly
their native food ‘Suizenji-nori’. Hence it is clear that mod- used greatly contributing to satisfy the population and
ern biotechnological developments using microalgae have demand for protein. High-quality proteins are produced by
started years ago. In 1952, the University of Stanford in the Chlorella and Arthrospira, with both species possessing
United States conducted the first Algal mass culture sympo- high content of essential amino acids for human growth
sium which opened a new way for the industrialization and and development (EAAs) [33, 34].
commercialization of microalgae. Microalgae are the source of many useful compounds
In 1960s, Japan has started a company named Nihon in addition to proteins with health advantages, that can
Chlorella for the mass cultivation of Chlorella for food improve the nutrition value of dietary supplements [35].
applications [16]. Then in 1970s, a company named Sosa In addition to a good protein source, Arthrospira, Chlo-
Texcoco S.A has started Arthrospira cultivation facility rella, and Nannochloropsis have also been identified as
in Lake Texcoco, Mexico. [16]. In Asia, 46 large-scale major producers of carbohydrates and lipids [36, 37].
microalgal cultivation factories have started in 1980s pro- GRAS (Generally Recognized as Safe) status is given for
ducing more than 1000 kg of microalgae per month. Then, Arthrospira, Chlorella, Dunaliella, Haematococcus, Schiz-
the large-scale cultivation of Dunaliella salina was started ochytrium, Porphyridium cruentum, and Crypthecodinium
for beta carotene production and became one of the major cohnii [15]. Some products extracted from microalgae are
producers of microalgal metabolites. India also started cul- sold like the phycocyanin blue colorant from Arthrospira,
tivating microalgae in large-scale industries [1]. In recent DHA from C. Cohnii, and β-carotene from Dunaliella
years, there is rapid growth in the algal biotechnology indus- [38]. Even amongst the numerous forms of microalgae-
tries (Table 1). Microalgal biomass production market has compounds, some microalgae with powerful antioxidants
reached about 5000 tons of dry matter/year and has a turno- are possibly the most significant for industrial uses. It is
ver of ~ $1.25 × ­109 USD per year [1]. also possible to incorporate milk products with microal-
But the major disadvantage of large-scale microalgal cul- gae to provide bioactive compounds [39]. Peptides derived
tivation systems is low biomass production and difficulties from microalgae have been linked to health-promoting
in product recovery, which increases the cost of cultivation activities in humans. Moreover, high-value metabolites
and final product prize. Researchers are still focused on the from microalgae also facilitate the growth of the appro-
development of new methods to enhance the production of priate bacteria [40, 41].
biomass from microalgae and decrease the commercial cul- The application of microalgae as food additives would
tivation cost of microalgae [2, 12]. Microalgal high-value not only deliver nutrient value, but will also assist in
metabolites are also used in several industries for the devel- improving sustainability issues, considering the increas-
opment of nutraceuticals, pharmaceuticals, cosmetic prod- ing population and our modern diet, behaviors, and health.
ucts, aquaculture and poultry feed, and as biofertilizers [2]. Recent studies demonstrated the use of microalgae in
Thus, the present study deals with the recent developments gluten-free bread [42]. Including several amino acids,
of algal biotechnology and the emerging industrial applica- Spirulina contains 70% protein by weight and contains
tions of microalgae, the major challenges and future applica- more beta-carotene than that in carrots per unit mass.
tions of microalgal products in the global market.

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Table 1  Companies involved in the industrial production of microalgal food products

Microalgae Natural habitat Cultivation condi- Bioactive compound Application Companies involved References
tions

Chlorella vulgaris Freshwater Autotrophic, mixo- Lutein Dietary supplement, Algae 4 Future [17–20]
trophic and het- feed (A4F) (Portugal)
erotrophic mode of E.I.D Parry (India)
growth Chlorella Co. (Tai-
wan)
Necton (Portugal)
Spirulina platensis Freshwater High alkalinity Phycocyanin Food ingredient, Algae 4 Future [17–22]
food colorant, (A4F) (Portugal)
dietary supple- E.I.D Parry (India)
ment, fluorescent Chlorella Co. (Tai-
markers wan)
Necton (Portugal)
DIC Lifetec (Japan)
Ocean Nutrition
(Canada)
Wonder Labs (USA)
Chlamydomonas sp. Freshwater Mixotrophic and Terpenoids Pharmaceuticals and Algae 4 Future [17, 23]
auxotrophic cosmetics (A4F) (Portugal)
growth
Dunaliella salina Hypersaline water Halophilic Beta carotene Food supplement, BASF (USA) [22, 24–26]
food colorant, Wonder Labs (USA)
pharmaceuticals, Nikken Sohonsa Co.
feed additive (Japan)
Solzyme Inc. (San
Fransisco)
Haematococcus Freshwater Mesophilic, stress Astaxanthin Food supplement, Algatech (Israel) [18, 27–29]
pluvialis conditions feed additive, E.I.D Parry (India)
antioxidant Blue Biotech (Ger-
many)
AstaReal Co.
(Japan)
Labosphaera incisa Freshwater Mesophilic Omega 6 fatty acids Food supplement, Algae 4 Future [17]
(Arachidonic acid) infant formulae (A4F) (Portugal)
Nannochloropsis sp Marine Mesophilic Omega 3 fatty acids Food supplement, Martek biosciences [30]
(Eicosapentaenoic infant formulae, (USA)
acid) pharmaceuticals, Cyanotech (USA)
aquaculture
Phaeodactylum Marine Mesophilic Omega 3 fatty acids Food supplement, Algae 4 Future [17, 27]
tricornutum (Eicosapentaenoic antioxidant, col- (A4F) (Portugal)
acid) ouring agent, feed Algatech (Israel)
additive

Spirulina is also rich in nutrients like vitamin B, phyco- lactating women. Hainan Simai Enterprising Ltd, located
cyanin, chlorophyll, vitamin E, omega 6 fatty acids, and in China is the major producer of Spirulina in the world
several minerals. Because of these properties, Spirulina is [43] and produces 200 tons of dried biomass per year and
reported as the highly consumed microalgae in the world accounts for 10% of the global production.
[43]. Because of all these reasons, WHO has labelled Spir- Chlorella is another protein-rich microalga consumed
ulina as a ‘super food’ and also considered as a ‘space globally. Chlorella contains 60% proteins along with other
food’ by the National Aeronautics and Space Administra- high-value bioactive compounds. Extracts from Chlorella
tion (NASA). It has been reported that Spirulina contains biomass showed effective anticancer, antimicrobial, and
670% more protein than tofu and 180% more calcium than other health-promoting activities [61]. The protein con-
milk [44]. Spirulina is more readily absorbed by the body centrations of these organisms are three times higher than
when consumed in diet and maintains a normal level of that of beef. Chlorella has been mainly consumed as pills,
nutrients and vitamins in the body. It is also considered as tablets, and powder. It is also incorporated in many other
a perfect food for children with malnutrition, pregnant and functional foods like bread, biscuits, noodles, sweets and

