[Frontiers In Bioscience, Scholar, 9, 319-342, June 1, 2017]

High-value compounds from microalgae with industrial exploitability – A review

Muhammad Bilal1, Tahir Rasheed2, Ishtiaq Ahmed3, Hafiz M.N. Iqbal4

1
State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao
Tong University, Shanghai 200240, China, 2The School of Chemistry and Chemical Engineering, State
Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, Shanghai 200240,
China, 3School of Medical Science, Gold coast campus, Griffith University, Southport QLD 4222,
Australia, 4School of Engineering and Science, Tecnologico de Monterrey, Campus Monterrey, Ave.
Eugenio Garza Sada 2501, Monterrey, N.L., CP 64849, Mexico

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Microalgae and high-value compounds
3.1. Microalgae and pigments – carotenoids and phycobilins
3.2. Microalgae – polysaccharides
3.3. Microalgae – lipids
3.4. Microalgae – fatty acids
4. Microalgae – Biotechnological potentialities
4.1. Microalgae and proteomics
4.2. Microalgae and human nutrition
4.3. Microalgae and nutraceutical
4.4. Microalgae and bio-fertilizer
4.5. Microalgae and cosmeceutical
4.6. Microalgae and biomass
4.7. Microalgae and biofuels
4.8. Microalgae and wastewater treatment
5. Limitations of the algal biotechnology
6. Concluding remarks and future considerations/recommendations
7. Acknowledgements
8. References

1. ABSTRACT

From the past several years, algal compounds which are either impossible or difficult to
biotechnology has gained noticeable interests produce via synthetic routes. In this paper, a range of
among research-based organizations and industrial value-added bioactive compounds from microalgae
sectors. Recent studies have provided considerable with industrial potentialities has been reviewed.
evidence that microalgae-derived bioactive The contribution ended with a critical description of
compounds could play a vital role in bio- and non- the main research gaps and envisioned with future
bio sectors of the modern world. Microalgae-based considerations to progress further in this exciting era
industrial exploitability ranges from basic biomass- of research.
based food and feeds nutraceuticals to high-value
pharmaceuticals, cosmeceuticals, ecological and 2. INTRODUCTION
biomedical applications. With ever increasing scientific
knowledge, social and environmental awareness, bio- Recently, microalgae are gaining
inspired synthesis of microalgae-based green products, considerable attention as a promising source for the
and recent advancements in algal biotechnology will sustainable production of biotechnologically- pertinent
extend the utilization of microalgae into new areas. compounds including fatty acids, carotenoids,
Microalgae offer high biodiversity with an enormous vitamins, and others (1, 2). Microalgae-derived
potential to produce structurally complex yet bioactive secondary metabolites have a great perspective

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for industrial growth and development, since they sodium or copper (14). Chlorophyllins have been used
synthesise bioactive molecules, such as antioxidant, for multi-purposes, such as a dietary supplement and to
antiviral, antibacterial, antifungal, anti-inflammatory, regulate body odor of geriatric patients, etc. (15). Many
antitumor, and antimalarial (3). Despite, numerous studies revealed that chlorophyll and chlorophyllin also
obvious advantages offered by microalgae over plants, exhibit antimutagenic and anticarcinogenic functionality
including rapid growth rates, and lack of competition (16–18).
for resources used for food crops (use of fresh water
and arable lands), the isolation of natural products from Phycobilins are water-soluble proteins.
microalgae remain largely unexplored as compared They can be easily isolated and purified in a high
with terrestrial plants (4). The GRAS (Generally proportion. During photosynthesis, phycobilins play a
recognized as safe) status granted by the United vital role in capturing light. Four classes of phycobilins
States Food Drug Administration (FDA) unlocks the namely (1) allophycocyanin (green-bluish in color), (2)
path wide for the potential application of microalgae as phycocyanin (blue in color), (3) phycoerythrin (purple
an attractive cell factory. This “safe to consume” status in color), and (4) phycoerythrocyanin (orange in color)
is of great importance for industrial perspective since are mainly produced by red algae (Rhodophyta and
it trims downstream purification costs of proteins or Glaucophytes); allophycocyanin (green-bluish),
compounds (5, 6). phycocyanin (blue), phycoerythrin (purple), and
phycoerythrocyanin (orange) (12, 19). Phycobilins
In the past five decades, industrial- are widely used in industrial sectors particularly in
scale cultivation of microalgae has dramatically immunology laboratories due to their characteristic
increased worldwide, and most of the applications absorption properties. Phycobilins are frequently
are commercialized into different sectors (1, 7). To employed as fluorescent markers in molecular biology
date, although genetically unmodified microalgae and immune assays and as fluorescent dyes for
are exploited for synthesizing specific metabolites, microscopy purposes (20). Considerably, most of the
it is believed that strain improvement is mandatory patents published by the United States of America on
to upgrade the feasibility of industrial throughput. these substances are primarily based on fluorescent
Therefore, there is a need to develop novel strains applications, while Japanese has published patents
with desirable features including elevated yield, faster regarding production, purification, and therapeutic
growth as well as low liability to lights and heat, etc. as well as diagnostic purposes (19). The use of
Different approaches such as mutagenesis, adaptive fluorescent probes as labels in immunoassay has
laboratory evolution, and genetic engineering have increased dramatically in current years. Fluorescence
been envisioned as strategies for deciphering algal immunoassay would be of even greater value,
cell factories in the production of bioactive compounds. however, if probes were available with properties
Moreover, synthetic and systems biology perspectives like high solubility, etc. Furthermore, they can easily
are appearing with increased algal productivity of be conjugated to specific molecules so as to be
value added products (8, 9). useful in the context of biological assay procedures.
Figure 1 illustrates fluorescent based applications of
3. MICROALGAE AND HIGH-VALUE Phycobiliproteins.
COMPOUNDS
Carotenoids are fat-soluble in nature with
3.1. Microalgae and Pigments – carotenoids and multi-color appearances i.e. varying form brown, red,
phycobilins and orange to yellow. Together with providing the
photoprotection to the photosynthetic systems, the
Natural pigments contribute a vital part in the carotenoids also perform the function of absorbing
photosynthesis processes along with other pigmentation- light in the UV-visible region, where chlorophyll
based activities in microalgae. Likewise, other biological does not absorb efficiently during photosynthesis.
sources in nature, microalgae also offer numerous This photoprotection mechanism eliminates the
bioactive functionalities including neuroprotective, formation of reactive oxygen species (ROS) making
anticancer, antiangiogenic, antioxidant, anti-obesity, the carotenoids as an excellent antioxidant (21).
and anti-inflammatory, etc. (10, 11). Chlorophylls, The β-carotene, lycopene, astaxanthin, zeaxanthin,
phycobilins, and carotenoids are the three classes of violaxanthin and lutein are the main carotenoids of
pigments that occur in microalgae. Chlorophylls are fat- microalgae. Amongst these, the β-carotene, lutein,
soluble greenish pigments with a porphyrin ring that are and astaxanthin are the most studied ones (22). The
responsible for converting solar energy into chemical β-carotene is a precursor of vitamin A (retinol) with
energy during photosynthesis (12). Most microalgae orange-yellowish color and widely used as a colorant
possess chlorophyll a. However, some other classes for food or nutritional supplement. Natural carotenoids
of algae like Dinophyta (dinoflagellates) contain exhibit remarkable properties as compared to synthetic
chlorophyll b and c (13). Chlorophyllins is a derivative one. Therefore the demand for natural carotenoids
of chlorophyll in which the magnesium is replaced by is increasing day by day. For example, Jayappriyan

