Los colores de la biotecnología

PROFESOR IRVING GÓMEZ

 FEMS Microbiology Letters, 365, 2018, fny239

doi: 10.1093/femsle/fny239
Advance Access Publication Date: 25 September 2018
Minireview

M I N I R E V I E W – Biotechnology & Synthetic Biology

The colors of biotechnology: general overview

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and developments of white, green and blue areas
Mayara C. S. Barcelos† , Fernanda B. Lupki, Gabriela A. Campolina,
David Lee Nelson and Gustavo Molina∗
Graduate program in Food Science and Technology (PPGCTA), Institute of Science and Technology, UFVJM,
Diamantina, Minas Gerais, Brazil
∗
Corresponding author: ICT, UFVJM, Rodovia MGT-367 - Km 583, no 5000 - Alto da Jacuba, 39100000, Brazil. Tel: +55-33-3529-2700;
E-mail: gustavomolinagm@gmail.com
One sentence summary: The review presents recent advances and applications of three main areas of biotechnology, namely industrial, agricultural and
marine biotechnology, respectively, known by the colors white, green and blue.
Editor: Colin Harwood
†
Mayara C. S. Barcelos, http://orcid.org/0000-0002-2300-0172

ABSTRACT
Biotechnology is responsible for the manipulation of living organisms or their components for the production of products
that are of benefit to human kind. Due to the wide range of applications, colors have been used to differentiate the main
areas of research, such as white (industrial), green (agricultural) and blue (marine and fresh-water), among others. Thus,
this review outlines the impacts of these areas of biotechnology, emphasizing their impact and potential to replace
carbon-based technologies with more sustainable technologies.

Keywords: bioprocess; bioingredients; industrial development; modern biotechnology; genetic engineering; biotechnology
rainbow

INTRODUCTION among others. More recently, insect biotechnology, an emerging

field of applied entomology that covers the use of insects in drug
Biotechnology is the manipulation of living organisms, systems
discovery, has been coded yellow. In this perspective, the current
and process for the benefit of society, the environment and in-
review focuses on three of these areas, namely white, green and
dustry (Kafarski 2012; Merriam-Webster 2016).
blue biotechnology.
The global biotechnology market has grown over the last few
years, fueled by economic recovery, increased research funding
and government initiatives. The US is first country in the devel- WHITE BIOTECHNOLOGY: POTENTIAL
opment and consolidation of biotechnology; however, develop- OF INDUSTRIAL BIOTECHNOLOGY
ing countries such as India and Brazil are becoming promising
White biotechnology focuses on the production and process-
markets at the biotechnology field, in particular agricultural and
ing of chemicals, materials and energy using living cells, such
industrial biotechnology (Ramos, Melo and Silva 2016).
as yeast, fungi, bacteria, plants and enzymes for the industrial
Kafarski (2012) developed a color code to differentiate the
scale synthesis of products (Glaser 2005; Lorenz and Zinke 2005;
main areas of biotechnology: white (industrial), green (agri-
Ribeiro, Coelho and Castro 2015).
cultural), blue (marine and fresh-water), red (pharmaceutical),
It seeks to reduce the environmental impact moving from
brown (desert biotechnology), purple (patents and inventions),
oil-based to sustainable processes. It is estimated that the use