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Systems Microbiology and Biomanufacturing

Table 2  Role of microalgae in various functional food products

Name of food product Microalgal species used Addition Benefits References

Biscuit Spirulina platensis 0.3,0.6 and 0.9% Good sensory and nutritional [45]
profiles
Spirulina platensis, Chlorella 2 and 6% w/w High protein, phenolic and anti- [46]
vulgaris, Tetraselmis suecica, oxidant content
Phaeodactylum tricornutum
Isochrysis galbana 1 and 3% w/w High color stability and good [47]
profile of polyunsaturated fatty
acids
Cookies Haematococcus pluvialis Astaxanthin powder: 5, 10 and Lower glycemic response, high [48]
15% w/w phenolic content and antioxi-
dant activity
Chlorella vulgaris 0.5,1, 2 and 3% w/w Increased color, protein and [49]
carbohydrate content
Bread Spirulina fusiformis 1 and 3% w/w Increased protein content [50]
Spirulina platensis 10% w/w Increased protein, calcium, iron [51]
and magnesium content
Isochrysis galbana, Tetraselmis 0.47% w/w Change in bread color and green [52]
suecica, Nannochloropsis yellow tonalities
gaditana, Scenedesmus alm-
eriensis
Processed cheese Chlorella sp. 0.5 and 1% w/w Decreased meltability and hard- [53]
ness, yellowish green color,
improved texture
Yogurt Chlorella sp. 0.25% Chlorella powder and Increased sensory and storage [54]
2.5–10% Chlorella extract properties
powder
Frozen yogurt Spirulina platensis 3 g/L Increased lactic acid produc- [41]
tion and increased nutritional
value of milk. Increased trace
elements, vitamins and other
bioactive compounds
Fermented milk Spirulina platensis 0.1–0.8% Increased survival of acido- [40]
philus-bifidus-thermophilus
(ABT) starter culture and
nutritional quality
Probiotic fermented milks Spirulina platensis 0.3, 0.5 and 0.8% Increased viability and sensory [39]
Chlorella vulgaris characteristics of probiotics
Vegetarian food gels Spirulina and Haematococcus 0.75% w/w Increased gelling and rheological [55]
properties
Spirulina maxima and Dia- 0.1–1% w/w Increased PUFA content and [56]
cronema vlkianum favorable texture characteristics
Pasta Chlorella vulgaris and Spirulina 0.5–2% w/w Increased firmness of pasta, [57]
maxima attractive color (orange and
green), increased nutritional
and sensory qualities
Isochrisis galbana and Dia- 0.5, 1 and 2% w/w Increased omega 3 fatty acid [58]
cronema vlikianum content and high resistance of
pasta to thermal treatment
Spirulina 5, 10, 20 and 100 g w/w Increased protein content, phe- [59]
nolic content and antioxidant
activity
Dunaliella salina 1,2 and 3% w/w Increased protein, iron, calcium, [60]
magnesium and potassium con-
tent. Increased polyunsaturated
and pigment content

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 Systems Microbiology and Biomanufacturing

beer. AlgaVia is the major producer of protein and lipid-rich in animal feeds. EPA productivity of Nannochloropsis is
Chlorella flour. highly dependent on cultivation conditions and researchers
Antioxidants derived from microalgae are more effec- are focused to enrich EPA productivity of Nannochloropsis
tive than other synthetic and plant-based antioxidants. The in an ecofriendly and cost-effective manner [2, 11, 12, 62].
potential antioxidants derived from microalgae are carot- Phaeodactylum tricornutum is also considered for commer-
enoids, polyphenols, phycobiliproteins, and vitamins [62]. cial production of EPA. DHA rich Isochrysis galbana have
Vitamin C is regarded as the major antioxidants produced been incorporated into biscuits for enhancing its nutrient
in chloroplast and is found abundantly in Dunaliella, Chlo- profile [66]. Hens consuming omega 3 fatty acid enriched
rella, Chaetoceros and Skeletonema [63]. In microalgae, the microalgae have been reported to enhance the polyunsatu-
accumulation of antioxidants occurs during their cultivation rated fatty acid content in their egg yolks and is commer-
in closed photoreactors as a mechanism to prevent cell dam- cially profitable [62].
age. Antioxidant activities of microalgal extracts are getting
more attractive in functional foods and also in beverages.
Microalgae can be considered a natural source of food Concerns associated with microalgal food
colorants due to the abundance of photosynthetic pigments industry
present in it; hence, it is widely used as food coloring agents.
Pigments derived from microalgae also have neuroprotec- Application of microalgae either as a direct food supplement
tive, anti-oxidant and hepatoprotective effects and it is used or constituents in food products and dietary supplements
in nutraceutical, pharmaceutical, cosmetic and aquaculture are still in conflict because of the industrial, regulatory and
industries. In Brazil, chlorophyll extracted from Spirulina nutritional considerations [67]. The factors taken into con-
have been used as a natural colorant in food industry. In sideration while using microalgae in the food industry are
poultry feed, consumption of Chlorella vulgaris increases digestion and bioavailability, metal toxicity, allergenicity,
the pigmentation of egg yolk [64]. Dunaliella contains a toxic secondary metabolites, and synthetic compounds,
high amount of beta carotene and it is more readily absorbed cyanotoxins, radioisotopes, contamination of biomass with
in the body when compared to synthetic pigments. Powder pathogens, and safety and regulatory issues [35]
from Dunaliella biomass is commonly used as food and feed
additives [2]. In comparison to other medicinal properties, Digestibility and bioavailability
β-carotene naturally occurs with its all-trans, 9-cis, 13-cis,
and 15-cis isomers [65] Consumption of microalgae rich in Bioavailability can be defined as the combination of bio-
astaxanthin by fish increase the red color of the flesh and activity and bio-accessibility. Bioactivity is the process of
contains high amounts of vitamin E because of its antioxi- uptake of nutrients into the tissues, its physiological effects,
dant activities. Haematococcus pluvialis is the major pro- and subsequent metabolism. The term bio-accessibility
ducer of astaxanthin. refers to the transport of nutrients across the digestive epi-
Microalgal lipids are high-value energy-rich compounds thelium, release of food constituents from the matrix, and
with many health benefits. Omega 3 fatty acids are long the major changes occurred during the digestion process
chain polyunsaturated fatty acids (LC-PUFAs) which have [68]. Most available research works are focused on the
important roles in brain development, memory and learn- short-term in vitro experiments for studying the bioactivity
ing. Docosahexaenoic acid (DHA) and Eicosapentaenoic of algal foods in which the clear idea of the food value of
acid (EPA) are two major omega 3 fatty acids derived from algal nutrients and its composition is limited. Mainly the fate
microalgae. Currently fish and fish-derived oils are consid- and behavior of the food components and nutrients from the
ered as the major sources of omega 3 fatty acids, but micro- algae in the gut is not clearly studied. Also, the data on the
algae are the primary producers of these fatty acids in the biological effects of algal nutrients on the dietary intake and
aquatic ecosystem. Fish derived essential fatty acids have bioactivity of the gut microbiota are lacking. Therefore, it
many practical disadvantages and it contains toxic contami- is indeed necessary to study the digestion and transforma-
nants like mercury. Microalgae can be considered as ecof- tion of microalgae and its subsequent nutrients in the human
riendly and safe sources of DHA and EPA. DHA oil from system.
microalgae is used in pharmaceuticals, infant formulas, baby The process of digestion starts in the mouth with the
food and dietary supplements due to its health-promoting help of salivary amylase. However, the role of saliva from
effects [14]. Martek, USA is the major producer of DHA humans on microalgae and its bioactive metabolites were
from C.cohnii in the form of a single cell oil DHASCO not clearly studied. Unlike the ruminants, humans lack
[2]. Nannochloropsis is the potential candidate for EPA the enzymes to digest polysaccharides in cellulose and
production with emerging industrial applications. It is an hemicellulose and the undigested material is called as
edible microalga which can be used in functional food and dietary fiber. These materials will be moved to the large