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Figure 1. Phycobiliproteins and utility in the fluorescent based application.

et al. (23) reported that Dunaliella salina extracted concentrations, protects the tissues from free radicals
β-carotene causes a high apoptosis rate in prostate (28). Lutein can also prevent atherosclerosis, cataracts,
cancer cells than the synthetic one. In the laboratory, diabetic retinopathy, and retinal degeneration (29).
Alencar and co-workers, (24) quantified β-carotene Several researchers have been investigated the
by cultivating cyanobacteria Spirulina and Spirulina synthesis of lutein by different microalgae, such as
platensis and found 14 times higher β-carotene Muriellopsis sp., Chlorella zofingensis, Chlorella
in the bacteria. In contrast with other carotenoids, protothecosis, Scenedesmus almeriensi (30–32).
Astaxanthin has greater ability to sequester reactive
oxygen free radicals and therefore, it can be used for 3.2. Microalgae – polysaccharides
various diseases, such as diabetes, heart, and chronic
inflammatory diseases as well as in the prevention Economically, algal polysaccharides are the
of some cancers (25, 26). Increased concentration most important products obtained from algae (33).
of secondary carotenoids in the microalgae pointed Figure 2 illustrates metabolic pathways for lipid and
out the improved cell survivability under oxidative carbohydrate synthesis (34). A lot of reviews have
stress generated by certain light conditions, UV-B been presented for the biochemical functioning and
and nutrients (27). Lutein, a pigment yellowish at structural behavior of the polysaccharides (35–38).
lower concentrations and reddish-orange at higher The alginic acid which is also referred to as Alginate is

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Figure 2. Metabolic pathways for lipid and carbohydrate synthesis. A. Outline of the Calvin-Benson and photorespiration cycles. B. Description of storage
carbohydrate and TAG synthesis “Reproduce with permission from” (34).