Received: 6 February 2018; Accepted: 22 September 2018


C FEMS 2018. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

1
 2 FEMS Microbiology Letters, 2018, Vol. 365, No. 21
of industrial biotechnology can lead to the reduction of carbon
dioxide emissions by as much as 50%, energy consumption by
20% and water consumption by 75% (Villadsen 2007). It can also
lead to a 10%–50% reduction in capital and operating costs (Bu-
rel 2000). Forecasts for 2020 report a market valued at approxi-
mately US$95 billion, including biofuels, production of various
chemicals and bioplastics (Erickson, Nelson and Winters 2012).
Current main applications of white biotechnology
Production of several chemical ingredients
The production of bulk chemicals such as organic acids and al-
cohols by white biotechnology contributes to savings in energy,
a reduction of gas emissions and the assurance of industrial in-
novation and supply (Hermann, Blok and Patel 2007). This factor
is an important feature in the recent development of large-scale
processes (Villadsen 2007).
Organic acids, such as citric acid, lactic acid and acetic acid,
represent the main food additives currently produced at indus-
trial scale using white biotechnology. Citric acid, mainly pro-
duced by Aspergillus niger, is commercially the most important
product with a market value of US$1.4 billion (Carvalho et al.
2005).
Another important class is the sweeteners, such as xylitol,
sorbitol and aspartame. The global demand for these sweeten-
ers has significantly increased in recent years in response to
consumer demand for products with zero calories. Using a com-
bination of synthetic biology and biotechnology, new metabolic
pathways can be synthesized for the production of novel prod-
ucts (Philippe et al. 2014).
Patel (2006) divided the primary chemicals according to the
amount of carbon present in the molecule, citing the main
alcohols, organic acids and polysaccharides of industrial and
biotechnological importance. The biotechnological production
of these compounds, along with their substrates and production
scales, can be seen in Table 1.
Other major products include amino acids and vitamins,
some of which are produced entirely or almost entirely by white
biotechnology. Amino acids are molecules of importance both
for humans and for animals as they comprise proteins and have
a respectable role in metabolic processes. There are a total of 20
common amino acids, divided into essential and non-essential
amino acids (Mitsuhashi 2014).
Essential amino acids are those that are not synthesized
by humans. These essential amino acids are valine, leucine,
isoleucine, lysine, threonine, methionine, histidine, phenylala-
nine and tryptophan, together with the non-essential amino
acid glutamate, are of great economic and industrial importance
(Leuchtenberger, Huthmacher and Drauz 2005). Currently, pro-
duction of amino acids is the second most commercially impor-
tant white biotechnology process, with an annual growth esti-
mate at 7% (Leuchtenberger, Huthmacher and Drauz 2005).
Glutamate, commonly used as a flavor enhancer, is the main
amino acid produced commercially. It is it is synthetized from
carbohydrates using Corynebacterium glutamicum, with some
industrial processes achieving yields of 100 g/L (Becker and
Wittmann 2012).
Lysine is the main amino acid additive for animal feed. It is
also produced by C. glutamicum, using glucose derived from the
enzymatic treatment of corn starch or sugar syrup, or, as sug-
gested in some studies, from lignocellulosic biomass. With glu-
cose as the carbon source, yields of 6.04 g/L have been reported
(Mitsuhashi 2014).
The main amino acids produced by white biotechnology, as
well as the substrate and the average production scale, are pre-
sented in Table 2.
Vitamins are essential micronutrients that are not synthe-
sized by mammals and must be obtained exogenously, being di-
vided into two groups: fat-soluble and water-soluble (Survase,
Bajaj and Singhal 2006).
The vitamins E and K2 are the main representatives of the
fat-soluble group. Vitamin E is an important antioxidant obtain
from chemical synthesis, extraction from oils and by biotech-
nology, with reported yields of 1.21 g/L (Abalde, Fabregas and
Herrero 1991). While vitamin K2 is an important cofactor for the
conversion of glutamic acid residues of specific proteins in blood
(Sato et al. 2001).
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The water-soluble vitamins produced biotechnologically are
represented by ascorbic acid, biotin, riboflavin and vitamin B12 .
Ascorbic acid is necessary for different metabolic processes and
is an antioxidant; biotin is known to be a cofactor involved in
central pathways in pro- and eukaryotic cell metabolism; ri-
boflavin is used for human nutrition, having its deficiency linked
to hair loss, vision deterioration and growth failure, and the pro-
duction of vitamin B12 is restricted to microorganisms (Survase,
Bajaj and Singhal 2006).
The main vitamins produced by white biotechnology, sub-
strate and production scale are presented in Table 3.
Industrial production of biofuels and bioenergy
Biofuels are produced from renewable organic substrates and
even organic debris, which represents an important option for
medium- and long-term replacement of fossil fuels. They aid
in maintaining the economic and environmental sustainabil-
ity and can be divided into gaseous (methane, hydrogen and
hythane) and liquid (ethanol, butanol and diesel) biofuels, these
being the main representatives obtained by white biotechnology
(Taylor 2008; Zhang et al. 2016).
Gaseous biofuels are the result of anaerobic degradation of
organic matter that may be present in agricultural, urban and
food waste (Martins 2004), while liquid biofuels, which have pro-
cessing characteristics similar to those of gasoline, diesel and
other fossil fuels are produced from various biomasses. Liquid
biofuels are preferred since it reduces gas emissions by up to 90%
and can be used in the transportation sector with only modest
changes in vehicle technology (Zhang et al. 2016).
The biofuels sector is divided into first and second generation
processes. First generation biofuels are produced from sugars,
grains or seeds and require a relatively simple process, whereas
second generation are produced by biological or thermochem-
ical processes using lignocellulosic biomass, which can be de-
rived from food or farm waste or whole plants (Taylor 2008;
Zhang et al. 2016). Ethanol is currently the main product, using
as carbon substrates such as sugarcane (Brazilian model), corn
(North American model), and lignocellulosic materials from
agro-industrial organic wastes (Hahn-Hägerdal et al. 2006; Soc-
col et al. 2009). The steps for obtaining industrial ethanol from
the principal raw materials are shown in Fig. 1.
Among gaseous biofuels, methane production has been ex-
tensively studied from food residues, with an estimated produc-
tion of 29.5 GW for 2022 (Zhang et al. 2014; Mao et al. 2015; Rasit
et al. 2015).
The importance of biopolymers for the future of the industry
Polymers are macromolecules that are extremely versatile and
diverse in structure, being constructed from small monomeric
molecules. The properties of each polymer are dependent on the
 Barcelos et al. 3