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intestine. Cian et al. [73] reported that the carbohydrate Heavy metal toxicity
and proteins from algae that is not processed completely
in the small intestine stimulate the immune responses in The microalgal high-value metabolite synthesis can be
humans indirectly by enhancing the responses gut micro- improved by the uptake of metals but the excessive uptake
biota [69]. Duffy et al. [74] showed important health ben- will cause heavy metal toxicity. There is a conflict in using
efits of microalgal-derived foods on bacterial fermentation microalgae as a food source due to the heavy metal uptake
and digestion [70]. for their growth and metabolite production. However, the
The capacity of gut microbiomes is not similar in all information on how algal metals are bioactive or bio-acces-
humans and the fermentation of consumed algal polysac- sible in human digestion is lacking and there are no proper
charides will be different in humans from different countries. quantification approaches available to study the bioavail-
In Japanese people, the presence of enzymes that degrade ability of metals.
polysaccharides was reported in the Bacteroides plebeius Continuous exposure to the inorganic forms of arsenic
which is absent in Americans [71]. The presence of these (iAs) such as arsenite (As III), arsenate (As V) increases the
enzymes is the result of the horizontal gene transfer (HGT) chances of different types of cancers such as lung, urinary
from a marine bacterium Zobellia galactinvorans which is tract and skin cancers [77]. iAs is present in all types of
reported to present in the surface of the edible red seaweed seafood’s and they enter into the cells with the help of aqua-
‘nori’ [72]. Thomas et al., in 2012 reported HGT as the rea- porins and phosphate transporters [78]. According to the
son specific gene cluster present in the gut microbiota which guidelines of WHO, the permissible concentration of inor-
helps in the digestion of alginates from brown algae [73]. ganic As in potable water is 10 µg L ­ −1 [79]. Over 50 types
Moreover, a study conducted in Spanish people also shows of As were identified in marine food products but the exact
the presence of gut microbes with the enzymes porphyra- As content in marine foods cannot be used to calculate the
nases and agarose 4-glycanohydrolase (agarases) [71]. These potential health impacts on humans because aquatic organ-
differences clearly show the different dietary history, food isms possess efficient systems to detoxify iAs to nontoxic
practices, and gut microbiota which makes the digestibility forms [80]. Fish and mollusks convert iAS to arsenobetaine
and bioavailability of food and dietary products from algae which after consumption by humans excreted as arsenobe-
more complex [74, 75]. Therefore, it is very important to taine which is not toxic [80].
understand the bioavailability of nutrients and functional Algae convert iAs to arsenosugars, and when there is a
foods from microalgae. deficiency of phosphate, iAs again converted into As-phos-
Similar to plants, microalgae have a very complex cell pholipids which helps in the function of the algal cell wall
wall structure and the components are very difficult to membrane [81]. Dimethylarsinic acid (DMA) is the major
degrade. Hence, bioavailability studies have a crucial role type of algal arsenosugars found in humans and listed as
to understand the processing and absorption of metabolites potential carcinogenic agents by IARC 2012 [77]. Raml
and components from food materials. It is also important to et al. [81] reported that invitro trials using human HepG2
study the host and microbiome co-metabolism in the intes- cell lines resulted in DMA toxicity at testing levels higher
tine together with the study of the degree of fermentation in than that normally found in the urine [82]. However, algae
the gut [35]. Vast literature is available on microalgae and (micro and macroalgae) are capable of accumulating As
macroalgae-derived nutraceuticals and functional foods [2]. in comparison with other aquatic organisms [83]. Higher
But there, quantitative analysis on human health and metab- accumulation of As by algal cells will cause toxicity to food
olism is still unknown. The traditional analytical approaches products derived from algae and will be a serious threat to
provide less information about the interaction and regula- human health. Brown macroalgae such as Laminaria sp. and
tion of microbial flora and its fermentation mechanisms. Sargassum sp. are reported to contain a significant amount
The complexity and nature of algal cell wall, presence of of iAS in their cells [84, 85]. Studies conducted by Naka-
soluble fibers, altered metabolite and biomass composition mura et al. (2008), showed that, the uncooked sea weed
based on the harvest season, changes in metabolite profiles Sargassum fusiforme (also known as hijiki) contains high
during environmental variations, differences in food prepara- levels of iAS (60 µg ­g−1 dry wt) in comparison to the cooked
tion and biomass processing methods, anthropogenic factors, hijiki (0–4-2.8 µg ­g−1 [86]. The major concerns regarding
etc. significantly contribute to the bioavailability of nutrients the toxicity of As to humans are the major form of As in the
and functional foods from algae [76]. Future studies using dietary supplement, metabolism of As in specific individuals
improved molecular and genetic methods, xenobiotic ani- and the bioavailability of As on cooking [86, 87]. Nakamura
mal models, studies of enhanced gastrointestinal digestion, et al. (2008) showed that the consumption of iAS at higher
etc. will give new insights on how the bioactive compounds levels would increase the susceptibility to skin cancers [88].
derived from algae currently used in food industries and its Huang et al. [89] reported 3.5–291 g/L of As pollution in a
bioavailability in humans and other animal models. group of Mozambique Tilapia fish in Taiwan, which causes