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a natural polysaccharide that is obtained mainly from and free fatty acids (FFA). Neutral lipids act as a source
30 to 60% of brown algae on a dry weight basis. It of energy for microalgae, while polar lipids are used
accumulates in the plant as gel bodies after it combines for the synthesis of the cell membrane. Nevertheless,
with some minerals from the seawater. Several there are some fatty-acid free components, i.e.,
extraction techniques are used for the extraction of pigments and steroids which are not transformed into
algal polysaccharides, considered as “green” such biodiesel (42). Chlorophyta most studied for biodiesel
as MAE, and EAE (39, 40). Various properties like production comprises Auxenochlorella protothecoides,
antitumor, antiviral, antioxidative, antibacterial, and Chlorella vulgaris, Chlamydomonas rheinhardii,
anti-inflammatory are used for the characterization. The and Dunaliella salina. These species accumulated
extraction of algal polysaccharides and their advance the elevated production of lipids than that of other
identification have proposed various applications divisions presumably due to faster growth. Strains
in different sectors of the modern world including such as Euglenophyta and Dinophyta have the
pharmaceutical, cosmeceuticals, nutraceuticals, and potential to be used for the production of biodiesel
biomedical. Many of the polysaccharides obtained since their lipid production ability is greater than some
from algae including agar, alginate, and carrageenan, Chlorophyta. Zanchett et al. (43) also evaluated the
etc. have been commonly employed as functional biodiesel production aptitude of potentla Cyanophyta
ingredients or stabilizers in pharmaceutical and because of their greater cell growth rate. Nonetheless,
nutraceutical industries. Furthermore, many other some toxic and carcinogenic substances (microcystin)
polysaccharides from seaweeds have potent features are produced during the process. Since fatty acids
for prebiotic exploitability. The algal polysaccharides influence the quality of biodiesel, oxidative stability,
are advantageous for human, animals as well as for and contents of mono, di, and triglycerides, therefore
plants. In an earlier study, Vera et al. (41) investigated evaluating the type of fatty acids is of great importance
various seaweed polysaccharides that includes (44). The lipid metabolism starts with a common initial
ulvans from green algae (Chlorophyta), alginates, pool of molecules consisting of three carbons, such
fucans, laminarin from brown algae (Phaeophyta), as 3-phosphoglycerate (3PG) and glyceraldehyde
and carrageenans, porphyrin from red algae 3-phosphate (GAP) (45) (Figure 3).
(Rhodophyta). In the same study, Vera and co-workers
have observed stimulatory defense response along 3.4. Microalgae – fatty acids
with anti-pathogen, in the plant, the potential of some
algae-derived oligosaccharides. The carboxylic acids with 4.0.-36 carbon
atom chain length are known as fatty acids. Various
Other potential applications of algal-based researchers in microalgae have studied their
polysaccharides have also been reported as good composition. By nature, the fatty acids are categorized
metal ion chelators. It has been shown that seaweed as saturated and unsaturated fatty acids. The fatty
polysaccharides are rich in functional groups that can acids lacking multiple bonds are denoted as saturated
bind microelement ions important in plant nutrition. (SFA), whereas the acids are exhibiting multiple bonds
The chelating properties of polysaccharides from are termed as unsaturated fatty acid (USFA). The
seaweeds can be used in the production of new majority of the fatty acids of microalgae are mono-
formulations-carriers of microelements in fertilizers. saturated (46). As the fatty acids greatly influence
In textile printing, alginic acid is used to thicker the the quality of biodiesel, so their composition plays a
production paste which is then used by fabrics in a vital role in the production of biodiesel. The presence
roller printing or a screen printing equipment. They are of a lot of polyunsaturated fatty acids (PUFA) have a
mostly used for reactive dyes because they combine positive impact on the outflow properties, especially in
chemically well with the cellulose of the fabrics. There cold weathers, but may negatively affect the oxidative
are other thickeners such as starch that react with stability (47). The latter problem can be resolved by
reactive dyes, but this causes lower color yields, and using antioxidants (48). On the other hand, the large
secondary products are not removed easily from the amounts of SFA possess remarkable combustion
fabric, and since alginates do not react with them they properties but can cause problems in the cold outflow
can be removed or washed easily from the textiles. (49). Various factors such as light intensity, nutrient
Although alginate is much more expensive than starch, concentration, carbon source, high salinity, and
however, it is a most convenient choice. temperature may influence the lipid accumulation.
However, stress in microalgae cultivation increases
3.3. Microalgae – lipids lipid accumulation but reduce growth rate, affecting
lipid productivity (50). The cultivation of Chlorella sp.
Lipids exist as polar and neutral molecules with and Scenedesmus sp. in the media containing varying
poor solubility in water but are readily soluble in most nutrients quantities was investigated by Zhan et al.
of the organic solvents. Phospholipids and glycolipids (51). Enhanced lipid accumulation was noted in the
are referred as polar lipids, whereas neutral lipids media containing lesser nutrients in contrasted with
include acyl-glycerides (tri, di- and mono-glycerides) the media having more nutrients for both microalgae.

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Figure 3. Simplified triacylglycerol and starch metabolism in green microalgae. The dashed lines are reactions that take place in the cytosol. Two
possible ways for the formation of TAG molecules are shown following the postulated route in the chloroplasts or over the ER membranes in the cytosol.
3PG, 3-phosphoglycerate; ER, endoplasmic reticulum; TAG, triacylglycerol “Reproduce with permission from” (45).

Grama et al. (52) found an increase in lipid productivity metabolomics, nutrigenomics, proteomics and
of Acutodesmus sp. with increasing light intensity and metagenomic profiling are now being applied
determined the best conditions to be 600uE m2/s with to microalgae to elucidate their genomic and
optimal lipid productivity of 85 mg/L/day. Earlier studies pharmacological interactions with bacteria ­ (54–57).
have also shown that mixed photoautotrophic cultures Transcriptomic-based studies on microalgae furnish
are more valuable and low cost, eliminating the need valuable genomic data that may be used to ascertain
to add organic carbon sources. Therefore, mixed algal species with significant antibiotic potential.
photoautotrophic cultures are more economically Sequencing the transcriptomic data enables the
viable to produce biodiesel than autotrophic or identification and comparison of differentially-
heterotrophic cultures (53). expressed genes in distinct cell populations, or in
response to different environmental factors (58, 59).
4. MICROALGAE – BIOTECHNOLOGICAL Recently, Hovde and coworkers, (60) described the
POTENTIALITIES sequencing of microalgae (Chrysochromulina tobin)
transcriptomic data at seven different time points
Algae have a great potential to produce a over a 24 h light/dark circadian cycle. A considerable
wide range of important biochemical for food, medical difference in gene expression was recorded at all
research and other uses and many exciting and investigated time points for biological processes
important biochemical are yet to be discovered from such as fatty acid biosynthesis. Among the genes
microalgae. Figure 4 illustrates various biotechnological identified, the defense-related genes were found
potentialities of microalgae. to encode novel antibacterial peptides, potential
antibiotics, and antibiotic extrusion proteins. The
4.1. Microalgae and proteomics transcriptomic-based sequencing findings may provide
budding routes for the biosynthesis of therapeutics
More recently developed sophisticated and valued novel metabolites. Algal-extracted
biotechnological approaches such as transcriptomics, compounds with pronounced pharmacological

