Bioresource Technology 304 (2020) 122997

Contents lists available at ScienceDirect

Bioresource Technology
journal homepage: www.elsevier.com/locate/biortech

Review

Potential utilization of bioproducts from microalgae for the quality T

enhancement of natural products
Doris Ying Ying Tanga, Kuan Shiong Khooa, Kit Wayne Chewb, Yang Taoc, Shih-Hsin Hod,
Pau Loke Showa,
⁎

a
Department of Chemical and Environmental Engineering, Faculty of Science and Engineering, University of Nottingham Malaysia, Jalan Broga, Semenyih 43500, Selangor
Darul Ehsan, Malaysia
b
School of Mathematical Sciences, Faculty of Science and Engineering, University of Nottingham Malaysia, Jalan Broga, Semenyih 43500, Selangor Darul Ehsan, Malaysia
c
College of Food Science and Technology, Nanjing Agricultural University, Nanjing 210095, China
d
State Key Laboratory of Urban Water Resource and Environment, School of Environment, Harbin Institute of Technology, Harbin, China

GRAPHICAL ABSTRACT

ARTICLE INFO ABSTRACT

Keywords: Microalgae are autotroph organisms that utilise light energy to synthesize various high-value bioactive com-
Microalgae pounds such as polysaccharides, proteins and lipids. Due to its fast growth rate and capability to survive in harsh
Bioactive compounds environment, microalgae nowadays are applied in various industrial areas. The process of obtaining microalgae-
Cultivation based biomolecules starts with the selection of suitable microalgae strain, cultivation, followed by downstream
Harvesting
processing of the biomass (i.e., pre-treatment, harvesting, extraction and purification). The end products of the
Microalgae biotechnology
processes are biofuels and other valuable bioproducts. Nevertheless, low production yield and high-cost
downstream processes are the emerging bottlenecks which need to be addressed in the upscaling of extracted
compounds from microalgae biomass. To conclude, tremendous efforts are required to overcome these chal-
lenges to revolutionize microalgae into a novel and green factory of different bioactive compounds for industrial
necessities to satisfy and fulfil global demands.

⁎
Corresponding author.
E-mail address: PauLoke.Show@nottingham.edu.my (P.L. Show).