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the accumulation of iAs in humans via consumption of these palmata (dulse) and Digenia simplex were reported to pro-
fish [89]. Ground water and fertilizers are the two important duce kainic acid. Kainic acid at higher concentrations is
routes through which As is accumulated in the edible micro- neurotoxic, which is often used to make disease models in
algae Spirulina platensis [90]. In addition to this, eutrophi- experimental animals [35]. Safety standards are not available
cation and increasing concentrations of As due to different for humans regarding the consumption of kainic acid [96].
industrial and human activities in the water environment Blue-green algae supplements (BGAS) are widely sold in
also leads to the higher accumulation of As by algae and markets due to their health benefits like weight loss, detoxi-
subsequent toxicity of algal-derived food products. But there fication, enhanced energy, immunity etc. [97]. BGAS are
are only limited reports are available about the toxicity of available in the form of powders, capsules and pills which
As in microalgal food products and its negative effects on are natural in origin and considered as safe. However, the
human health. Wang et al. [91] reported that supplementa- negative effects of BGAS are also reported which include
tion of 150 g/L of As in the cultivation medium of Spirulina nausea, diarrhea, vomiting, gastrointestinal disturbances
platensis exceeded the normal reference range (1.0 mg/kg) etc. Moreover, presence of cyanotoxins is reported in some
proposed by the National Standard of Health Functional BGAS products. Even though, Spirulina is considered non-
Food Products in China [91]. They had also reported that toxic edible microalgae, traces of dihydrohomoanatoxin-
the higher risk of As contamination can be reduced by the a and epoxyanatoxin-a have been reported in some of the
addition of phosphorous to the cultivation medium. Spirulina-based BGAS [98]. Figure 2, shows the side effects
Bromine (Br) toxicity is also a major problem associated of different types of cyanobacterial toxins on human health.
with the intake of foods derived from algae. But its toxic Iwasa et al. [99] reported that consumption of Spirulina-
effects on human health is not well recognized. Boyer et al. associated BGAS can cause liver damage in middle-aged
[92] reported that excessive intake of Br can create many people in Japan [99]. BGAS often reported to contain traces
health problems [92]. In countries like China, Korea, and of microcystins (MCs) which are toxic to humans [100]. Due
Japan, excessive seafood intake including macroalgae have to the public concerns regarding the side effects of BGAS,
shown to increase the Br concentrations of human female more cautionary statements have been amended regarding
subjects [93]. However, future research should be carried the certification of such products in markets. In USA, the
out to study the risk of heavy metal toxicity in algal food tolerable daily intake (TDI) of BGAS is at the level of 1 μg
products and developing strategies to eliminate the threats MCeq ­g−1 and Switzerland allows the daily consumption
to humans and animals on the consumption of algae. Experi- of 2 μg MC L ­ −1 for adults and subsequent lower amounts
ments in terms of all aspects are indeed necessary specifi- for infants and children’s [101]. Based on the average body
cally beyond toxicity tests of in vitro cell cultures and mov- weight i.e., infants (5 kg), children (20 kg) and adults (50 kg)
ing on to animal studies to identify the risk of consuming the can tolerate a maximum consumption of 0.2. 0.8 and 2.4 μg
micro or macroalgae-derived food products. MCs per day respectively [102].
Algal toxins are also reported to cause different poison-
Allergic reactions and toxicity from algal food ing symptoms such as paralytic shellfish poisoning (PSP),
products amnesic shellfish poisoning (ASP), neurotoxic shellfish poi-
soning (NSP), diarrhic shellfish poisoning (DSP) etc. which
Relatively less information is available on the allergic reac- can cause negative effects on human health (Table 3) [103].
tions of algae and related functional food products. Le et al.
[94], reported the anaphylactic reaction for the first time
in a 17-year-old male after the intake of a tablet contain- Applications of microalgae in cosmetics
ing Spirulina [94]. He had developed symptoms of tingling
of lips, angioedema of the face, nausea, abdominal pain, The major advantage of microalgae being used in cosmetic
wheezing, rashes on arms and trunks, and breathing diffi- industries is their capacity to regenerate and adaptation
culties after ingestion of 300 mg Spirulina tablet. However, under adverse environmental conditions by counteracting the
the original details of the Spirulina and its purity were not cell-damaging activities and prevention of free radical for-
mentioned in the tablet. Consumption of native Spirulina mation. These abilities of microalgae are used in cosmetics
with Microcystis and other toxin-producing blue-green algae industries to replace synthetic products with negative effects
caused toxicity in humans. ‘Whole algalin protein’ (wap) on the skin. In cosmetics, microalgae can either directly use
produced from edible microalgae Chlorella protothecoides or can be used based on the activity of bioactive compounds.
by the company Solazyme, Inc. was shown to cause aller- Microalgae have been used in hair care products, products
gies in tested animal models [95]. Kainic acid, a type of used for regeneration, anti-aging and peelers for skin irri-
amino acid which is structurally similar to glutamate can tation [115]. Arthrospira and Chlorella have been used
act as neurotransmitters in the brain. The red algae Palmaria in sunscreen creams and lotions. Major algae used in the

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Systems Microbiology and Biomanufacturing

Fig. 2  Health problems associ- Nervous ssue, Brain

ated with consumption of Immune system
• Anatoxin A
cyanobacterial toxins • Cylindrospermopsin
• Anatoxin a(S)
• Lipopolysaccharides
• Saxitoxins
• Microcysns
• Cyanopeptolins