Table 1. Biotechnological production of the main chemical products, the starting materials and the production scale using white biotechnology.

Biotechnological
production Substrate Production scale Applications Reference

C2
Ethanol 90% of the world Biomass such as Rate of Food industry, (Lennartsson,
production by sugarcane and production: 1 g/L. chemical sector, Erlandsson and
fermentation using corn kernels World fuel and fuel Taherzadeh 2014;
biomass with a yield production: additives Patel 2006)
estimated as 86.1 × 106 m3
90%–95%

Acetic acid Bulk form: Ethanol World Chemical and (Carvalho et al. 2005;
synthesized by production: food industry Patel 2006)

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carboxylation of 190.000 tons/year
methanol
Food industry:
fermentation

C3
Lactic acid Homolactic or Yeast extract Production rate: Food and (Carvalho et al. 2005;
heterolactic 771 g/L beverage Guilherme, Pinto
fermentation with a World industry; and Rodrigues 2009;
yield greater than production: industrial Patel 2006)
90% 390.000 tons/year applications;
pharmaceutical
and personal
care products.

Glycerol Byproduct of the Fats and oils – Chemical (Patel 2006)

processing of fats industry. Low
and oils; it can also cost makes
be produced with oil–chemical
the aid of enzymes reactions
or fermentation. attractive
As a byproduct, its
cost is relatively low:
US$1.000/ton.

3-Hydroxypropanoic acid Fermentation Glucose and – Production of (Patel 2006)

route:100% yield is glycerol other chemical
possible from products of
glucose using industrial
genetically modified interest
micro-organisms

1,3-propanodiol Fermentation route Glucose and – Production of (Patel 2006)

with 51%–55% yields glycerol biopolymers
utilizing genetically
modified
microorganisms

Acrylic acid Biotechnological – – Production of (Patel 2006)

route developed biopolymers
with genetically
modified
microorganisms

C4
Succinic acid Fermentation of Sugars – Chemical, (Erickson, Nelson
carbohydrates pharmaceutical, and Winters 2012;
food and Patel 2006)
agricultural
industries
 4 FEMS Microbiology Letters, 2018, Vol. 365, No. 21

Table 1. Continued.

Biotechnological
production Substrate Production scale Applications Reference

Fumaric acid Small scale Sugars Estimated Food acid, (Patel 2006)
fermentation of production of ingredient in
carbohydrates 12.000 ton/year beverages and an
with an expected additive in
growth to animal feed.
120.000 ton/year

Aspartic acid Fermentation and Sugars Estimated Used for the (Patel 2006)
enzymatic route production of production of
10.000 ton/year sweeteners and
with a market polymers

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value of $43
million

1-butanol Fermentation, but Sugars Market Mainly used as a (Erickson, Nelson

with low estimated in one solvent and Winters 2012;
concentrations and billion dollars Patel 2006)
yields

1,4-Butanediol Can be obtained by Cellulosic Market Intermediate for (Erickson, Nelson

fermentation of biomass estimated in the production of and Winters 2012;
succinic acid three billion polymers in the Patel 2006)
dollars chemical
industry.