https://doi.org/10.1016/j.biortech.2020.122997
Received 4 January 2020; Received in revised form 4 February 2020; Accepted 8 February 2020
Available online 11 February 2020
0960-8524/ © 2020 Elsevier Ltd. All rights reserved.
D.Y.Y. Tang, et al.
1. Introduction
Due to the soaring of global population growth, there is an increase
in the demand for energy, food, water, drugs and other resources.
Microalgae are one of the most underutilized aquatic organisms and
highly attract the attention of the researchers worldwide to cope with
the high requirements from increased population growth. Microalgae
are a group of single-celled organisms or also referred to as phyto-
plankton (i.e., ‘phyto’=plant, ‘planktos’= made to wander) which can
be categorised by various morphological traits (Hallegraeff, 1988).
Various scientific studies had showed the great potential of microalgae
as a reliable and sustainable feedstock for production of biofuel and
diverse valuable bioresources such as polysaccharides, lipids, proteins,
enzymes, vitamins and carotenoids that can be commercialized in dif-
ferent industries (Barkia et al., 2019; Chew et al., 2017). Approximately
7000 tons of dry algal biomass are produced worldwide annually and
the global market for algae biomass is worth between USD 3.8 to 5.4
billion (Brasil et al., 2017). This statistics showed that the microalgae
industry is gaining popularity worldwide and can be utilised ex-
tensively through the incorporation into industrial products for dif-
ferent sectors in the future. There are some features possessed by mi-
croalgae that enable it to be exploited widely such as fast growth rate,
simple cultivation requirements (i.e., require water, sunlight, carbon
dioxide (CO2)) and the ability to survive in harsh conditions.
The process of extracting microalgae-based biomolecules from the
biomass starts with the selection of appropriate microalgae strain as
well as cultivation condition and followed by downstream processing of
the biomass (e.g., pre-treatment, harvesting, extraction and purifica-
tion). Biofuels and bioproducts are the end products of the process. A
successful cultivation method refers to the method at which the mi-
croalgae are cultivated in pilot scale to produce large amount of bio-
mass and in turn synthesize a large quantity of high-valuable com-
pounds. Microalgae can be cultivated in batch, fed-batch or
continuously in open- or closed-systems with different cultivation
modes. Once the microalgae reached its mature stage, harvesting,
comprising of chemical, biological, mechanical or electrical methods, is
an important step to separate the microalgae biomass from the culture
medium. This allows an efficient extraction and purification of high-
value compounds from the microalgae biomass for further processing.
Today, the emerging health issues such as allergic reaction and
hyperactivity have arise from the use of synthetic compounds in food,
skin care products and pharmaceutical products. Therefore, consumers
nowadays tend to use natural products produced from the natural re-
sources that are non-toxic, and one example is microalgae. There are
emerging microalgae-based bioproducts, derived from Chlorella sp. and
Spirulina sp., on the market from different industry sectors, such as food
and beverages, pharmaceutical nutraceutical and dietary supplements.
Nevertheless, the challenges associated in utilizing the high-value
compounds from the microalgae biomass in a large scale still remains
impractical caused by the high economic cost and immaturity in the
upstream and downstream processing of microalgae biomass in the
aspects of cultivation system, culture conditions, bioreactor design,
harvesting techniques, extraction and purification steps. The food,
cosmetics and skin care manufacturers must also pay attention to the
safety and toxicity of the chemicals used for the cultivation, harvesting
and purification of the compounds from the microalgae biomass. The
non-clinical and clinical research on the application of the microalgae-
based products in the food, pharmaceutical and nutraceutical areas are
limited (Caporgno and Mathys, 2018). Hence, researchers need to find a
solution to fill the gaps of these challenges in order to scale-up and
commercialize the production of high value products from the micro-
algal biomass.
This review aims to provide insights into the capability and poten-
tial of the microalgae in synthesizing high-value compounds for the
incorporation into natural products in different industries. The review
also highlighted the health beneficial properties of various bioactive
2
Bioresource Technology 304 (2020) 122997
compounds produced by microalgae. The attention is drawn to the in-
corporation of these compounds into different industrial areas, for in-
stance, food, drugs, cosmetics and transportation to enhance the nu-
tritional values or functions. Besides, the cultivation of microalgae in
terms of type of systems, methods and conditions as well as different
harvesting techniques were also evaluated. Lastly, this review ad-
dressed the associated challenges confronted by the utilisation of mi-
croalgae in different industries in large scale and the possible future
works to resolve these challenges.
2. Significant bioproducts obtained from microalgae
Microalgae have produced various biocompounds in different pro-
portion that have the commercial interest and have been exploited for
the use in food, aquaculture, wastewater management, transportation,
nutraceutical, pharmaceutical, cosmetics and personal care industries.
In the aquaculture sector, microalgae biomass used for feeding larvae
can reach the market prices exceeding 100 €/kg but the global pro-
duction capacity of microalgae biomass is only approximately 20–30 kt
annually (Fernández et al., 2019). Some examples of microalgae-pro-
duced bioactive compounds including lipids, peptides or amino acids,
antioxidants, polysaccharides and pigments (Singh et al., 2020).
2.1. Carotenoids and pigments
Microalgae can synthesize large quantities of carotenoids that act as
colourant and food supplements such as β-carotene, astaxanthin, can-
thaxanthin and phycobiliproteins. Microalgae have become an attrac-
tive option to be exploited in industries as a source of natural colourant
and supplement due to the emerging of health safety issues caused by
synthetic products such as allergic reaction and hyperactivity in human
(Khoo et al., 2019b). The carotenoids from microalgae also possess
some beneficial medical properties such as antioxidant activity that are
absent in synthetic colourants (Sathasivam and Ki, 2018).
Astaxanthin is a bright red secondary carotenoid, a ketocarotenoid
that is known as ‘super antioxidant’ because its antioxidant activity is
stronger than other carotenoids such as lutein, beta-carotene and can-
thaxanthin (Khoo et al., 2019b). Astaxanthin possess singlet molecular
oxygen-quenching activity, which prevents the ultraviolet radiation,
inhibits lipid peroxidation, and scavenges free radicals (Gwaltney-
Brant, 2016) as well as exhibits anti-inflammatory and anti-apoptotic
properties (Kamalanathan and Quigg, 2019). Astaxanthin is a pro-
mising carotenoid that has achieved a profit of $200 million per year
with the price around $2500 per kg (Hu, 2019). The main microalgal
producers of astaxanthin are H. pluvialis, C. zofingiensis, C. nivalis, B.
braunii, C. vulgaris, C. striolata, Monoraphidium sp., Chlamydocapsa sp.,
Neospongiococcum sp., Chlorococcum sp. and S. obliqus (Khoo et al.,
2019a). Most common researches reported that the accumulated as-
taxanthin in H. pluvialis can reach up to 3.8–5.0% (w/w), which de-
pends on its cultivation condition (Khoo et al., 2019a). Algatechnolo-
gies Ltd., AstaReal Inc., Beijing Gingko Group (BGG), Cyanotech
Corporation and Parry’s Pharmaceuticals are the major commercial
producers of Haematococcus astaxanthin supplements (Dufosse, 2008).
Beta-carotene (β-carotene) produced naturally from D. salina can
fetch a market price ranged from $300–$500/kg. At the same time, its