Gastrointesnal tract,
epithelia
Anabaenolysins
Limnothrixin Lungs
Puwainaphycins • Cylindrospermopsin
• Microcysns
• Nodularins
Liver
• Cylindrospermopsin
• Microcysns
• Nodularins
• Limnothrixin Stomach, Esophagus
• Cylindrospermopsin
• (Microcysns)

Kidneys
• Cylindrospermopsin
• Limnothrixin Small intesne
• Cylindrospermopsin
• Microcysns

Colon
• (Cylindrospermopsin,
in vitro)
• (Microcysn-LR, in
vitro)

production of cosmetics are Arthrospira, Chlorella, Nanno- by ultraviolet rays [2]. Microalgae Odontella aurita also
chloropsis, Dunaliella, Spirulina, Anacystis, Ascophyllum, showed potential free radical scavenging activity to maintain
Alaria, Chondrus, Mastocarpus etc. [116]. These algae help youthful skin [117] (Table 4).
to prevent wrinkle formation, enhances collagen synthesis
and also helps to reduce vascular imperfections (Table 3).
Ocean Pharma company in Germany produced a skin care
product from the extracts of microalgae named ‘Skinicer’ for Therapeutic applications
preventing aging of the skin. Pepha Tight produced by Pen-
tapharma (Switzerland), using extracts of marine microalgae Microalgae are rich in metabolites such as beta-carotene,
Nannochloropsis also used to maintain the youthful proper- astaxanthin, eicosapentaenoic acid, polyphenols, terpenoids
ties of the skin. Phytomer company in France used extracts etc. promoting their role in the pharmaceutical industry
of Chlorella vulgaris for improving natural protection of [118, 119]. These microalgal metabolites and pigments have
skin. The cosmetics industry uses extracts from microalgae gained the attention of researchers and scientists for their
which are high in pigments, PUFAs, phycobiliproteins and potential in pharmaceutical and therapeutic uses. Recently,
carbohydrates which can be used to make lotions, creams the development of genomic and transcriptomic analysis for
and ointments [116]. Mycosporine like amino acids (MAAs) the improved microalgal bioactive compound production
are small natural molecules synthesized by marine microbes with the help of genetic engineering tools has been consid-
as an adaptation for their high sunlight environments. MAAs ered as an emerging field of research [120]. Microalgae are
have good antioxidant properties. MAAs produced from also known to synthesize immunological proteins, such as
Dunaliella, Spiruluna and Chlorella have the potential to monoclonal antibodies and either accumulate them in their
incorporate into sunscreens to reduce the damage induced cytoplasm or release in surrounding media [121].

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 Systems Microbiology and Biomanufacturing

Table 3  Potential toxins from cyanobacteria and its short term and long-term effects on human health
Toxin Producer Short term health effects Long term health effects References

Microcystins Microcystis, Anabaena, Plank- Gastrointestinal (GI) disorders, Tumor promoter and liver [104, 105]
tothrix liver inflammation, hemor- failure leading to death
Nostoc rhage, pneumonia, skin irrita-
Oscillatoria tion and blistering, fever and
Anabaenopsis flu-like symptoms, atypical
pneumonia
Nodularins Nodularia GI disorders, liver inflamma- Cancer and liver damage lead- [106]
tion, hemorrhage, pneumo- ing to death
nia, dermatitis
Saxitoxins Dinoflagellates: Paralytic shell fish poisoning Long term health effects are [107]
Protogonyaulux (PSP), sometimes lead to unknown
Alexandrium, temporary blindness
Gymnodinium,
Pyrodinium,
Cyanobacteria:
Anabaena,
Aphanizomenon
Cylindrospermopsis
Lyngbya
Anatoxins Anabaena, Skin irritations, speaking dif- Paralysis, tremors, convulsions [108]
Aphanizomenon ficulties, lung disorders and cardiac arrhythmia lead-
Cylindrospermopsis ing to death
Lyngbya
Plantothrix, Oscillatoria,
Microcystis
Cylindrospermopsins Cylindrospermopsis GI disorders, liver inflamma- Malaise, Cancer, anorexia and [109]
Aphanizomenon tion, hemorrhage, pneumo- liver damage leading to death
Umezakia nia, dermatitis
Raphidiopsis
Anabaena
Lipopolysaccharides (LPS) Anacystis Skin rashes, gastrointestinal, Long term health effects are [110]
Anabaena respiratory and allergic reac- unknown
Spirulina tions
Microcystis
Oscillatoria
Phormidium
Schizothrix
Beta methyl amino alanines Limnothrix, Daphnia Magna Damage to neurons Potential link to neurodegener- [111, 112]
(BMAAs) Aphanizomenon ative disorders like Alzhei-
mer’s and Parkinson’s
Aplysiatoxins Lyngbya Dermatitis Cancer [113]
Schizothrix
Oscillatoria
Lyngbyatoxin Lyngbya Skin and GI tract disorders [114]

Pharmaceutical proteins production Various analysis has confirmed the efficient expression,
by microalgae secretion into medium and functioning of the recombinant
mAb against MARV [124]. Microalgae lack the machinery
Expression of human CL4 monoclonal antibody (mAb) was for N-glycosylation and it has been also explored for the pro-
carried out with P. tricornutum and was evaluated in vitro duction of immunoglobulin A (IgA) mAb in C. reinhardtii
against the targeted hepatitis B surface antigens [122]. The for countering glycoprotein D of herpes simplex virus [125].
produced mAb was also found to bind to the Fcγ receptors Positive organization of human IgG1 has been performed in
in humans, as confirmed by cellular binding and surface the Chlamydomonas reinhardtii against Bacillus anthracis
plasmon resonance assays [123]. P. tricornutum has also antigen PA83 wherein the antigen was successfully targeted
been used for the expression of recombinant mAb against by the assembled mAb both in cell lines and in animal mod-
Marburg virus (MARV) which is pathogenic to humans. els [126].