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Figure 4. Biotechnological application of microalgae in different sectors.

interest were also documented by de Oliveira et al. temperature or food accessibility. Algal biotechnology
(61) from the transcriptomic sequencing of the red may also involve the insertion of a foreign gene
seaweed, Laurencia dendroidea. Explicating the into organisms to produce a new biomolecule or
genomic mechanisms of pharmacologically bioactive expression product having profound antibacterial
metabolites from microalgae offers a potential for potentialities such as terpenes or phlorotannins. The
industrial and biotechnological interventions. chloroplast transformation in Chlamydomonas is the
first and best-studied model system in green algae
Algal biotechnology entails the application since its genome has been completely sequenced
of microalgae as a platform to produce valuable (63). To date, numerous microalgal species have
products for specific purposes (62). This may been transformed in a stable manner. For instance, a
implicate manipulating microalgae cells into luciferase (Luc) and a homologous nitrate reductase
overexpressing a secondary metabolite, or some gene have successfully been turned into Chlorella
compound of pharmacological significance by (64). The recombinant proteins have been produced
exploring environmental parameters such as pH, stably by transforming five heterologous genes into

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the chloroplast of D. tertiolecta (65). Of most recent, either as natural food colorants or nutritional food
Guzman-Zapata et al. (66) carried out the inheritable supplements (72). Functional food oil, rich in fatty
genetic transformation of chloroplasts into green acids and antioxidants, extracted through supercritical
microalga (Chlamydomonas reinhardtii) to potentially CO2 from the microalga Chlorella vulgaris have its use
secrete useful recombinant proteins. in food industry especially for derived seafood (73).
Amongst many efforts dedicated to explicating the
Literature survey revealed that most of health-promoting properties of microalgal biomass, a
the recent advances in genetically engineered generalized immune-modulating effect appears to be
microalgae had been endowed in C. reinhardtii using the most responsible (74). At contemporary, most of the
both chloroplast and nuclear transformation. The C. bio-products launched to serve the health food market
reinhardtii has been demonstrated to be a robust cell are provided as tablets and powder. Nonetheless, algal
factory for the elevated synthesis of many important extracts in various product forms are also developing a
recombinant proteins, including antibodies, vaccines, new market sector for microalgal products.
protein therapeutics, enzymes, and additives, such as
viral protein 28 (VP28), erythropoietin and phytase, etc. 4.3. Microalgae and nutraceutical
A detailed summary of information on the production
of recombination proteins in C. reinhardtii and some Compared with algal powders, functional food
other biotechnologically important microalgae is listed or nutraceuticals produced with microalgal biomass
in Table 1. Apart from C. reinhardtii, several other algae are amazingly much more beneficial and variable,
(including species of Chlorella, Scenedesmus, and thus consolidating health benefits with allurement to
Dunaliella) have also been considered more productive customers. The market of nutraceuticals/functional
and certified as safe. Though the information regarding foods is postulated to be the most dynamic sector
recombinant protein synthesis lacks in these species, in of the food industry and could constitute up to 20%
some cases, however, they can produce recombinant of the whole food market within the next few years.
proteins at the identical levels as C. reinhardtii. For Food supplemented with microalgal biomass might
instance, five chloroplast industrial enzymes and have other positive influences, e.g., prebiotic effects or
recombinant protein in D. tertiolecta and Scenedesmus mineral fortification. Spirulina biomass, as an extract or
dimorphus were expressed as same amounts as in C. processed in pasta, biscuits, and other functional food
reinhardtii (65, 67). Likewise, a monoclonal human IgG products, provokes the functionality of the digestive
antibody against hepatitis B was expressed in the P. tract, e.g., assists in maintaining healthy intestinal
tricornutum (68, 69). Moreover, successful chloroplast bacteria. The supplementation of Spirulina biomass
transformation in Porphytridium spp., Euglena gracilis and aqueous extract led to a 10-folds increase in
and Haematococcus pluvialis have also been reported the growth rate of the lactobacilli compared with the
in earlier studies (70, 71). control. In Germany, food production and distribution
companies (i.e., pasta, bread, yogurt and soft drinks)
4.2. Microalgae and human nutrition have started serious activities to market functional
foods together with the amalgamation of cyanobacteria
Microalgae are an abundant source of and microalgae. Analogous progress can be observed
carbohydrates, protein, enzymes and fiber. In addition in many other developed countries like France, Japan,
to many vitamins and minerals like vitamin A, C, B1, USA, China, and Thailand (75).
B2, B6, niacin, iodine, potassium, iron, calcium and
magnesium are amply found in microalgae. Given a It is estimated that the global nutraceutical
rich source of essential nutrients, they are a major market was valued at around $250 billion in 2014
source of food in Asian countries, in particular like and is predicted to reach around $385 billion by 2020
China, Japan, and Korea. Green microalgae have also due to rapidly increasing consumers demand for
been used as a food source or nutritional supplement in nutraceuticals (76). The global market is dominated by
Asiatic countries for hundreds of years. At present, the the USA, Europe, and Japan who contribute more than
consumption of microalgal-based biomass is restricted 85% of the nutraceutical market. It is anticipated that
to very few taxa, e.g., Spirulina (Arthrospira), Chlorella, these three regional markets will remain at the forefront
Dunaliella and Aphanizomenon with Chlorella and of the nutraceutical industry both as producers and
Spirulina being dominant in the microalgal market, consumers because of increasing awareness, higher
across the globe. During the past decades, microalgal income levels, and a preference for nutraceutical
biomass was extensively used in the health food products, preventive medicine, and self-treatment.
market, with more than 75% of the annual microalgal It has also been found that amongst the consumers
biomass production being utilized for the manufacturing worldwide, 72% were women aged 35 to 49 years with
of powders, tablets, capsules, or pastilles. Moreover, a higher educational level and greater adherence to the
numerous mixtures of microalgae with other health Mediterranean diet pattern than non-consumers (77).
foods can also be found on the market. Microalgae The intake of nutraceutical products also fluctuates
are also incorporated into pasta, snack foods or drinks with lifestyle; the individuals with healthy lifestyles are