C5
Xylose, arabinose and xylitol Obtained from Lignocellulosic – Sweeteners and (Patel 2006)
lignocellulosic biomass the production of
biomass by other products
thermomechanical
treatment, and acid-
and enzyme-
catalyzed hydrolysis

C6
Sorbitol Fermentation, but Sugars – Sweeteners, (Patel 2006)
economically antimoisturizer
unattractive due the and precursor to
facility of chemical other chemical
synthesis products

5-Hydroxymethyl furfural Enzymatic hydrolysis Sugars – – (Patel 2006)

Adı́pic acid Biosynthesis or Glucose – Production of (Patel 2006)

enzymatic conversion Nylon 66

type of monomer used, their sequence and the polymerization
process employed (Mülhaupt 2013). To meet the needs of today’s
society, the concept of biopolymers obtained by white biotech-
nology is important since such materials have become essential
components in any type of consumer product that meets the di-
verse domestic and industrial demands (Andrady 2003).
Biopolymers can be obtained from natural sources (e.g. cellu-
lose) or natural monomers by biotechnological polymerization.
Among the biotechnological polymers, the most widely known
and used are biopolyesters, such as polylactic acid and poly-
hydroxybutyric acid (PHB), produced by bacteria or transgenic
plants on a large scale. They are fully biodegradable, releasing
water and carbon dioxide into the environment (Poirier 1999).
The first major industrial development occurred in 2009,
when the Coca-Cola company marketed composite plastic bot-
tles made of 30% ethylene glycol biomonomers and recycled PET.
The 100% renewable bottles also have terephthalic acid in their
composition. The company has announced that this initiative
has eliminated the issuance of approximately 315 million tons
of carbon dioxide (Coca-Cola 2015). Data from 2016 reported that
biopolymers represent around 1% of all the polymers produced
today, and the market of 1.7 million tons is expected to increase
to 7.8 million tons in 2019 (Bioplastics 2016).
The biopolymer field has undergone drastic evolutions, aim-
ing to supply the industry with new biopolymers and allow-
ing several innovations in commercial applications. The main
biopolymers obtained by white biotechnology include diols (e.g.
ethyleneglycol, propane-1,3-diol, butane-1,4-diol), dicarboxylic
acids (e.g. succinic acid and terephthalic acid), alkyl amines,
amino acids, furans and several important hydroxyalkanoic
 Barcelos et al. 5

Table 2. Biotechnological production of the principal amino acids, substrate and production scale using white biotechnology.

Biotechnological
production Substrate Production scale Reference

Valine, leucine Produced by genetically – – (Becker and Wittmann

and isoleucine modified Corynebacterium 2012)
glutamicum

Lysine Produced by genetically Glucose or lignocellulosic 1.3 million tons/year (Mitsuhashi 2014)
modified Corynebacterium biomass
glutamicum

Threonine Produced by E. coli - Projection of 70.000 tons (Leuchtenberger et al. 2005)

Methionine Produced by Glucose, ammonium Mean yield of 3 g/L, an (Krömer et al. 2006; Kumar

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Corynebacterium glutamicum sulfate estimated production of et al. 2005; Mitsuhashi 2014)
genetically modified with E. 400.000 tons and a market
coli or C. lilium value of US$ 2.2 billion

Histidine Produced by genetically – Yield of 8 g/L (Mitsuhashi 2014)

modified Corynebacterium
glutamicum

Phenylalanine Produced by fermentation Glucose Yield of 25 g/L (Leuchtenberger et al. 2005)

with E. coli

Tryptophan Produced by E. coli Glucose Projected production of (Leuchtenberger et al. 2005)

3.000 tons

Glutamate Produced by Carbohydrates 2 million tons/year and a (Becker and Wittmann

Corynebacterium glutamicum yield of until 100 g/L 2012; Becker et al. 2011)

Table 3. Biotechnological production of fat-soluble and water-soluble vitamins, substrate and scale of production using white biotechnology.

Biotechnological production Substrate Production scale Reference

Fat-soluble
Vitamin E Production by fermentation Glucose – (Takeyama et al.
using the microalga Euglena 1997)
gracilis

Vitamin K2 Produced by fermentation Soy extract – (Sato et al. 2001)

with genetically modified
Bacillus subtilis

Water-soluble
Ascorbic acid (Vitamin C)
Fermentation process by Glucose Estimated market (Boudrant 1990;
2,5-diketo-D- glutamic acid value of US$ 585 Hancock and Viola
reductase and Cynobacterium million and 2002; Survase et al.
sp. production of 80 mil 2006)
ton/year

Biotin Fermentation process with Glucose Production of 10–30 (Gloeckler et al. 1990;
genetically modified Bacillus ton/year Survase et al. 2006)
subtilis, Serratia marcescens
and a multi-enzyme system

Riboflavin Fermentation process with Glucose – (Horiuchi and Hiraga

Eremothecium ashbyii, Ashbya 1999)
gossypii and Bacillus sp.