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Systems Microbiology and Biomanufacturing

Immunotoxins or toxin-conjugated Abs are hybrid pro- hypertension and even cancer [137, 138]. Polyphenols
teins that are made by the chemical or genetic conjugation obtained from marine algae are hydrophilic and polar
of antibody fragments with eukaryotic toxins [127, 128]. compounds with molecular weight in the range 162 Da to
Microalgae are also able to produce immunotoxins using 650 kDa [139]. Another type of polyphenol is bromophe-
specific mechanisms. These toxin conjugated Abs approach nol, known for their antidiabetic effects. Marine algae from
specific tumor cells, release the toxins, and trigger apop- Rhodomelaceae family are a major source of these polyphe-
tosis by hindering the translation mechanism of the target nols. CYC27 is a synthetic marine bromophenol derivative
cells [129]. C. reinhardtii chloroplast has been used for the extracted from red alga Rhodomela confervoides. CYC27
production of a single-chain variable fragment against the imparts antidiabetic effects by controlling triglyceride and
CD22 antigen of B-cell surface receptor of exotoxin A from cholesterol levels in serum, enhancing insulin sensitivity,
Pseudomonas aeruginosa. To increase the half- life of this and promoting phosphorylation of RNA binding proteins
immunotoxin in serum, human IgG1 domains were assem- [140]. Similar inhibitory effects on serum triglyceride, cho-
bled between αCD22 and PE40 followed by the expression lesterol, and plasma glucose levels are dissplayed by bromo-
of the resultant construct into C. reinhardtii chloroplast, phenol analogue extracted from red alga [141]. HPN inhibits
therefore providing a more stable and functionally efficient PTP1B which is a negative regulator and a potential thera-
immunotoxin [130, 131]. The treatment of live cell lines of peutic target of insulin signaling pathway (Table 5).
Burkitts lymphoma with variable concentrations of different Microalgal polysaccharides contain high quantity of
immunotoxins was conducted to study the lethality of immu- dietary fibers which, if consumed, helps in the preven-
notoxins expressed in microalgae [131]. The outcome sug- tion of many disease conditions [142]. Alginate is a well-
gested the potential inhibition of proliferation of CA-46 and known algal polysaccharide which aids in obesity con-
Ramos cells by αCD22PE40 and αCD22CH32PE40 mol- trol and reduces the absorption of nutrients through gut
ecules whereas without the PE40 toxin αCD22 was unable thereby reducing energy intake and promoting satiation
to restrict the proliferating B or T cells. Moreover, subcu- [143]. Fucoidan, a derivative of fucan (sulfated polysac-
taneous injection of αCD22PE40 and αCD22CH23PE40 charides), is an algal polysaccharide which reportedly
inhibited tumor propagation in mice models [131]. has potential applications in glycemia and lipedema pre-
Erythropoietin from humans had been successfully vention [144]. Fucoidan and alginate are also utilized
expressed in the nuclear region of C. reinhardtii with the for encapsulation and delivery of drugs, such as insulin
activity of hsp70A/rbcS2 [132]. Almost 8 times increase in [145]. Another group of therapeutic metabolites pro-
cell number of Nb2-11 rat lymphoma cell line was observed duced by microalgae are terpenoids, for e.g., Fucoxan-
after 4 days when treated with about 100 ng HGH from thin, known for its anti-oxidant and anti-obesity proper-
the cell extract of modified C. reinhardtii [133]. Trypsin- ties. Restricted accumulation of adipose tissues, regulation
modulating oostatic factor (TMOF) is a hormone produced of lipid metabolism, and enhanced insulin sensitivity are
in mosquito which can restrict trypsin biosynthesis in the some other functions of Fucoxanthin [146]. Fatty acids
organisms’ gut. Chlorella desiccata with the expression extracted from microalgae shows therapeutic potential by
of TMOF can prove to be a lethal tool for mosquito lar- increasing insulin sensitivity and other health promoting
vae since these microalgae are a food source for the larvae effects [147, 148]. Alkaloids from S. thunbergii inhibit the
[134]. The control of the mosquito population by the use of accumulation of lipid by suppressing SREBP-1c, PPARγ
such transgenic microalgae can be considered as an efficient C/EBPα expression [149].
method to control the spread of fatal diseases transmitted
by mosquitoes, such as malaria, dengue and yellow fever
in a cost-efficient manner. Chlamydomonas has been used Microalgae as animal feed
as a candidate for the successful expression of the Human
immuno virus (HIV) protein. Although the effectiveness Many studies are available regarding the utilization of dif-
of the recombinant protein was not evaluated but it has ferent types of microalgae as animal feed. Ever since the
presented opportunities for the development of a micro- population of meat consumers has relatively increased, there
algae-based oral vaccine for AIDS [135]. Another novel has been an increasing need to develop and maintain live-
idea towards the development of an edible vaccine against stock to obtain improved quality and quantity of meat. The
infectious bursal disease (IBD) was introduced when IBD market for meat is constantly growing and the vegetarians
virus protein VP2 (a strong IBD vaccine candidate) was now contribute to only about 21.8% of the world population
successfully expressed into Chlorella pyrenoidosa, an edi- [150, 151]. So, to meet the rising meat demands, microalgae
ble microalga [136]. are now being used as animal feed resulting in improvement
Polyphenols are a class of metabolites investigated ther- in the quality (in some cases quantity as well) of the meat.
apeutic role in diseases, such as diabetes, hyperlipidemia, It has been reported that out of the total microalgae biomass

13
 Systems Microbiology and Biomanufacturing

Table 4  Production of cosmetics from microalgae and their major skincare products and activities [2, 116–118]
Organism Major producers Products Activity

Spirulina Optimum Derma Acidate, (ODA, Skin whitening facial Improves moisture balance of skin, immunity,
Britain), Ferenes cosmetics mask, Algae mask complexion and reduce wrinkles
Spirulina maxima Ocean Pharma (Germany) Skinicer Skin regeneration and natural Protection
Chlorella vulgaris Phytomer (France) Phytomer Strengthens skins natural protection and neutral-
izes inflammation
Nannochloropsis oculata Pentapharm Ltd (Switzerland) Pepha-Tight Improves skin tightening properties
Dunaliella salina Pentapharm Ltd (Switzerland) Pepta-Ctive Stimulates skin proliferation and energy metabo-
lism of skin
Anacystis nidulans Estee Lauder (USA) Photosomes Improves skin immunity and sun protection
Solazyme (France) Algenist
Spirulina platensis Exsymol S.A.M (Monaco) Protulines Prevents early skin ageing and wrinkle formation
Sanatur GmbH (Germany)

Table 5  Potential applications of microalgae in aquaculture and associated health benefits

Microalgal species Bioactive compound Fish Improved characteristics Health benefits References
in fish