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Table 1. Detailed biosynthetic summary of recombinant proteins in several important microalgae

Microalgae Transformation method Expressed genes Products Expression location References

(Chloroplast/Nucleus)

C. reinhardtii Particle bombardment lsc Anti-HSV glycoprotein D Isc Nucleus (108)

C. reinhardtii Particle bombardment gelonin Anti-CD22-gelonin sc Chloroplast (109)

C. reinhardtii Particle bombardment Exotoxin A Anti-CD22-ETA sc Chloroplast (110)

C. reinhardtii Particle bombardment VP1, CTB VP1-CTB Chloroplast (111)

C. reinhardtii Glass beads method E7GGG E7GGG Chloroplast (112)

C. reinhardtii Particle bombardment VEGF VEGF Chloroplast (113)

C. reinhardtii Particle bombardment HMGB1 HMGB1 Chloroplast (113)

C. reinhardtii Particle bombardment 14FN3 14FN3 Chloroplast (113)

C. reinhardtii Particle bombardment metallothionein-2 Metallothionein-2 Chloroplast (114)

C. reinhardtii Particle bombardment Strail TRAIL Chloroplast (115)

C. reinhardtii Particle bombardment apcA and apcB Allophycocyanin Chloroplast (116)

C. reinhardtii Particle bombardment IgG1 lc, hc Anti-PA 83 anthrax IgG1 Chloroplast (117)

C. reinhardtii Glass beads method crEpo Erythropoietin Nucleus (118)

C. ellipsoidea Electroporation mNP-1 mNP-1 Nucleus (119)

M-SAA (bovine mammary-

C. reinhardtii Particle bombardment m-saa Chloroplast (120)
associated serum amyloid)

Swine fever virus (CSFV)

C. reinhardtii Particle bombardment E2 Chloroplast (121)
structural protein

C. reinhardtii Particle bombardment VP28 VP28 Chloroplast (122)

C. reinhardtii Particle bombardment hGAD65 hGAD65 Chloroplast (123)

C. reinhardtii Particle bombardment CTB, D2 CTB-D2 Chloroplast (124)

C. reinhardtii Glass beads method PfMSP1–19 GBSS-PfMSP1–19 Nucleus (107)

C. reinhardtii Glass beads method PbAMA1-C GBSS-PbAMA1-C Nucleus (107)

C. reinhardtii Particle bombardment Pfs25 Pfs25 Chloroplast (125)

C. reinhardtii Particle bombardment Pfs28 Pfs28 Chloroplast (125)

C. reinhardtii Particle bombardment c.r.pfs48/45 c.r.Pfs48/45 Chloroplast (126)

C. reinhardtii Particle bombardment [Link]-pfs25 [Link]-Pfs25 Chloroplast (127)

C. reinhardtii Particle bombardment appA AppA phytase Chloroplast (128)

C. reinhardtii Electroporation xyn1 β-1,4-endoxylanase Nucleus (129)

C. reinhardtii LiAc/PEG fGH Flounder growth hormone Nucleus (130)

C. reinhardtii Glass beads method human Sep15 Human Sep15 protein Nucleus (131)

D. salina Electroporation HBsAg HBsAg Nucleus (132)

D. salina Glass beads method VP28 VP28 Nucleus (133)

[Link] Particle bombardment xylanase/phytase xylanase/phytase Chloroplast (65)

Rubisco small subunit (RbcS)

L. oebiformis Particle bombardment RbcS Nucleus (134)
protein

Porphyridium sp. Particle bombardment AHAS (W492S) acetohydroxyacid synthase Chloroplast (135)

Monoclonal human IgG antibody

[Link] Particle bombardment IgG LC, HC Chloroplast (68)
against HBsAg

[Link] SiC whiskers Gus β-glucoronidase Nucleus (136)

C. reinhardtii Agrobacterium HBcAgII HBcAg-GS-AgII-GS-HBcAg Chloroplast (137)

C. reinhardtii Glass beads method P24 subunit of HIV-1 viral particles Nucleus (138)

C. reinhardtii Particle bombardment CTB:p210 p210 epitope from ApoB100 Chloroplast (139)
C. reinhardtii - Chlamydomonas reinhardtii; C. ellipsoidea - Chlorella ellipsoidea; D. salina - Dunaliella salina; S. microadriaticum - Symbiodinium
microadriaticum; L. amoebiformis - Lotharella amoebiformis; P. tricornutum - Phaeodactylum tricornutum; TSP - total soluble proteins.