market is forecast to reach $532 million in 2019 (Velea et al., 2017). β-
carotene is the precursor of vitamin A or also known as retinol at which
the human body converts the β-carotene into vitamin A that is essential
for pregnant women and children. It is found that β-carotene provides
various health benefits such as protect the cornea, anti-aging, anti-
cancer, immune modulation and prevent cardiovascular diseases
(Barkia et al., 2019). Vitamin A deficiency will result in immune im-
pairment, night blindness, xerophthalmia and blindness in children. In
conjunction with that, it is a major public health problem in low-in-
come countries which mostly affect young children and pregnant
women. Besides, β-carotene is also used as animal feed additives and
D.Y.Y. Tang, et al.
colourant for food and beverage that confer yellow-to-orange colour
(Hu, 2019). The major microalgae species that produce β-carotene are
D. salina, D. tertiolecta, D. bardawil, B. braunii, C. nivalis, C. acidophila,
Chlorococcum sp., Chlamydocapsa sp., Tetraselmis sp., C. sorokiniana, P.
obovate and C. striolata (Sathasivam et al., 2017).
Microalgae also produce lutein that provides excellent antioxidative
properties to prevent or delay the onset of chronic diseases as well as
the treatment of cataracts, an eye disease that cause blurry or double
vision, faded colours and trouble seeing at night (Sun et al., 2015).
Lutein is produced by Chlorella sp., B. braunii, D. tertiolecta, C. nivalis, S.
almeriensis, P. urceolata, C. proboscideum, C. acidophila, N. gelatinosum,
Chlamydocapsa sp., Muriellopsis sp., Pyramimonas sp. and Tetraselmis sp.
(Sathasivam et al., 2017). The market price of lutein is approximately
around $910 to $15,000/kg with an estimated market of around $3.14
million in 2019 (Hu, 2019). The study by Del Campo et al. (2004)
showed that amount of lutein produced by Chlorella sp. was less than
astaxanthin, causing its market price is higher than astaxanthin.
2.2. Lipids
Microalgae have great potential in producing high amount of lipids
consisting of non-polar lipids (i.e., triacylglycerols molecules), polar
lipids or structural lipids (i.e., monounsaturated fatty acids (MUFA) and
polyunsaturated fatty acids (PUFA)), glycolipids or phytosterols and
waxes (Santos-Sanchez et al., 2016). Microalgae is well known for
producing high concentration of PUFA such as docosahexaenoic acid
(DHA), eicosapentaenoic acid (EPA), linoleic acid (LA), gamma-lino-
lenic acid (GLA) and arachidonic acid (AA) (de Morais et al., 2015).
PUFA produced by microalgae exhibits antioxidant, antibacterial, an-
tiviral, detoxifying capacities, prevents hypercholesterolemia, improves
brain function and proved to have good immune stimulatory effects (de
Morais et al., 2015; Roy and Pal, 2015). Food and Drug Administration
(FDA) has approved the use of DHA algal oil as an additive for infant
formula by Martek Biosciences. This DHA-rich algal oil is produced
from the microalgae, Schizochytrium sp. and Crypthecodinium cohnii. The
two main types of microalgal PUFA, DHA and EPA, are the primary
source of omega-3 fatty acids with the market price around $80 – 160/
kg and have the estimated market of $898.7 million at 2025 (Hu,
2019). In the past few years, marine fish was the main source of DHA
and EPA, however some of the issues had been arise such as not suitable
for the consumption by the vegan and the unpleasant smelly produced
from fish oil is not suitable to be used as a food ingredient. Moreover,
the leakage of fuel oil from the ships as well as the discharge of waste
chemicals comprised of mercury, dioxins, chlorinated pesticides and
polychlorinated biphenyls (PCB) from the factory have resulted in the
depletion of the world’s fish stock.
2.3. Polysaccharides
Polysaccharides are the essential products produced by the micro-
algae and the amount produced is varied among the species and genera.
Many literature studies have shown that the potential of microalgae as
polysaccharides producers were under investigation and had small or
limited market (Barkia et al., 2019). Polysaccharides obtained from the
microalgae can be used as metal ion chelators and protect against plant
pathogens (Michalak and Chojnacka, 2015). Algal polysaccharides
contain sulphate esters that are known as sulphated polysaccharides
and mainly produced by C. vulgaris and S. quadricauda. Sulphated
polysaccharides comprised of ulvan, carrageenan and fucoidan. Apart
from being widely used as food additives, carrageenan also demon-
strated antiviral and antioxidant activities (da Silva Vaz et al., 2016).
Recent work has showed that ulvan exhibited medicinal properties, for
example, anticancer, antihyperlipidemic, antifungal, hepatoprotective,
antiprotozoal, anti-inflammatory, antioxidant, anticoagulant, im-
munomodulation and enhanced skin tissue regeneration (Lekshmi and
Kurup, 2019).
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Bioresource Technology 304 (2020) 122997
2.4. Proteins and amino acid
Microalgae biomass are well known for its high protein composition
such as glycoprotein from C. vulgaris, C-phycocyanin from S. platensis
and phycoerthrin from P. cruentum (Sathasivam et al., 2017). Besides,
microalgae such as C. sorokiniana, C. minutissima, C. luteoviridis, C.
sphaerica, A. spiralis, C. nivalis, Aphanizomenon flos-aquae, Scenedesmus
sp. and Stichococcus sp. produce mycosporine-like amino acids that are
the strong ultraviolet (UV) absorbing compounds in nature
(Orfanoudaki et al., 2019; Sathasivam et al., 2017). Microalgae have
also been reported to have great capacity to synthesize enzymes for
different industrial applications such as phytases, α-galactosidase,
protease, laccases, lipase, cellulases, amylolytic enzymes, antioxidant
enzymes and carbonic anhydrase (Brasil et al., 2017).
Phycobiliproteins, a group of light-harvesting protein-pigment
complexes that comprised of C-phycocyanin, allophycocyanin and
phycoerythrin (Eriksen, 2008). Due to the features of highly fluor-
escent, phycobiliproteins are used as fluorescent promising labelling
reagents that can be employed in flow cytometry, fluorescence im-
munoassay, immunohistochemistry and other biomedical science ac-
tivities (Chew et al., 2017; Manirafasha et al., 2016). Spirulina platensis
are an excellent source of phycobiliproteins, particularly c-phyco-
cyanin, a natural blue pigment (Chew et al., 2019). These compounds
have been commercialised as the natural colourants in food industry
and nutraceutical products, such as use of phycocyanin from Spirulina
as colouring agent in soda ice cream and soda pop. The global market
was valued at $60 million in 2019 with Algapharma BiotechCorp, Co-
lumbia Bioscience and QuantaPhy. Inc are the manufacturers and
suppliers of phycobiliproteins (Hu, 2019).
3. Potential of microalgae for the production of high-value
compounds
Microalgae biomass offers many benefits by utilising the bioactive
compounds to generate promising and sustainable source of biofuels
and bioproducts. Under favourable growing conditions, microalgae are
able to divide their cells within 3 to 4 h (Williams and Laurens, 2010).
This fast reproduction ability allows the production of biomass within
3.5 h during exponential growth (Ngoc et al., 2015), allowing the
biocompounds to be accumulated in a short period of time. The com-
pounds associated with microalgae are generally recognized as safe and
environmentally friendly which are beneficial and harmless for direct
human consumption (Jha et al., 2017).
Microalgae cultivation does not have any significant negative im-
pact on food security or food chains as the cultivation process does not
interfere with the use of arable or fertile land that are used for con-
ventional agriculture (Manirafasha et al., 2016). This is because mi-
croalgae are able to survive in harsh environmental conditions for long-
term, such as wastewater environment, salt water, ice or hot springs
(Brennan and Owende, 2010; Rajkumar and Takriff, 2016; Tan et al.,
2018). Furthermore, microalgae can tolerate a broad range of pH,
salinity, temperature and contaminants. Consequently, microalgae are