Vitamin B12 Fermentation process with Glucose – (Marwaha, Sethi and

Propionibacterium shermanii Kennedy 1983)
and Pseudomonas denitrificans.
Obtained exclusively by
white biotechnology
 6 FEMS Microbiology Letters, 2018, Vol. 365, No. 21
Figure 1. General steps used for the production of ethanol from the principal raw plant materials (Adapted from Soccol et al. 2009).
acids (such as L-lactic acid, a very representative compound for
the area; Mülhaupt 2013).
Other compounds obtained for industrial purposes
Other products of great economic and industrial interest to
white biotechnology are enzymes, flavors and surfactants,
among several others. Industrial scale processes and microor-
ganisms are already well defined to produce enzymes, whereas
flavors and surfactants represent great prospects for the field.
The principal enzymes of industrial interest are used primarily
for the conversion of starch and in processes such as baking,
fruit processing, dairy and brewing. Classes such as amylases,
proteases, oxidases and lipases may be cited as examples. The
global enzyme market was valued at US$2.9 billion in 2008, ris-
ing to US$4.4 billion in 2015, an increase of about 6% per year
(Erickson, Nelson and Winters 2012).
Aroma compounds represent a very important class in var-
ious fields such as food, pharmaceutical and cosmetics (Forti
et al. 2015). The production of aromas via white biotechnology
offers an alternative to chemical processes and natural extrac-
tion, and it is performed under mild conditions with high speci-
ficity (Molina 2010). A market of US$24.7 billion exists in 2016,
and growth is expected for the coming years (Leffigwell 2016).
Surfactants act as detergents and are able to reduce the sur-
face tension between molecules to increase their bioavailability
and biodegradability. They are produced mainly by the petro-
chemical industry. Alternatives to this process are available, pro-
ducing biosurfactants that have a better performance and are
‘eco-friendly.’ However, the technology is still expensive, neces-
sitating further research and developments in the area (Pater-
mann 2010).
As may be seen, white biotechnology represented an im-
portant area of biotechnology that seeks to obtain sustainable
development through new technologies, reducing the environ-
mental impact and furnishing maximum efficiency and effec-
tiveness for various industrial processes. The total production of
some compounds already occurs through biotechnological pro-
cesses on an industrial scale, such as some vitamins and simple
chemical compounds, presenting advantages, such as the avoid-
ance of toxic waste and economy of energy, opening many prece-
dents for the future of sustainable industry.
GREEN BIOTECHNOLOGY: POTENTIAL FOR
SEVERAL SECTOR OF AGRICULTURE
Green biotechnology seeks to reduce the dependence of agri-
culture on mechanical and chemical innovations by using less
aggressive practices to the environment and contribute to the
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emergence of better food, increased productivity and reduced
production costs (Silveira, Borges and Buainain 2005).
Among the applications for green biotechnology, the de-
velopment of transgenic and genetically modified organisms
(Silveira, Borges and Buainain 2005; Ribeiro, Coelho and Cas-
tro 2015), power generation and the prevention of environmen-
tal pollution by the production of biopolymers from renewable
resources (Schenberg 2010), among others can be highlighted.
Below, some examples that illustrate the developments and
progress of green biotechnology in different sectors are pre-
sented.
Main applications of green biotechnology
Transgenic or genetically modified organisms
The main contribution of modern biotechnology to agriculture
is the possibility of creating new species by the transfer of genes
between different organisms to develop a plant of technological
or economic interest (Silveira, Borges and Buainain 2005).
The first GM plants were developed in 1983, and the first
permission for experimental planting only occurred in 1990 in
China (Guerrante 2003). However, the use of GM crops for com-
mercial purposes on a large scale only began with the Flavr savr
tomato in the United States in 1992 and later, in 1996, with the
Roundup Ready soybean (Silveira, Borges and Buainain 2005).
The main characteristics of GM crops are insect resistance
and herbicide tolerance, increasing productivity and plant toler-
ance to adverse soil and climate conditions (James 2014).
Roundup Ready soybean (RR soybean),a herbicide-tolerant
GM crop, developed with the introduction of a glyphosate
resistance gene of Agrobacterium tumefaciens bacteria in its DNA
makes the soybean resistant to the Roundup R herbicide (Sil-
veira, Borges and Buainain 2005). This herbicide, through its
glyphosate component, kills weeds by blocking the enolpyru-
vyl shikimate-3-phosphate synthase enzyme responsible for the
production of essential amino acids for growth and survival of
most plants (Krimsky and Wrubel 1996; Daniele et al. 1997).
Bt cotton and Bt maize, insect resistant crops, have genes
encoding insecticidal activity from the bacterium Bacillus
thuringiensis (Bt; Silveira, Borges and Buainain 2005; James 2014)
The proteins derived from these genes are specific in confer
resistance to certain Lepidoptera species (Armstrong et al. 1995;
Huang et al. 2002). Before they can cause damage to the crops,
caterpillars feeding on these GM crops ingest the Bt protein,
which then acts on the gut epithelial cells to promoting osmotic
rupture and death. The main appeal of these products is to facil-
itate the management of the crop, reduce production costs and
increase the value in Integrated Pest Management programs,