Thraustochytrium sp. EPA and DHA Catfish, Atlantic salmon, Increased growth rate, Improved immune [177, 178]
Pacific white shrimp weight gain and flesh system and disease
quality resistance
Chlorella sp. Astaxanthin, omega 3 Freshwater prawns Increased nutritional Increased antioxidant [179, 180]
fatty acids profile activity
Spirulina platensis Protein, Vitamin, Phyco- Tilapia, Carp, Yellow Increased growth and Improved immune [181]
cyanin tail cichlid, Rainbow survival rate system, antioxidant
trout activity and disease
resistance
Nannochloropsis sp. EPA Tilapia, Increased growth, high Immunomodulatory [182, 183]
Pacific white shrimp, digestibility effects, brain and eye
Rainbow trout health
Phaeodactylum tricor- Protein Atlantic salmon Improved growth perfor- Improved intestinal [184]
nutum mance, nutrient profile absorption and immu-
and digestibility nity
Tetraselmis chuii Protein Shrimp Improved antioxidant Enhanced antioxidant [185]
activity activity

produced, about 30% is used as animal feed or in animal feed content, making it a suitable supplement or feed for livestock
preparations [152]. Various species of microalgae, such as [155, 156].
Schizochytrium, Chlorella, Arthrospira, Isochrysis, Porphy-
ridium, Pavlova and Nannochloropsis have been either uti- Feed for cattle
lized as feed or supplemented in animal feed [153]. The fatty
acids, pigments, and other metabolites from microalgae can An increase in omega 3 fatty acids in milk is observed on
ameliorate the feed and enhance the physical and chemical feeding dairy cattle with lipid encapsulated microalgal sup-
characteristics of the meat including its colour and antioxi- plements, with no negative impact on the yield of milk [157].
dant properties. Consumption of microalgae as/in the feed Supplementation with about 10 g algae per kg of dry matter
also elevates animal physiology [33, 154]. Arthrospira plat- feed for dairy cows reduced the content of milk fat and posi-
ensis (Spirulina) is a blue-green microalga frequently used tively altered the fatty acid composition causing increased
in feed supplements for both humans and animals. It is rich conjugated linolenic acid (CLA) and DHA concentrations
in nutrients, such as β- carotene, vitamins B-complex and [158]. Lipid encapsulation of microalgae averts dehydroge-
E, proteins and is highly digestible to the low carbohydrate nation in cattle rumen [157]. Consumption of microalgae

13
Systems Microbiology and Biomanufacturing

supplemented rapeseed feed by lactating cows resulted in an Microalgae in aquaculture

increase in milk yield and energy content along with higher
concentrations of protein and lactose [159]. However, con- Microalgae are considered as potential candidates in aqua-
tradictory results were observed on feeding Holstein cows culture to increase the nutritional value of fish to induce
fed with microalgal biomass [158]. Increase in milk yield specific biological activities. Microalgae are important in
and energy content with more lactose and proteins was also the nutrition of fish larvae during the developmental stages
observed when lactating Damascus goats fed with microal- [173]. Diets rich with microalgae have the ability to fulfill
gae [160]. Change in fatty acid composition with increase the nutritional needs for growth, metabolism and reproduc-
in omega-3 fatty acids had been observed in goats and their tion of bivalve mollusks [174]. Bivalve shellfish cannot
milk with microalgae feed [161]. synthesize omega 3 fatty acids as their own, therefore is
More microbial protein and branched fatty acids were necessary for bivalve shellfish to consume essential omega
observed in the rumen of Bos indicus when the cattle fed on 3 fatty acids for proper growth. The commonly used microal-
tropical grasses supplemented with Spirulina platensis and gal species in aquaculture are Tetraselmis, Chlorella, Isoch-
Chlorella pyrenoidosa [162]. Use of Spirulina as feed sup- rysis, Pavlova, Chaetoceros, Thalassiosira, Nannochlorop-
plement for different breeds of Australian sheep resulted in sis, Phaeodactylum etc. [43, 175]. For use in aquaculture,
the growth and increase in body weight along with an over- microalgae should fulfill certain parameters like no toxic-
all improved physiology of the sheep [163]. Anti-inflam- ity to the fish species, high nutritional content, proper size,
matory properties depending upon the fed dose were shown readily available cell wall etc. for easy digestibility [176].
by Dunaliella tertiolecta when sheep was fed with it [164]. High protein, essential fatty acids and vitamin content are
Feed intake in cattle and other bovine may also reduce by also important parameter for using microalgae in aquacul-
the consumption feed supplemented with microalgae [165]. ture. In aquaculture, bioactive compounds from microalgae
can be divided into three classes. First class includes the
Feed for poultry and pigs use of carbohydrate and protein-rich microalgae to replace
the traditional feed which can reduce the aquaculture cost.
Red algae, such as Porphyra, Gracilaria, Kappaphycus In the second class, antioxidant-rich microalgae were used
and brown algae like Laminaria, Undaria and Hizikia to increase the immunity of aquatic organisms and thereby
fusiforme are traditionally used as food supplements for overcoming the side effects of antibiotics usage. Third class
humans and show potential to be used as animal feed too used for the enhancement of growth of ornamental or special
owing to their rich nutritional profile. Live weight of pigs fish. Astaxanthin-rich microalgae were used to increase the
revealed an increment of up to 10% on feeding upon diet flesh and fish color in the salmon culturing industry.
supplemented with Laminaria digitata [166]. The supple-
mentation of chicken feed with red microalgae Porphy-
ridium sp. carotenoid content which is evident from the Microalgae as fertilizers
darker color of egg yolk along with about 10% reduction in
cholesterol content of the yolk [167]. However, the use of Biofertilizers are the substances that facilitate nutrient
a high concentration of microalgae in feed for a long time availability and uptake by plants. They not only pro-
can impart negative effects especially on the skin color mote plant growth but also prevent entry and invasion by
and egg yolk of poultry animals [152]. More weight gain pathogen and pests as well as aid in the decomposition of
and feed efficiency with reduced intake were observed in organic residues. Microalgal metabolites can be efficiently
broiler chickens while reduced feed intake and higher feed used to produce biofertilizers/biostimulants, which pro-
efficiency along with 7% decrease in body weight and 13% mote the growth and metabolism of higher plants [186,
reduction in average daily weight gain was observed in 187]. Chemical fertilizers that are traditionally used to
pigs feeding upon Desmodesmus sp. supplemented diet improve plant growth are among the major contributor to
[168]. An increase in DHA and EPA content in chicken soil and water pollution. The aim of pollution reduction
egg has been reported at wash out duration with the feed- along with the fulfillment of global food demand has led to
ing of Nannochloropsis gaditana at 5% and 10% concen- huge support in favor of biostimulants and biofertilizers as
tration [169, 170]. Green microalgae Nannochloropsis a cleaner and sustainable alternative in agriculture. They
oceanica with removed fat content showed slight stimula- are safer and cleaner alternatives as they are biodegrad-
tion of protein synthesis in muscles and liver of broiler able and non-toxic. Biostimulant activity is shown by phy-
chickens [171]. When fed to anaemic pigs, these defatted tohormones, such as indole acetic acid, gibberellic acid,
Nannochloropsis oceanica biomass increased haemoglo- cytokinins, abscisic acid, and others which are synthesized
bin in blood and enhanced growth [172]. by microalgae like Nannochloropsis sp., Chlorella sp.,