able to grow in the environments that contain excessive CO2, sulphur
oxide and nitrogen oxide (Chew et al., 2017).
Moreover, microalgae have low demands for nutritional and spatial
cultivation requirements. The cultivation of microalgae requires small
supply of nutrients such as light, carbon sources, CO2, nitrogen, phos-
phorus and potassium (Manirafasha et al., 2016) without the use of
fertilizers like pesticides or herbicides. The manipulation of the culti-
vation conditions offers the possibility to enhance or induce the pro-
duction and accumulation of compounds in the microalgae (Morone
et al., 2019). Furthermore, microalgae helps to reduce the greenhouse
effect and global warming due to the assimilation of CO2 as a carbon
source in the cultivation process which reduces the release of excess
CO2 to the environment.
D.Y.Y. Tang, et al.
Table 1
. Advantages and disadvantages of cultivation systems.
System Advantages
Open system • Easily scaled up
• Cost effective (Low construction, maintenance and operating costs)
• Large culture areas and allowed for mass cultivation of biomass
Closed system ▪ Equal distribution of sunlight (artificial light on LEDs) over a large surface
area
▪ Do not lose water and CO2 by gas stripping
▪ Low or no risk of contamination
▪ Greater control of growth parameter of the cultivation conditions such as
pH, temperature, light and CO2 concentration
3.1. Cultivation of microalgae
The cultivation of microalgae is the preliminary step in the pro-
duction of bioactive compounds. There are three types of cultivation
techniques (i.e., batch, fed-batch and continuous culture). Batch culti-
vation is the system at which the microalgae are cultivated in a closed
container or environment with fixed parameter and no addition of fresh
nutrients during the cultivation. This results in the reduction of the
amounts of nutrients over time (Lim and Shin, 2013). This cultivation
technique is the easiest method however this closed system will cause
self-shading effect of microalgal cell and inconsistent irradiance due to
the continuous consumption of nutrients (Zhu, 2015). Contrarily, fed-
batch or semi-continuous culture continually supplies microalgae with
nutrients and the discharge of the effluents or waste products at the
same time in order to sustain the concentration of culture medium in
the system (Tan et al., 2018), making it more efficient and reliable than
batch cultivation. However, the drawbacks of this system involves the
difficulty in controlling and monitoring the occurrence of contamina-
tion and deviations in the microalgal growth pattern if the feed is ap-
plied on a fixed system without feedback control (Tan et al., 2018).
Continuous cultivation is similar with batch cultivation with slight
modification where the introduction of new medium or nutrients is
added until the microalgae reaches an exponential growth phase. This
allows the microalgae to reproduce continuously at an intermediate
rate and the growth pattern follows the normal growth cycle. This
culture technique has high product yield or production rate over the
extended period and easy manipulation of the nutrient concentration
and pH (Hoskisson and Hobbs, 2005). Hence, this makes continuous
cultivation more preferred as compared to batch and semi-continuous
cultivation conditions in the current scenario. However, this culture
technique is not favoured in the industrial scale due to high risk of
contamination as well as the difficulty and complexity of the process
(Egli, 2015).
Photoautotrophic, heterotrophic, mixotrophic and photo-
heterotrophic are the main microalgae cultivation modes. The most
common cultivation modes are photoautotrophic and heterotrophic
cultivation modes (Chew et al., 2018).
• Photoautotrophic cultivation: Utilises CO 2 as the sole carbon source
and light
• Heterotrophic cultivation: Uses organic carbon, such as sugars,
wastewater, acetate, and organic acids as a source of energy and
carbon in the absence of solar or light.
• Mixotrophic cultivation: CO2 and organic compounds are fed to the
microalgae and both the respiratory and photosynthetic metabo-
lisms occur concomitantly.
• Photoheterotrophic cultivation: Light and organic compounds act as
a source of carbon.
There are two types of systems available for microalgae cultivation,
4
Bioresource Technology 304 (2020) 122997
Disadvantages
• Difficult to control the culture condition
• Low biomass productivity (poor mixing)
• Susceptible to contamination by microorganisms
• Affect by climate changes, excessive evaporation of water and inconsistent
light source
•▪ High
Lower layers may suffer from insufficient CO and limited amount of light
2
investment cost (operating and capital costs)
▪ Adhesion of microalgae on plastic or glass surface cause the blockage of the
pipes
which are open system and closed system. The examples of open system
are open pond and raceway pond. Open ponds are generally designed as
a paddlewheel-driven raceway ponds with the depth of 0.2 m–0.5 m for
the flow of nutrients and water along with microalgae to ensure con-
stant exposure to the environment and maintain the pond integrity. The
operation of artificial ponds is continuous with the constant addition of
CO2 and nutrients to keep the system balanced. At the same time, mi-
croalgae are expelled from the tank at the opposite end. For optimal
performance, it is recommended to culture the microalgae in a pond
with maximum volume of 30 m3 (Santos-Sanchez et al., 2016).
On the contrary, the closed systems, which is also known as pho-
tobioreactors, is a reactor that uses light energy to conduct a photo-
biological reaction and is typically used to produce large quantities of
microalgae biomass under controlled conditions (Chisti, 2007; Mata
et al., 2010). The photobioreactor is made up of plastic or glass that
designed as three configurations, which are spiral tubes, flat panels and
bubbles column (Santos-Sanchez et al., 2016). From an economic point
of view, relative to open raceway ponds, a closed photobioreactor is
very expensive due to high capital cost, for instance, the production
cost of the microalgae cultivation system can range from 5€/kg (5.56
US dollars/kg) for open raceway and 50€/kg (55.45 US dollars/kg) for
tubular photobioreactor (Fernández et al., 2019). Hence, due to the
high biomass production cost, Agnes Janoska and his team had created
a novel concept of cultivating microalgae that was liquid form-bed
photobioreactor to reduce harvesting costs and energy requirements
(Janoska et al., 2018a; Janoska et al., 2018b; Janoska et al., 2017). It
was an alternative concept as compared to the existing liquid-phase
photobioreactors and operated based on the basis of exposure of a large
volume of foam to illumination and continuous gas supply to the
shallow layer of culture at the bottom of the reactor (Janoska et al.,
2017). In short, closed cultivation system is the most appropriate
system to cultivate microalgae since the culture conditions can be
controlled but is limited by the high production cost and production of
smaller quantity of biomass. Table 1 has summarized the advantages
and disadvantages of open system and closed system.
3.2. Harvesting process
Microalgae harvesting methods involve the process of isolation or
removal of microalgae biomass from the growth medium and can be
divided into chemical, physical, electrical or biological methods. The
common methods applied for harvesting of microalgae include sedi-
mentation, flotation, coagulation and flocculation, centrifugation,
electrophoresis and filtration as summarised in Table 2 (Show et al.,
2020; Singh and Patidar, 2018; Tan et al., 2018). To ensure an effective
harvesting efficiency from microalgae, there are a few criteria in de-
ciding which of the harvesting technique is suitable to remove the
culture medium from microalgae biomass, such as low production cost,
large biomass quantity at mass scale, good quality of harvested com-
pounds, short processing time, species dependent and contaminant-free.
D.Y.Y. Tang, et al. Bioresource Technology 304 (2020) 122997