giving farmers a greater certainty in combating the pests (Huang
et al. 2002; Silveira, Borges and Buainain 2005).
Between 1996 and 2015, there was a 100-fold increase in
the areas of GM crops planted from 1.7 million hectares to
179.7 million hectares. This technology is considered to repre-
sent the most rapidly adopted agricultural technology in mod-
ern agriculture history (James 2014).
Currently, the United States (73.1 million hectares), Brazil
(42.2 million hectares), Argentina (24.3 million hectares), India
(11.6 million hectares) and Canada (11.6 million hectares) are
among the largest producers of GM crops in the world by area. In
addition to these countries, another 23 countries complete the
list of GM producers with a total of 28 producing countries and
18 million farmers. The crops most frequently grown are corn,
soy, cotton and canola (James 2014).
On average, the adoption of GM crops has reduced the use of
chemical pesticides by 37%, increased crop yields by 22%, lead-
ing to an increase in profits of farmers by 68% and generated
an increase in crop productivity of approximately US$133.3 bil-
lion from 1996 to 2013 (James 2014). These increases ensured
the competitiveness of food-exporting countries in agribusiness
markets (Gomes and Borém 2013).
During the next 5 to 10 years, in addition to currently mar-
keted GM crops (soybeans, corn, cotton, canola, sugar beets,
alfalfa, squash, papaya, poplar and eggplant), new crops may
become available. These crops are likely to include apples, ba-
nanas, cameline, cassava, citrus, chickpea, cowpea, ground-
nuts, mustard, pigeon pea, potato, rice, safflower, sugarcane and
wheat. The range of features aimed at improving drought and
salinity tolerance, improving yield and efficiency of nitrogen uti-
lization, which increase nutrition and food quality and resis-
tance to pests and diseases, including resistance to virus, rep-
resents a vast development potential for the area (James 2014).
Power generation using green biotechnology tools
Green biotechnology operates by increasing productivity and the
development of adaptive plants with greater energy potential,
seeking, among other things, the production of biofuels (Beer
et al. 2009).
New research has been developed to increase the production
of ethanol. An example is the improvement of sugarcane, where
green biotechnology hopes to develop clones with high produc-
tivity, high sucrose content, drought tolerance, high content of
cellular fibers and walls that are easily broken, so as to promote
the production of ethanol and reduce environmental impacts
(Morais et al. 2015).
In addition to the genetic improvement of plants for the pro-
duction of ethanol, green biotechnology is also active in the
genetic improvement of raw materials for biodiesel produc-
tion, such as the soy and castor beans, seeking the selection of
genotypes resistant to major pests and diseases specific to the
climate and altitude, and the stimulation of early growth and
develop plants suitable for different harvest technologies, espe-
cially grains that have higher oil contents (Severino et al. 2008;
De Vasconcelos et al. 2012; Leite 2015). The use of plant growth-
promoting rhizobacteria is also an alternative for biocontrol of
plant pathogens, presenting advantages over chemicals avoid-
ing crops losses and promoting plant growth promotion (Tabas-
sum et al. 2017).
Furthermore to the efforts to increase the productivity of
first and second generation biofuels, the scientific community
has focused its attention on the development of renewable en-
ergy from different biological sources, especially microorgan-
Barcelos et al. 7
isms (third generation (3 G) biofuel; Mutanda et al. 2011; Maria
and Machado 2013).
Production of biopolymers using green biotechnology
The biopolymers may be of plant origin, such as algae (algi-
nate, agar, carrageenan), seeds (guar gum and locust) and trees
or their exudates (gum karaya and gum arabic). Other sources
are microbial biosynthesis products (xanthan gum, gellan, dex-
tran, curdlan), or chemical modification of natural polysaccha-
rides (pectin, gelatin, starch, sodium carboxymethylcellulose;
Yu, Dean and Li 2006).
Just as in the production of biofuels, green biotechnology
is active in plant breeding for the production of biopolymers.
The modification of starch from vegetable sources such as corn
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and potato starches can be employed to obtain raw materials