13
 Systems Microbiology and Biomanufacturing

Scenedesmus sp. etc. [186]. Biofertilizers derived from Conclusion and future perspectives
microalgae should conserve the stimulants present in the
biomass and should satisfy the market parameters and There are several drawbacks of using microalgae large-
nutrient transport [188]. scale industrial applications. Harvesting of microalgae in
Biofertilizers are generally produced by chemical larger scale has several practical limitations. Moreover,
hydrolysis or enzymatic method. Acidic hydrolysis of there are chances of bacterial contamination in microal-
biomass produces biofertilizer but the end product qual- gal culture in open cultivation systems. Such bacteria can
ity is not up to the mark. The enzymatic method is bet- be toxic which affects the growth and survival of aquatic
ter in terms of quality of the final product if an efficient organisms. Therefore, it is indeed necessary to address the
cell disruption method is employed such that no biomass challenges regarding biomass safety, economic viability
residues remain in the end product. Production of micro- and harvesting methods to facilitate the industrialization
algae-based biofertilizers by enzymatic method requires of microalgae-based aquaculture. It is also necessary to
adequate knowledge and selection of enzymes and operat- study the life cycle analysis and economic performance of
ing parameters along with the quality control of the final using microalgae as aquaculture feed in a natural environ-
product as per the stated regulations. ment. Therefore, it is very necessary to study further on
Cyanobacteria promote the soil characteristics in terms the economic and lifecycle analysis as well as the cultiva-
of organic content, nitrogen enrichment, soil moisture, tion of microalgae in a cost-effective manner for future
helps in the aggregation of soil particles, phosphates, etc. applications. There is indeed a wide range of applications
[189]. Cyanobacteria helps to increase the humus content of microalgae in biotechnology. In terms of nutritional
in the soil and will be helpful for the growth of plants by value, microalgal high-value metabolites are on-demand
facilitating proper mixing with soil. Cyanobacteria also but commercial development is still on early stages due
helps to fix nitrogen in the soil and thereby promoting to high production costs, technical difficulties in down-
plant growth by transporting organic and inorganic nutri- stream processing, and sensory and palatability problems
ents from the soil. Natural and anthropogenic activities during the development of functional foods. Microalgal
cause the degradation of biological soil crusts. Recovery nutraceuticals and pharmaceutical production industries
process from the crusts may take a longer time but it can are facing many practical difficulties in terms of success-
be reduced by inoculation of cyanobacteria. ful biomass and product development in a cost effective
Currently, organic fertilizers for small-scale farmers manner. The major problem associated with commercial
have become a problem of economic instability and for microalgal production is low biomass production. Methods
solving this issue many biological approaches and technol- involving mixotrophic cultivation, use of cheap low carbon
ogies play a crucial role which lowers the cost and helps to sources, industrial and municipal wastewater as cultivation
improve the fertility of the soil. Cyanobacteria are consid- medium, and growth-promoting substances can be used to
ered as a very good example of a source of organic biofer- achieve high biomass production. With the development
tilizer which contains naturally occurring ingredients. of efficient large-scale cultivation systems, microalgal
Apart from cyanobacteria with heterocysts, unicel- biotechnology can satisfy the challenging requirements of
lular non-heterocystous cyanobacteria such as, Aphan- food, feed, nutraceuticals, pharmaceuticals, and biofertiliz-
othece, Gloeocaosa, Oscillatoria, and Plectonema has ers. Due to increasing population rates and emerging of
also reported which can be used as biofertilizer [190]. For new diseases, the general nutritional needs for the soci-
the optimum nitrogen fixation process, an inadequate sup- ety are continuously increasing which can be satisfied by
ply of oxygen and dark light is not favorable. Blue-green microalgae. It is also important to study the safety aspects
algae with heterocysts will have light-dependent nitroge- of microalgal food products in a broad manner.
nase enzyme activity and also helps to fix atmospheric
­N2 [190]. Acknowledgements Authors acknowledge CSIR-National Institute for
Some countries like Vietnam, China, and India use Interdisciplinary Science and Technology (CSIR-NIIST), Trivandrum,
India and CSIR-National Environmental Engineering Research Institute
cyanobacteria in the soil as an alternative source of nitro- (CSIR-NEERI), Nagpur, India for facilitating the research activities.
gen for rice cultivation. Apart from nitrogen, it is also
responsible for the availability of phosphorus to the crop Author contributions All authors contributed to the conception,
and plants, because it solubilizes the insoluble form of design, analysis, and drafting of the article. All authors revised the
phosphate [191]. The growth and metabolism of crops paper prior to the submission.
get enhanced by the use of the combination of growth-
promoting bacteria, cyanobacteria. It also regulates the Declarations
concentration of the micronutrients as well as nitrogen,
Conflict of interest The authors declare no conflict of interest.
phosphorus, and potassium content in grains [189].

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Systems Microbiology and Biomanufacturing

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Authors and Affiliations

Aswathy Udayan1 · Ashutosh Kumar Pandey1 · Pooja Sharma1 · Nidhin Sreekumar2 · Sunil Kumar1

2
* Sunil Kumar Accubits Invent, Accubits Technologies Inc.,
s_kumar@neeri.res.in Thiruvananthapuram, Kerala 695 004, India
1
CSIR-National Environmental Engineering Research
Institute (CSIR-NEERI), Nehru Marg, Nagpur,
Maharashtra 440 020, India

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