Table 2
Comparison studies between different harvesting techniques.
Harvesting techniques Advantages Disadvantages

Filtration (Membrane process) • High recovery efficiency • Time consuming

• No usage of power or electricity • Occurrence of membrane clogging
• Low shear stress • High cost and require regular replacement of membrane
• Affected by hydrodynamic conditions and membrane size
Chemical coagulation and flocculation • Fast • High cost
• Easy to be applied • Difficult to separate the coagulant from harvested biomass
• Less cell damage
• Less power or energy usage
Electrocoagulation • Fast • High costs (equipment and operational cost)
• Easy to be applied • Metal contamination
• No chemicals required
Bio-flocculation • Fast • Possibility of mineral or microbial contamination
• Easy to be applied • Difficult to separate the coagulant from harvested biomass
• No need energy supply and chemical usage
Flotation • Low cost • Needs surfactants
• Low demand for space • High cost and metal contamination (electroflotation)
• Suitable for large scale
• Short operation time
Gravity sedimentation • Low cost • Long operation time
• Not suitable for low density cells
Centrifugation • High recovery rate (achieve up to 95%) • High operation and maintenance costs
• Low risk of contamination • Expensive if applied in large scale

Ozonation-dispersed flotation (ODF)

• Fast and effective
Fast
Drying • Low cost
In short, despite a wide range of harvesting methods, there is no single
technique proved to be effective in harvesting microalgae biomass in
terms of cost and recovery rate (Singh and Patidar, 2018). The har-
vesting method can put up the total production cost by 20–30%.
Therefore, to achieve the desired liquid–solid separation or biomass
recovery rate in a pilot scale, a suitable harvesting method that com-
prise of one or more of the combination of methods is needed (Mata
et al., 2010).
4. Potential of microalgae in enhancement the quality of natural
products
Natural products are characterized as the products of natural origins
including an entire or part of an organism that has not undergone any
processing or treatment other than a simple preservation process such
as animals, plants or microorganisms (Gurnar, 1999). It is feasible to
incorporate high-value bioactive compounds from microalgae biomass
into majority of the products that are consumed on a regular basis to
increase its nutritional and functional value.
4.1. Pharmaceutical industry
Microalgae have drawn great deal of interest in recent years despite
their potential therapeutic applications. Various research studies have
shown that the bioactive compounds from microalgae biomass de-
monstrated medicinal properties such as antimicrobial, antiviral, anti-
fungal, anti-tumour, neuroprotective activities that have been attrib-
uted to the pharmaceutical industries (Barkia et al., 2019; Jabeen et al.,
2019; Najdenski et al., 2013; Singab et al., 2018). Table 3 have sum-
marised the pharmacologic activities of different types of microalgae.
Microalgae also synthesize compounds that are used for the targeted
delivery of anticancer drugs, particularly poorly water-soluble drugs.
The diatomaceous earth microparticles extracted from marine micro-
algae are used for targeted therapies for cancer, for example, colorectal
cancer. The compounds were first coated with vitamin B12, a tumour
targeting agent, and then filled with anticancer agent, cisplatnum or
cisplatin for the efficient delivery of the cancer drug to the targeted site
and to kill the cancer cells (Delasoie et al., 2018). Furthermore, some of
• Risk of cell destruction
Expensive
• Drying rate depends on climate or weather
• Inconsistent sunlight
• Risk of compounds loss
the microalgae strains (e.g., Chlorella sp., Scedesmus sp., Chlamydomonas
sp., Nannochloropsis sp., Tetraselmis sp., Botryococcus braunii) were also
used for the evaluation for their potential use as photosensitizers in
photodynamic therapy or in other words, light-associated treatment of
tumours. The study by Jabeen et al. (2019) showed that these micro-
algae constituents significantly reduced the proliferation and showed
the photo-damage effects on the four cancer cell lines, which were
human lung carcinoma, human breast adenocarcinoma, human prostate
cells derived from metastatic site lymph node and human breast ade-
nocarcinoma. Therefore, these microalgae strains were suggested as the
potential photosensitizers but further research, such as in vivo and in
vitro experiments, is needed to confirm their efficacy.
The high value compounds produced by the microalgae demon-
strated different therapeutic potential that can be integrated in the
production of new drugs to eradicate the diseases, especially incurable
diseases or infections. Some examples of companies that have derived
pharmaceutical products from algae are Agri Life SOM Phytopharma
(India) Limited, Piramal Healthcare, Rincon Pharmaceuticals and Novo
Nordisk India Private Ltd. In future, microalgae extracts can be used to
develop vaccine to provide immunity to diseases or infections such as
influenza virus and Zika virus that are the biggest and serious health
threats to the people worldwide.
4.2. Cosmetics and personal care
Microalgae generate compounds that offer a potentially infinite
diversity of benefits for the skin including promoting blood circulation,
moisturising the skin, activating the cell renewal and the metabolism,
increasing the skin's resistance and having an anti-inflammatory effect
on the skin. The cosmetics and personal care products include oral care,
skin care, sun care, hair care, decorative cosmetics, body care and
perfume. Skin care products range from facial cleanser, toner, scrub,
essence, moisturizer to mask with different functions such as hydration,
brightening, pore-tightening and anti-aging to restore, protect and re-
generate the skin. Discussions about the skin care products derived
from microalgae biomass as summarised in Table 4.
Daniel Jouvance is a company that uses microalgae to formulate all
or part of their product lines including face care, body care and