that possess greater stability to storage conditions and less sus-
ceptibility to variations in humidity and that can be degraded
faster (Mali, Grossmann and Yamashita 2010). The most impor-
tant biopolymers are polylactide, polyhydroxyalkanoate, starch
polymers and xanthan gum (Pradella and Nacional 2015).
The biopolymer industry is researching the use of non-food
crops and by-products such as straw and bagasse (second and
3 G raw materials) for its production using biotechnological pro-
cesses. Along with the growing variety of biopolymers, prop-
erties such as flexibility, durability, transparency, barrier, heat
resistance, gloss and more are being significantly enhanced
(Bioplastics 2016).
The selling price of biopolymers is up to 50% higher than
the market prices of the most common synthetic polymers
(Borschiver et al. 2008). The price is expected to decrease from
20% to 25% in the next 5 years, whereas the price of polymers
obtained from oil is expected to increase as a consequence of
the increased demand and oil prices (Pereira et al. 2013).
Thus, rapid population growth has increased the demand for
food, energy, fuel, medicines and various materials (plastics, fab-
rics, paper and inks). To supply this demand, agriculture is of
fundamental importance in providing a large amount of raw ma-
terials used by industries. Green biotechnology can contribute
positively to the increased supply of products of the utmost ne-
cessity, improving the quality and safety, and reducing environ-
mental impacts. It acts by creating better quality raw materials,
more resistant to attack by pests and furnishes higher yields,
with better quality and significantly increased production, as
well as reducing the time and costs of operation and other char-
acteristics.
BLUE BIOTECHNOLOGY: MARINE
BIODIVERSITY AS SOURCES OF ESSENTIAL
COMPOUNDS
Blue biotechnology or marine biotechnology seeks to explore
and use marine biodiversity as a source of new products, bio-
prospecting the environment and using molecular biology and
microbial ecology in marine organisms to obtain beneficial
advances for humanity (Tramper et al. 2003; Querellou 2010;
BIGELOW 2016; EUROPEANCOMISSION 2016).
The proteins and enzymes from marine organisms are ex-
tremely important for industrial biotechnology, with a potential
to contribute to the development of new processes in the food
and pharmaceutical industries. The biopolymers of marine ori-
gin, for example, have been used in biodegradable plastics, phar-
maceutical and medical products, bio-adhesives and dental bio-
materials (Querellou 2010).
 8 FEMS Microbiology Letters, 2018, Vol. 365, No. 21
Table 4. Bioactive compounds extracted from marine organisms and approved by the FDA.
Marine organism/species Bioactive compound
Sponge/Tethya crypta Cytarabine
Sponge/Tethya crypta Cytarabine liposomal
Sponge/Tethya crypta Vidarabine
Snail/Conus magus Ziconotide
Ecteinascidia turbinata Trabectedin
Source: Adapted from Gordaliza, 2007; Newman, Cragg and Battershill 2009.
In 2010, the global market for marine biotechnology was es-
timated at 2.8 billion euros, with an annual growth rate of 4% to
5% (Querellou 2010).
Main applications of blue biotechnology
Potential for novel bioactive compounds production
Exploration of the marine environment has resulted in the dis-
covery of several substances from marine organisms, where the
production of drugs becomes a reality at pharmaceutical in-
dustries. Among these substances, the carotenoids, polyunsatu-
rated fatty acids, proteins and enzymes can be emphasized (Pulz
and Gross 2004; De Jesus Raposo, De Morais and De Morais 2013;
Murray et al. 2013), as well as bromoditerpene, gambieric acid
and the AD marinomycines, among others. These products can,
for example, be applied in the pharmaceutical industry in the
form of antioxidants, antibiotics, analgesics, antitumor, anti-
inflammatory and antifungal agents (Murray et al. 2013).
Among the numerous marine organisms with a potential for
the production of bioactive compounds, the macro and micro-
algae, sponges, fungi and marine yeast can be highlighted.
The bioactive compounds can be produced from cultures using
photo bioreactors under controlled conditions (CO2 , light, nutri-
ents and physicochemical parameters; Pulz and Gross 2004; Ror-
rer and Cheney 2004) or be induced by genetic transformations.
Chemical methods, enzymatic hydrolysis, extraction of natural
products with solvents and mechanical pressure are employed
as methods for extraction of the bioactive compounds (Murray