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more commonly users of the nutraceutical products to explore new species with unexpected properties.
(78). Marine-based nutraceutical products represent a In the past decade, plant growth regulators obtained
significant portion of the global market and are derived from microalgae attracted considerable researcher’s
from a diverse range of sources providing a myriad attention. Further, the discovery of bioactive substances
of biologically active molecules. These sources, as or extracts which promote germination, leaf or stem
well as the constituent bioactive molecules and their growth or flowering is also of profound importance.
potential applications, are summarized in Table 2. A future trend appears to be the investigation of the
biological potential of microalgal-derived bioactive
4.4. Microalgae and bio-fertilizer products against plant diseases caused by bacteria or
viruses. It is worth noting that microalgae could be a
Microalgae are frequently employed in source of a novel class of plant-protecting biological
agriculture as bio-fertilizers and soil conditioners. substances shortly (75).
The majorities of cyanobacteria exhibit atmospheric
nitrogen fixing capability and thus, are effectively used 4.5. Microalgae and cosmeceutical
as bio-fertilizers. Cyanobacteria play a fundamental
role in the maintenance and building up of soil fertility Microalgae are a biochemically diverse
and consequently enhance crops productivity by acting congregation of chlorophyll-containing microorganisms
as a natural bio-fertilizer. Nitrogen is a crucial limiting with the remarkable capability of oxygenic
factor for plants growth, and deficiency of this element photosynthesis that is largely found in aquatic
could be encountered by the addition of an appropriate environments. The presence of some individual algal
level of fertilizers (39). A diversity of free-living pigments, together with specific pigment concentration
cyanobacteria has now been recognized as efficient is a distinctive feature of each species of microalgae.
components of cyanobacterial-based bio-fertilizers. Its evaluation reflects as an indirect measure of cell
Apart from contributing nitrogen, cyanobacteria also growth, and a parameter to check the trophic level of
positively assist crop plants by generating various waters. Components of algae are frequently used in
growth-promoting substances such as vitamin B12, cosmetics as thickening agents, water-binding agents,
indole-3-acetic acid, indole-3-propionic acid or 3-methyl and antioxidants (73). Several microalga species are
indole, etc. The thermochemical decomposition of exploited in cosmetics industries, particularly in the
biomass to bio-oil, syngas, and charcoal at elevated skin care market, the main ones being Arthrospira and
temperatures (350–700 °C) in the absence of oxygen Chlorella (83). Other typical species that also possess
is referred as pyrolysis (79). This thermal-driven engrossment in cosmetics purposes are Chondrus
conversion process results in the formation of a solid crispus, Mastocarpus stellatus, Ascophyllum nodosum,
charcoal residue called ‘‘biochar’’ from algae that Alaria esculenta, Spirulina platensis, Nannochloropsis
present promising agricultural applications as a bio- oculata, Chlorella vulgaris and Dunaliella salina (73).
fertilizer and for carbon sequestration (80). Biochar can The microalgae-derived extracts can be mainly found
also be effectively used as process fuel in bioenergy in face and skin care products (e.g., anti-aging cream,
conversion. It is deliberated a long-term sink in carbon refreshing care products, emollient and as an anti-
sequestration process, which could be used to reduce irritant in peelers). Microalgae are also exploited in hair
carbon dioxide emissions. Moreover, the biochar care and sun protection bio-products. The commercially
sequestration bestows the perspective to generate a available products and their properties claimed by their
carbon-negative biofuel (81) potentially. companies are a) a protein-rich extract from Arthrospira
repairs the signs of early skin aging, exerts a tightening
Historically, macroalgae are represented effect and prevents stria formation (Protulines,
as soil fertilizer in coastal regions, across the globe. Exsymol S.A.M., Monaco); b) an extract from Chlorella
The rational thought behind this exciting exploitation vulgaris stimulates collagen synthesis in skin, thereby
of macroalgae or macroalgae-extracted residues is supporting tissue regeneration and wrinkle reduction
the increase in water-binding capacity and mineral (Dermochlorella, Codif, St. Malo, France). Recently, two
composition of the soil (82). These interesting properties new products have also been launched by Penta-pharm
are exploited nowadays using liquid biofertilizers (Basel, Switzerland) including, an ingredient from
produced from microalgae with an objective to Nannochloropsis oculata with excellent skin-tightening
avoid erosion and to initiate floral succession (75). properties (Pepha-Tight) and D. salina, which shows the
Previously, the important role of microalgae in the soil ability to markedly stimulate cell proliferation and turn
ecosystem has often been abandoned. The beneficial over and to positively influence the energy metabolism
effects originate not only from the production of of skin (Pepha-Ctive) (83).
polymers for particle adherence and water storage
in soils or nitrogen-fixing but also from alga-derived 4.6. Microalgae and biomass
bioactive compounds which influence higher plants
(82). At present, microalgal biotechnologists pointed Innovativeness for microalgae-based products
out the soil microalgae as a promising research area has recently developed numerous new technical systems

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High-value compounds from microalgae

Table 2. Marine bioactive molecules: sources, applications and health perspectives (2)a

Category Bioactive Applications Major Marine Sources Health Perspectives References

Molecules

Fish (albacore tuna, silver-line

grunt, brown-backed toadfish, Anti-oxidant, anti-
Edible coating in meat
Collagen hake, trout, lingcod, catfish, hypertensive and anti- (140, 141)
industry (e.g., sausages)
rainbow trout, yellow sea bream skin-aging activities.
and common horse mackerel, etc.)