5
D.Y.Y. Tang, et al. Bioresource Technology 304 (2020) 122997

Table 3
Evaluation of pharmacologic activities from microalgae.
Microalgae Pharmacologic activity Refs.

N. laevis, S. platensis, C. vulgaris Production of aqueous protein extracts and hydrolysates that exhibit antioxidant (Alzahrani, 2018)
properties, inhibit activity of angiotensin I-converting enzyme and acetylcholinesterase
C. vulgaris B. Inhibit growth of Staphylococcus epidermidis and prevent foot odour (Suhara et al., 2019)
Platymonas sp. Synthesize silver nanoparticles that have antibacterial activity against the pathogens (Elangovan et al., 2019)
such as Vibrio alginolyticus, Bacillus flexus and Streptococcus sp.
S. limacinum, N. texensis, G. sulphuraria, E. carotinosa, S. Shown antioxidant, anticancer and cytotoxic effects against human hepatocellular liver (Gürlek et al.,2019)
bacillaris, C. cohnii carcinoma cells (HepG2)
C. vulgaris Control the infectious disease by Pseudomonas aeruginosa and Staphylococcus aureus (Gayatri et al., 2019)
through inhibition of biofilm formation
Accelerate wound healing and showed anti-bacterial and anti-inflammatory properties (de Melo et al., 2019)
Neochloris aquatica RDS02 Shown the effects of antibacterial (Klebsiella pneumoniae, Escherichia coli, Staphylococcus (Selvan et al., 2018)
aureus, Bacillus subtilis), cytotoxic (cancerous HeLa cells) and antiviral (Herpes simplex
virus 1 and 2) with silver nanoparticles (Ag NPs) produced
I. galbana, D. tertiolecta, T. suecica, N. oculata Antibacterial activity against fish pathogenic bacteria, Vibrio alginolyticus (Kanaan, 2019)
I. galbana, D. salina, P. lutheri, T. gracilis, T. trahele, T. Demonstrated activities of antimicrobial (Staphylococcus aureus, Klebsiella pneumoniae, (Peraman & Nachimuthu,
sp., Navicula sp., C. calcitrans, D. inornata Pseudomonas aeruginosa, Bacillus subtilis); antifungal (Aspergillus brasiliensis, Aspergillus 2019)
fumigatus, Candida albicans); anthelmintic (Indian earthworms, Pheretima posthuma)
T. erythraeum Development of silver nanoparticles that showed antibacterial activity against bacterial (Sathishkumar et al., 2019)
strains (P. mirabilis, S. aureus) as well as drug resistant strains (S. pneumoniae, E. coli, S.
aureus)
T. suecica Produce antimicrobial peptides (AMPs) that show bactericidal effects against gram- (Guzmán et al., 2019)
negative and gram-positive bacteria (P. aeruginosa, B. cereus, E. coli, S. typhimurium, S.
aureus, L. monocytogenes, M. luteus)
Spirulina platensis Antioxidant and antiproliferative against human hepatocellular carcinoma cells (HEPG2) (Zaid et al., 2015)
and colon carcinoma cells (HCT116)
Antiviral activity against foot and mouth disease virus (FMDV) Types O, A and SAT2 (Daoud & Soliman, 2015)
Antimicrobial activity against Candida albicans and Escherichia coli (Pratita et al., 2019)
Chlorella pyrenoidosa, Scenedesmus sp., Chlorococcum sp. Produce exopolysaccharides that has antioxidant and inhibit the proliferation of human (Zhang et al., 2019)
colon cancer cell lines
Chlorella sorokiniana, Scenedesmus sp. Antitumor activity against murine L5178Y-R lymphoma cell lines (Reyna-Martinez et al.,
2018)
Botryococcus braunii Anticancer properties by photosystem I Light-Harvesting Complex I (PSI-LHCI) (Ovalle et al., 2018)
Tribonema sp. Produce sulphated polysaccharides that act as immunostimulant and show anticancer (Chen et al., 2019)
activity (RAW264.7 macrophage cells and HepG2 cells)
Botryidiopsidaceae sp. Exhibit antioxidant and anticancer activities against cervical cancer cells) (Suh et al., 2017)
Nannochloropsis salina Antimicrobial and anticancer activities against human MCF-7 cancer cell line (human (Sayegh et al., 2016)
breast cancer)
S. platensis, S. obliquus, D. salina Shown antiviral (HCV genotype 4a replicon, coxsackievirus B4, rotavirus, HSV type 1), (Singab et al., 2018)
antitumor, antioxidant and anticholinesterase activities
Leptolyngbya sp., Chlorellaceae, Scenedesmus sp., Anti-influenza activity (Silva et al., 2018)
Staurastrum sp.
Schizochytrium sp. Vaccine candidate against Zika virus (Márquez-Escobar et al.,
2018)
Coccomyxa sp. KJ Anti-herples simplex virus activity (Hayashi et al., 2019)
Spirulina maxima Produce extracellular L-asparaginase that had antiviral (Coxsackie B3) and (Abd & El, 2019)
antiproliferative activities (lung carcinoma, hepatocellular carcinoma, prostate
carcinoma cell lines)
Synechocystis sp., Gyrodinium, Impudium Antiviral activity against influenza virus (Kim et al., 2012)
S. plantensis, C. vulgaris, N. ocaenia, Picochlorum sp., H. Neuroprotective potential against Alzheimer's disease (Olasehinde et al., 2017)
crinita, C. volubile, B. braunii, T. chuii
Dunaliella tertiolecta Produce the pigment, violaxanthin, that has antineoplastic effects (Abida et al., 2013)
Chlorella pyrenoidosa Produce C. pyreniodosa antitumor polypeptide (CPAP) that inhibit the activity of human (Wang & Zhang, 2013)
liver cancer cell

Table 4
Properties of microalgae for application in skin care products.
Microalgae Function Refs.