Stabilizer, texturizer, or
Protein and
thickener in ice cream,
Peptides Fish, especially cold-water It has been shown to
jam, yogurt, cream cheese,
Gelatin (Pollock, cod, haddock, hake prevent and treat chronic (142)
margarine, confectionaries,
and cusk) atrophic gastritis
utilized in low-fat foods and
clarifiers

Whipping, suspending or Mollusks, crustaceans, low-fat Anticoagulant and

Albumin (143)
stabilizing agent fish Antioxidant Properties

Gel formation and coatings in Macroalgae, e.g., K. alvarezii, E. Anti-HIV activity and
Carrageenan (144)
the meat and dairy industry denticulatum, and B. gelatinum anticoagulant properties

Red Alga is the largest source

Agar agar Gel formation and food gums of agar like Gelidium, Gracilaria, - (145)
Hypnea, and Gigartina
Poly- Anticoagulant, antiviral,
Saccharides Fucans and Cell walls of brown algae, sea
Nutraceutical supplements antithrombotic, proliferative (146)
fucanoids urchin eggs, sea cucumbers
and anti-inflammatory

Increase dietary fiber,

Gelling agents, edible
Chitin, chitosan, Shrimp, crab, lobster, prawn reduce lipid absorption,
protective films, clarification (147)
and derivatives and krill antitumor, bactericidal and
and de-acidification of fruits
fungicidal activities

Numerous health
benefits (e.g., visual and
Nutraceuticals (fish oil and
neurodevelopment, reduce
Omega-3 fatty capsules), fortification of
Fatty acids Almost all marine sources risk of cardiovascular (148)
acids livestock, feed, and infant
problems, ameliorate
formula
diseases such as arthritis
and hypertension)

They are the most abundant

Active ingredients in the
Phlorotannins polyphenols found in the marine Antioxidant activity (149)
nutraceuticals
brown algae
Phenolic
Dunaliella salina, Sarcina maxima, Vitamin A precursors,
compounds Carotenoids: Natural food colorings,
Chlorella protothecoides, Chlorella antioxidants, anti-
and other β-carotene, and nutraceutical agents, farmed (150)
vulgaris and Haematococcus carcinogenic and anti-
pigments lutein salmon pigmentation
pluvialis inflammatory

Natural food and beverage Anticancer activity, natural

Chlorophylls S. platensis and A. flos-aquae (151)
colorants source of pigmentation

Gastric proteases;
Various fish body viscera like
pepsins, Cold renneting milk and fish
Atlantic cod, carp, harp seals, - (152)
gastricsins and feed digestion aid
and tuna, etc.
chymosins

Preventing unwanted color

Serine and
changes in food products, Crustaceans, mollusks, and
cysteine - (152)
Marine meat tenderizing, curing of short-finned squid
proteases
enzymes Herring, squid fermentation

Atlantic cod, seal, salmon,

Numerous uses in the fats
Lipases sardine, Indian mackerel and red - (152)
and oils industry
sea bream

Creates protein cross-links to Red sea bream, rainbow trout,

Transglutaminase improve rheological properties Atka mackerel, walleye, Pollock - (153)
of gels, i.e., surimi, gelatin liver, and scallop

Vitamins and Minerals

Fat and water perform many essential
Vitamins soluble vitamins, Almost all marine sources. functions in the body, for
Food, Pharma and
and iron, iodine, Seaweeds are rich sources of example, they provide (154)
nutraceutical industries
Minerals manganese, and vitamins and minerals transport inside cells and
zinc also serve as cofactors
during metabolic processes

329 © 1996-2017
High-value compounds from microalgae

Figure 5. The advantages of algal biomass production systems. CCM; carbon concentrating mechanism “Reproduce with permission from” (34).

for biomass production and down-streamed this biomass algal biomass using some novel multidisciplinary
to commercially valuable products such as functional bioconversion technologies. Algae are predominantly
food, feed additive, aquaculture, soil conditioner, responsible for over 50% of photosynthetic throughput
phycocyanin, phycoerythrin, antioxidants, β-carotene, on earth and are promising sunlight cell factories for
etc. For this standpoint, completely controllable and a wide-range of potentially useful biologically active
closed industrial-scale photobioreactors (PBRs) are compounds, but are seldom exploited for commercial
fetching more importance in recent years. However, purposes (84–86). A great variety of biofuel candidates
regardless of an invaluable array of commodity products were proposed to substitute fossil fuels and to
from microalgal biotechnology, the most significant meet the paucity of energy sectors. In this context,
product in consideration of product quantity and economic bioethanol and biodiesel production from terrestrial
impact is still the microalgal biomass itself (75). The plants have received a lot of impetus worldwide as
microalgae-based biomass as a sun-dried or spray-dried potential substitutes (84). However, limited availability
powder or in compressed form as pastilles is regarded of non-edible crops, food versus fuel competition
as the predominant product in microalgal biotechnology. as well as land consumption have criticized these
This biomass is harvested from natural waters or cultures biofuels and resultantly brought much disagreement
in artificial ponds with subsequent separation from the and debate on their sustainability (87). Considering
growth media and drying. Ultimate product of biomass that crisis, it is of profound importance to explore
production is usually a green- or orange-colored powder, new feedstock, suitable for biofuel production, which
which is used in the human health food or animal nutrition does not deplete the edible feedstock resource. Third
both aquaculture and for animal husbandry (75). Figure 5 generation biofuel technology based on algae or
illustrates advantages of algal biomass production cyanobacteria is widely regarded as one of the most
systems. CCM; carbon concentrating mechanism (34). efficient alternative methods to the conventional crops-
based feedstocks. The algae appear to represent
4.7. Microalgae and biofuels the contemporary renewable source of biofuels and
could encounter the global demand for transport fuels
A diverse variety of biofuels such as (88). It is confessing an economically feasible and
bio-oil, bio-diesel, bio-ethanol, bio-methane, bio- environmentally sustainable, renewable biomass for
hydrogen, syngas, and charcoal can be derived from biofuels production (89).

330 © 1996-2017
High-value compounds from microalgae

Advantageously, algae have the aptitude to production, it could generate up to 247 and 37 million
transform almost all of the energy in biomass residuals tons of algal biomass and bio-oil, respectively. Due to
and wastes to methane and hydrogen (90). Certain obvious variations in the composition of wastewater,
algae and cyanobacteria contain high carbohydrate only specific algae may bring about their potential (98).
and lipid contents that can be used as a potential Thus, it is crucial to select strains with an incredible
raw material for bioethanol and biodiesel production, ability to grow in a variety of wastewaters and producing
respectively (91). Moreover, the algal biofuel does not feedstock for renewable and environmentally-friendly
possess any conflict with food production and have biofuels (99).
the potential to satisfy the global transportation fuels
demand. Given practical standpoint, algae are easy to To date, several examples of wastewater
cultivate, can grow with slight or even no effort using treatment by microalgae have been reported in the
water (92). scientific literature. Martinez et al. (100) accomplished
a considerable removal of nitrogen and phosphorus
For bioethanol production using algae as from urban wastewater using the microalgal S.
raw material, the biomass is first grounded, and the obliquus. They succeeded to achieve 98% removal
starch is converted to sugars followed by mixing of phosphorus and a complete removal (100%) of
with water and Saccharomyces cerevisiae yeast ammonium in an agitated culture of 183 h at 25 °C,
at the warm environment in fermenters (93). The respectively. Similarly, Gomez-Villaetal et al. (101)
yeast breaks down the sugars and converts them investigated the cultivation of microalgae S. obliquus
into bioethanol. Microalgae such as C. vulgaris have in artificial wastewater with a total nitrogen reduction
been regarded as a good source of ethanol due to the of 47% and 79% in winter and summer, respectively.
high starch content (37% dry weight) with up to 65% A 72% and 28% removal efficiency of nitrogen and
ethanol conversion efficiency (94). Ueno et al. (95) phosphorus from wastewater was recorded by Aslan
appraised ethanol production in dark fermentation by and Kapdan, (102) using C. vulgaris. Hodaifa et
using green alga Chlorococcum littorale. Under dark al. (103) achieved a 67.4% removal of BOD5 with
anaerobic conditions, after 24 h of dark fermentation S. obliquus cultured in olive-oil based industrial
conditions at 25 °C, about 27% of the cellular starch wastewater. Use of microalgae is advantageous
was decomposed, which was further accelerated to generate photosynthetic oxygen required by
at the elevated reaction temperature. During the bacteria to biodegrade environmental pollutants
fermentation process, acetate, ethanol, hydrogen, such as polycyclic aromatic hydrocarbons (PAHs),
and carbon dioxide were achieved as fermentation phenolic and organic solvents. The oxygen produced
products (96). by microalgae eliminates the need for external
mechanical aeration (97). The blue-green algae
4.8. Microalgae and wastewater treatment Spirulina sp. has been proved as a potential bio-
sorbent of heavy metals (Cr3+, Cd2+, and Cu2+) (104).
The cultivation systems involving microalgae In addition to aforementioned examples, the Chlorella
production and wastewater treatment (e.g. of amino sp., Scenedesmus sp., Spirulina sp., Nannochloris,
acids, enzyme, or food industries wastewaters) B. brauinii and cyanobacterium Phormidium bohneri
seem to be the best options for microalgae growth have been extensively reported microalgae for the
together with alleviating the environmental burden removal of contaminants or pollutants from wastewater
(92). There is an inimitable prospect to carry out (99, 100, 105, 106).
consolidated processing of wastewater treatment and
nutrients supply to algal cultivation using nutrient-rich 5. LIMITATIONS OF THE ALGAL
(nitrogen and phosphorus) effluent streams. Biofuel BIOTECHNOLOGY
production from algal biomass leads to find out a
pathway for the effective elimination of chemical/ A plethora of information is available, as
organic contaminants, heavy metals, and pathogens discussed above, about many potential aspects of algal
from wastewater (97). Wastewater treatment through biotechnology. Nevertheless, considerable critiques
algae offers the opportunity to recycle these nutrients are still outstanding and need to be addressed in future
into algae biomass as a bio-fertilizer and as a studies. In spite of current scientific advancements in
consequence can compensate treatment process algal biotechnology, a substantial research with proven
cost. At the same time, microalgae can alleviate the employability of algal sources is needed in this particular
effects of sewage effluent and nitrogenous industrial line of research. Similarly, many other unsolved
wastes (92). questions are posing a big research gap that needs
to be addressed comprehensively. Major limitations
Most of the used water turns into wastewater and research gaps in algal biotechnology includes but
endangering the environment and causing severe not limited to the, (1) microalgae cell fragility, (2) light,
health hazards as well. Opportunely, if 50% of this CO2, pH and temperature intensity issues, (3) overall
consumed water is made manageable for algae yield variation with different biological sources, (4)

331 © 1996-2017
High-value compounds from microalgae

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Key Words: Microalgae, Value-Added

Compounds, Industrial Exploitation, Review

Send correspondence to: Hafiz M. N. Iqbal,

School of Engineering and Science, Tecnologico
de Monterrey, Campus Monterrey, Ave. Eugenio
Garza Sada 2501, Monterrey, N.L., CP 64849,
Mexico, Tel: 5218183582000 Ext. 5561 Sub-ext.
115, E-mail: [Link]@[Link]

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