Monodus sp., Thalassiosira sp., Chaetoceros sp., and Integrated into anti-aging products for collagen stimulation (Zanella et al., 2019)
Chlorococcum
Phaeodactylum tricornutum Improve skin elasticity and firmness as well as to protect the skin against UV (Ariede et al., 2017)
exposure
Chlamydocapsa sp. (snow algae) Hydrating the skin and increase the longevity of the skin following exposure to (Ariede et al., 2017)
dryness, UV radiation or cold
Spirulina platensis Avoid the harmful activity in the dermis and epidermis by radicals (Raposo et al., 2013)
Porphyridium sp. (red microalgae) Antioxidant activity against linoleic acid autoxidation and replace hyaluronic (de Jesus Raposo et al., 2015)
acid as a biolubricant
Chlorella vulgaris and Spirulina maxima Produce vitamins that help to get rid of dark circles, refresh and purify the skin (Joshi et al., 2018)
Aurantiochytrium sp., Thraustochytrium sp. and Produce squalene that used in moisturizing lotions to provide ideal skin (Kaya et al., 2011; Patinier, 2014;
Schizochytrium sp. properties by stimulating emollient and antistatic actions Pora et al., 2014)

6
D.Y.Y. Tang, et al.
personal care for over 30 years. For example, Algo[2]IODe by Daniel
Jouvance contains a high concentration of marine iodine from
Thalassiosira to help delay the appearance of new fatty cells and this
gives a sliming cure effect for 7 days. Dunaliella salina microalgae which
rich in marine glycerine had been exploited in AQUACÉANE series and
is a powerful moisturizing agent that provides lasting hydration to skin.
ÉCLACÉANE by Noctiluca microalgae that emit visible and shimmering
light on the surface of the ocean, offers the skin a new source of ra-
diance. Furthermore, some of the microalgal derived cosmetics pro-
ducts have been commercialized. For instance, PEPHA®-TIGHT is a
pure, unique natural skin firming and highly purified biotechnologi-
cally produced extract from N. oculate microalgae and was patented to
be used in anti-aging creams (Sumathy and Kim, 2011). Subitec, a
German technology company, had utilised the snow algae (C. signiensis)
as the anti-aging cosmetic ingredient. This high value biotechnological
product, the “Snow Algae Powder”, was successfully introduced to the
market in 2014. The snow algae extracts are effective in reducing the
loss in collagen expression in aged fibroblasts, significantly enhanced
skin hydration and smoothed crow's feet wrinkles. Besides, ESTÉE
LAUDER also launched a microalgal-based product, named Nutritious
Microalgae Pore Minimizing Shake Tonic, formulated with a nutrient-
dense microalgae blend of Chlorella, Spirulina and Laminaria saccharina
to purify and balance the skin. Sun Chlorella skin cream from Japan is
the first skin-nourishing cream that use Chlorella to hydrate and nourish
the skin. The extracts produced by microalgae also used in producing
mask in rejuvenating, moisturising and renewing the skin. For example,
B.liv nano bio-cellulose mask is made from Organic Spirulina, a blue-
green algae from deep sea to hydrate, repair and clarify skin as well as
to protect skin from the free radical damage. Besides, pure face mask
from L’Oreal Paris is made from combination of clay and red algae to
exfoliate, cleanse and refine the skin. The superfood skin reset anti-
oxidant mask from Youth To The People is a rejuvenating cream mask
enriched with Seagreens Spirulina, bioactive microalgae and other
compounds to restore and rejuvenate skin.
Sunscreen is a topical product that protect us against ultraviolet
(UV) light and against sunburn. The extracts of Spirulina sp. and
Chlorella sp. are used as ingredients of sun block (Jha et al., 2017).
Chlorogloeopsis sp. extract protects the keratinous tissue by preventing
damage from long wave ultraviolet A (UVA) and short wave ultraviolet
B (UVB) and thus preventing photo aging, wrinkles formation and skin
sagging (Ariede et al., 2017). Isochrysis sp. extracts are also applied in
sunscreen formulation that contain organic and inorganic filters with
SPF 15 to prevent the transmission of ultraviolet (UV). Lastly, Nanno-
chloropsis sp. has shown effective measure against transmission of UVA
and UVB (Ariede et al., 2017).
Apart from that, good and beautiful hair gives better impression, so
proper hair care is essentially important. Chlorella vulgaris and Spirulina
maxima microalgae treat the dandruff for stimulation of hair growth
(Joshi et al., 2018). Extracts of Thalassiosira sp., Monodus sp., Chlor-
ococcum sp. and Chaetoceros sp. are suggested for the formulations that
deal with hair loss (Zanella et al., 2019). These microalgae extracts
regulate the melanogenesis in skin and hair, proliferation of melano-
cytes, differentiation of keratinocytes and the growth of hair follicles
(Zanella et al., 2019). Oil produced by Chlorella sp. demonstrated the
ability to make the skin and hair soft and more flexible (Brooks and
Franklin, 2013). A study by Herrmann et al. (2012) discovered that the
methanol extract (BIO1631) of the marine water microalgae Isochrysis
sp. is highly effective in increasing the percentage of hair follicles in the
anagen phase by reducing apoptosis of hair follicle cells in the bulb
region. The extract exhibited an average increase in hair shaft elonga-
tion, thus is a highly promising candidate for preventing hair loss.
However, due to the toxicity of methanol extract, the extracted bioac-
tive product is unreliable for consumption in human body. Other
commercial products such as Dove Regenerative Repair Shampoo re-
stores the hair strength by providing nourishment and repair the da-
maged hair.
7
Bioresource Technology 304 (2020) 122997
The microalgal extract also can be used in decorative cosmetics
products such as foundation, concealer, lipstick and eyeliners. For ex-
ample, Skinicer ocean kiss lipstick is a hygienic lipstick that contains
the combination of natural hydrating ingredients and microalgae ex-
tract, Spiralin. It is clinically proven to have antiviral, antifungal, an-
tibacterial, collagen-forming, cell-regenerative, as well as UV-protective
properties. Phycocyanobilin and phycoerythrobilin produced from
Spirulina sp. and Porphyridium sp. act as pigments for eye-liner and
lipsticks (Hamed, 2016).
Nowadays, hair colouring or hair dyeing is the popular and common
practice for youths’ generation. However, the chemicals present in
synthetic hair dye can cause severe damage to hair such as hair fall, hair
thinning and easy breakage. Synthetic hair dye may cause allergic re-
action in some people and there had news reported that synthetic hair
dye may increase the risk of developing cancer. Microalgae extracts
were shown to produce carotenoids or pigments naturally (Khoo et al.,
2019a; Sathasivam and Ki, 2018) and thus can be exploited to produce
hair colourant or hair dye because the microalgae-based products are
regarded as safe as compared to synthetic hair dye.
4.3. Food industry
In United States, Food and Drug Administration (FDA) recognizes
the algae-based products or additives as safe (Wijnands et al., 2008).
Cookies, biscuits, pasta and dairy products are some of the examples of
microalgae-based food ingredients (Caporgno and Mathys, 2018). Dairy
products can be incorporated with bioactive compounds from micro-
algae for health benefits. For example, Arthrospira sp. in fermented milk
and yogurts can promote the growth and increase the viability of de-
sired probiotics (Varga et al., 2002). Apart from incorporation of
Chlorella sp. into yogurts, it has also been added into cheese to increase
the hardness and springiness and at the same time, reduce the melt-
ability and cohesiveness (Cho et al., 2004; Jeon, 2006). Phycocyanin
extracts from Arthrospira platensis have been introduced in the baking of
cookies to increase fibre and protein content (Singh et al., 2015). The
incorporation of H. pluvialis into the cookies aids in decreasing the
glycaemic response and at the same time increase the antioxidant ca-
pacity (Hossain et al., 2017). Batista et al. (2017) improved the nutri-
tional and potential health benefits by incorporating C. vulgaris, T.
suecica, A. platensis and P. tricornutum inside cookies to boost the pro-
tein and antioxidants contents.
Pigments and carotenoids from microalgae can be used as food
additives as colourings and thickeners (Mourelle et al., 2017). Car-
otenoids produced from Dunaliella sp., Chlamydomonas sp., Chlorella sp.,
Cyanidioschyzon sp., Synechocystis sp. and S. platensis act as food col-
ourant (Chu, 2012). Arthrospira sp. was also used as the ingredient for
extruded snack food for the purpose of enrichment (Lucas et al., 2018).
These microalgae can be used as a protein ingredient in drinks, for
example Spirulina platensis in drinks for sport nutrition as Spirulina
platensis proteins contain all amino acids needed and to increase the
athletes’ endurance and performance (Gubanenko et al., 2019).
Moreover, pasta is a popular dish in the diet in European and Asian
people. Incorporation of microalgae will not affect the cooking and
textures of pasta (Fradique et al., 2010) and high microalgae con-
centration in pasta will improve stickiness and maintain its elasticity
(Caporgno and Mathys, 2018). To enhance the nutritional content of
fresh spaghetti, C. vulgaris and A. maxima can be added (Fradique et al.,
2010). Adding D. vlkianum and I. galbana into pasta provides ω-3 PUFAs
and antioxidants with potential health benefits (De Marco et al., 2014;
Fradique et al., 2013; Gouveia et al., 2008). The ability to produce li-
pids (fatty acids) by microalgae such as I. galbana, P. tricornutum, C.
calcitrans, M. subterraneus, S. obliquus, N. gaditana, C. cohnii and T.
pseudonana is another highly interesting aspect in the food industry
(Klok et al., 2014). The microalgae oil produced have similar compo-
sition to vegetable oils and are rich in high-value PUFA such as EPA and
DHA. The fatty acids produced can be utilised as nutritional supplement
D.Y.Y. Tang, et al.
in tablets, capsules, or powders form or for use in nutraceuticals (García
et al., 2017). Microalgae oils that are rich in docosahexaenoic acid
(DHA) from Schizochytrium sp. have been formulated in the infant
products, since it is comparable with other traditional sources of DHA.
The study by Ben Atitallah et al. (2019) demonstrated that addition
of Isochrysis galbana, Chlorella minutissima and Picochlorum sp. into
canned fish burgers improved the texture, sensory acceptability, nu-
tritional content and functional properties (water and oil holding ca-
pacities) as compared to the rest of the formulations. The incorporation
also ameliorated the antioxidant activities of the microalgae-supple-
mented fish burgers. The possible uses of the polysaccharides from
microalgae as a prebiotic, source of fibre is another nutritional aspect of
interest though these are yet to be developed (Raposo et al., 2013).
There are some examples of the commercial products that utilise
microalgae in the production of food. For instance, the chocolate pro-
ducts, M&M's use Spirulina as a natural colouring. Some cooking oil
companies use microalgae technology to produce healthy cooking oils
for example, Thrive® Algal Oil (Chlorella) and Naturel Forte DHA
cooking oil by Lam Soon Sdn.Bhd, Malaysia. Lee Biscuits, Malaysia also
uses Spirulina in the production of crackers. Chlorella and Spirulina are
used in the production of beverage (cereal drinks) to increase the nu-
tritional value in products like Gold Choice 3 in 1 Chlorella Cereal
Drinks, Nature’s Own® Instant Brown Rice Cereal with Spirulina, AIK
CHEONG Vita Flakes Matcha Spirulina, Super Nutremill 5in1 Spirulina
with Oat and Tesco Choice 3 in 1 Spirulina Pre-Mixed Cereal Drink.
However, some properties of microalgae have limited their appli-
cation in food products. For example, the antioxidant activity of
Chlorella sp. and Arthrospira sp. can cause the colour and flavour
changes in foods and these changes are typically regarded by consumers
as undesirable (Beheshtipour et al., 2013). Next, the microalgae, for
instance Chlorella sp. and Spirulina sp. that confer green colour have
restricted their use as colourings in daily-use products because it will
adversely influence consumers’ perception of the taste and quality.
Furthermore, some products have a slight fishy flavour when micro-
algae are added and may be deemed unfavourable by the consumers
(Fradique et al., 2013).
4.4. Transportation
The gradual depletion of fossil fuels and the increased emissions of
greenhouse gas in large cities have urged the generation of renewable
energy to resolve the problems such as environmental pollution and the
global depletion of fossil fuels like natural gas and petroleum (Cruz
et al., 2018). Therefore, researchers are currently in the progress of
developing biofuels from microalgae, a renewable energy thatis derived
from different origins such as animals and plants (e.g., soybean, sun-
flower, palm oil, coconut). The oil yields and growth rates vary con-
siderably between different oilseed crops (Chisti, 2007; Hu et al., 2008),
while microalgae are able to synthesize rapidly and accumulate large
amount of lipids up to 85% (Goh et al., 2019; Gupta et al., 2019).
Microalgae are capable of synthesizing 58,700 L oil per hectare that can
produce 121,104 L biodiesel per hectare of land, a transition that is
promising over conventional fossil fuels and the global scientific com-
munity pay special attention to microalgae in the production of biofuels
as an alternative sustainable energy (Chisti, 2007; Mata et al., 2010).
Recent decades have seen the transformation of microalgae biomass
into various forms of biofuel such as biodiesel, bioethanol, biohy-
drogen, and bio-oil that potentially address the current energy crisis
(Suparmaniam et al., 2019). The lipids formed by microalgae contain
twice the energy provided by carbohydrates, meaning that the fuel
energy content will experience a two-fold increase outstripping other
terrestrial plants for the production of biofuel (Rawat et al., 2013).
Microalgae are seen as an ideal feedstock for biofuels due to their ad-
vantages, such as their phototropic features, fast growth rate, high
production of biomass and less water and land needed for growth.
Botryococcus braunii microalgae has the highest acummulated lipid with
8
Bioresource Technology 304 (2020) 122997
a dry weight of 43%, while the Tetraselmis suecica and Dunaliella ter-
tiolecta microalgae contains less than 10% (Kamalanathan and Quigg,
2019). Chlorella sp., particularly Chlorella vulgaris, is among the mi-
croalgae of great interest for biofuels because it can accumulate large
amounts of lipids, rapid growth rate and easy for cultivation (Liu et al.,
2008). More importantly, microalgae oil is more economical as com-
pared to the biomass from other oilseed crops and terrestrial plants.
Biodiesel derived from microalgae provides similar properties (e.g.,
density, fire point, viscosity, heat values) compared to petroleum diesel
(Ahmad et al., 2011). The biodiesel derived from microalgae also has
high energy density, and is cleaner as compared to petroleum-based
fuels (Tan et al., 2015). Due to the environmental impacts caused by
other feedstock, till now, there are no other potential resources of
biodiesel that are realistic and practical to replace the sustainability of
petroleum diesel alike microalgae.
In 2009, a research program was carried out by ExxonMobil and
Synthetic Genomics (SGI) in the development of advanced biofuels from
algae. This joint effort is working in the direction of the production of
10,000 barrels of algae biofuels by 2025. By adopting the cell en-
gineering technologies at SGI, the research team modified the algae
strain to raise the oil content from 20% to more than 40%. From there,
the team had discovered a new mechanism to increase the production
of oil by discovering a genetic change that could be fine-tuned to reg-
ulate the conversion of carbon to oil in the microalgae species,
Nannochloropsis gaditana.
In short, microalgae have the potential to produce renewable fuels
such as biodiesel, bioethanol, biohydrogen, methane and syngas
(Suparmaniam et al., 2019). Microalgae-based biofuels are biodegrad-
able, non-toxic, low emission of sulphur and high release of oxygen
(Khan et al., 2018).
5. Critical points in mass scale use of microalgae
The latest microalgae technology in terms of cultivation and har-
vesting is unable to produce the large amount of microalgae biomass,
which is approximately more than 100 kt/year at the production cost
below 1.0 €/kg for industrial purposes (Fernández et al., 2019). In other
words, the commercial use of microalgae biomass as a source of useful
products are still not economical due to a few issues and challenges
despite a lot of intensive research efforts on microalgae being made
(Caporgno and Mathys, 2018). The challenge is mostly on the upstream
and downstream processing of microalgae that will determine whether
the microalgae biomass can achieve the maximum production of high-
value compounds for the whole year production. As an example, the
changes in certain cultivation parameters, such as pH, light intensity,
nutrients, CO2 concentration, humidity and contamination by other
microorganisms, can affect the final biomass composition profile. Aside
from that, the various types of cultivation system still remain a chal-
lenge for the utilization of microalgae to produce useful compounds.
Low cost open system is preferred in industrial scale as compared to
high cost closed system that has high biomass productivity, but it is
susceptible to contamination. Moreover, the climatological conditions
and the conditions of harsh environment also affects the yield of mi-
croalgae biomass (Manirafasha et al., 2016).
Furthermore, the downstream processing of microalgae biomass, for
example, extraction, isolation and purification steps, is complex and of
high cost. The composition of carbohydrates, proteins, lipids, enzymes
and other compounds produced by microalgae biomass are different
among the species. The biocompounds produced may be fragile, low
quantity, lost or substantially altered during the extraction process,
making the process of analysis and industrial scale-up to be difficult.
Hence, it is a significant challenge for the identification, characteriza-
tion and extraction of a single effective compounds from microalgae
biomass.
The quality of the microalgal-based products is another considera-
tion to be evaluated. The research on the application of the properties
D.Y.Y. Tang, et al.
of microalgae compounds in the pharmaceutical areas, for instance,
antioxidative, antihypertensive, anti-tumour, neuroprotective and an-
ticoagulant functions, is limited and the potential health benefits are
not evident without the data from non-clinical trials and human clinical
trials (Caporgno and Mathys, 2018). In short, the high cost of cultiva-
tion, extraction and harvesting techniques as well as low yield restrict
the use of microalgae as a source of bioactive compounds production in
mass scale.
6. Future work and opportunities
To overcome the challenges faced by utilization of microalgae in
industrial scale, the microalgal cultivation and downstream processes,
needs to be optimized and improved for the high recovery and purity of
the compounds from various microalgal species. The investment of
resources in new or existing techniques and equipment in the future
microalgal-based research should put focus on the potential, cost and
maturity of the cultivation and harvesting techniques to increase the
growth rate and extraction of bioproducts from biomass (Show et al.,
2020). In other words, these novel techniques need to be practicable in
the industrial scale with low production cost and then lead to good
economic at large scale. The microalgae cultivation system should be
advance, particularly for the design of photobioreactors, for continuous
and mass production of biomass without occurrence of contamination.
In addition, a suitable novel microalgae cultivation mode should be
developed for large scale biomass production with the low probability
of occurrence of contamination by considering the growth and photo-
synthetic conditions of different microalgae species (Cruz et al., 2018;
Velea et al., 2017). Besides, microalgae are amendable to genetic en-
gineering, so this alteration can be applied to modify or improve the
genetic sequences of existing microalgae strains to enhance the pro-
duction of targeted metabolites from microalgae (Ben Atitallah et al.,
2019).
Furthermore, from the studies by Suparmaniam et al. (2019) and
Tan et al. (2018), it can be suggested that there is a need for develop-
ment of new extraction techniques or improvement of existing culti-
vation or harvesting techniques to increase the oil extraction rate from
the oil-producing microalgae in large scale as well as the discovery of
more strains with high yield of lipids. In addition, the parameters of the
culture conditions can be changed to induce the production of com-
pounds from microalgal biomass. The quality, safety and efficacy of
microalgal-based products for human consumption, such as drugs,
cosmetics products, personal care products, food and beverages, must
be carefully regulated to ensure they are 100% safe to be consumed
without causing any adverse effects to the consumers (Morone et al.,
2019; Singh et al., 2020). Therefore, the conduct of further clinical and
non-clinical research is essential to verify and confirm the efficacy,
bioavailability, safety, side effects, potential market and beneficial ef-
fects of the microalgal-based products for humans. Through the study
by Márquez-Escobar et al. (2018), Silva et al. (2018) and Daoud and
Soliman (2015), it is suggested to discover new microalgae strains or
deep intensive research on existing microalgae strains to reveal more
bioactive compounds that have potential in the development of new
drugs to treat incurable diseases and drug-resistant infections caused by
viruses, bacteria, parasites or fungi such as lupus, Alzheimer’s disease,
HIV/AIDS, polio, influenza, Zika virus, malaria and Ebola virus. To
summarise, more research should be conducted to improve the up- and
downstream processes to produce bioactive compounds from micro-
algal biomass and its conversion for commercialization in different in-
dustries in low cost.
7. Conclusions
This review investigated the potential of microalgae to be exploited
in different industries including pharmaceutical, food, personal care
and transportation. Various renewable and sustainable bioactive
9
Bioresource Technology 304 (2020) 122997
natural compounds with beneficial properties can be extracted from
microalgae biomass and incorporated into industrial products to re-
place the synthetic materials and save cost. However, to commercialize
microalgae-based biofuels and bioproducts, a lot of challenges need to
be overcomed. The possible prospects of downstream processing of
microalgae biomass will aid to achieve more desirable high-value
compounds and thereby creating noteworthy progress towards the fu-
ture of microalgae-based biotechnology.
CRediT authorship contribution statement
Doris Ying Ying Tang: Writing - original draft, Visualization. Kuan
Shiong Khoo: Writing - review & editing. Kit Wayne Chew:
Conceptualization, Supervision. Yang Tao: Supervision. Shih-Hsin Ho:
Supervision. Pau Loke Show: Supervision, Funding acquisition.
Declaration of Competing Interest
The authors declare that they have no known competing financial
interests or personal relationships that could have appeared to influ-
ence the work reported in this paper.
Acknowledgments
This work was supported by the Fundamental Research Grant
Scheme, Malaysia [FRGS/1/2019/STG05/UNIM/02/2] and Jiangsu
Agricultural Science and Technology Innovation Fund (No. CX(19)
3076).
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