et al. 2013).
Most of the bioactive compounds from marine organisms
are still in the research and clinical trials stage, as stated
earlier. These studies can take years until the substances are
approved by competent authorities, but some drugs have been
incorporated and approved by the FDA (Food and Drug Adminis-
tration), as is the case with Prialt
R analgesic (Jazz Pharmaceu-
ticals, USA), Yondelis R (Pharma Mar S.A, Madrid, Spain) antitu-
moral , the Cytosar-U R (Upjohn, USA) anticâncer agent (Mayer
et al. 2010). Each of these drugs has already been marketed. The
bioactive compound, application and the marine organism from
which the compound is extracted are presented in Table 4.
Food industry applications
In the food industry, marine biotechnology is mainly used for
the production of additives and pigments from cyanobacteria,
macroalgae and, especially, marine microalgae. Marine microal-
gae are capable of producing polyunsaturated fatty acids (Batista
et al. 2014), lutein (Sánchez et al. 2008), astaxanthin (Tripathi et al.
1999) and β-carotene (Qin, Liu and Hu 2008), while cyanobacteria
were reported as producer of phycocyanin (Pulz and Gross 2004).
Is noteworthy that the process of obtaining compounds of in-
terest from the algal biomass depends on the raw material used
and the product of interest. The conditions of the process and
the techniques employed may vary from case to case.
Application/indication Commercial name
Treatment of leukemia Cytosar-U R
Treatment of lymphomatous meningitis Depocyt R
Antiviral Vira- AR
Analgesic Prialt
R
Antitumoral Yondelis R
A large part of the microalgae applied to food products are
grown for biomass production and subsequent application. Ap-
plications may include nutritional supplementation, mainly by
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lipids (glycerol and fatty acids), carbohydrates (sugars, starch,
cellulose and other polysaccharides) or pigments (chlorophyll,
carotenoids, etc.; Becker 2004).
In most cases, the biomass produced for food applications
is applied in powder form. Also, the health benefits (prebiotic
effects, mineral fortification or supplementation) can be com-
bined with the attractiveness of the product for the consumer.
Few years ago, countries like Germany, France, Japan, USA, China
and Thailand applied the powder microalgae in pasta, breads
and yogurts (Pulz and Gross 2004).
However, there are still some challenges related to the pro-
duction of algal biomass because of the dependence on factors
such as light intensity, temperature, pH, nutrients and agitation
(Miao and Wu 2004). The development of research related to the
interaction of these factors can reflect directly on the optimiza-
tion of the cultivation of microalgae and, consequently, on the
compounds synthesized by the algae (Duarte 2001).
Cosmetic industry
Marine biotechnology plays an important role in the cosmetics
industry, presenting some new compounds to the production
of cosmetics (Vivó-Sesé and Pla 2007). Some of these cosmet-
ics in which marine compounds are incorporated have been ob-
tained biotechnologically and are already being marketed. As an
example, the DG-DNA Complex R is one of the components in
the Micrococcus lysate enzymatic extract. The Micrococcus is de-
rived from the soil and oceans and has a high resistance to UV
radiation. Moreover, it contains the UV-endonuclease enzyme,
which accelerates the recovery from sun damage and acts in
DNA repair. Currently, this compound is included in face creams
(Emiliano, Guimarães and Netz 2012). The production of com-
pounds used in the cosmetic formulation is usually performed
by isolation from a species of microalgae or other marine organ-
ism, followed by cultivation in photobioreactors (BIOTECHMA-
RINE 2016). Table 5 shows several examples of marketed cosmet-
ics that employ marine biotechnology as part of their processes.
In addition to those mentioned companies, several other pro-
duce compounds from marine biotechnology for applications in
cosmetics, such as Mibelle Biochemistry R
and GreenaltechR
.
Although there are several companies of the cosmetic sec-
tor investing in marine biotechnology, few scientific studies ex-
ist in the area. Therefore, these studies should be encouraged to
improve production techniques and the application of the com-
pounds synthesized from marine organisms.
Biofuels originated from marine resources
Biofuels of marine origin are derived from macro- and microal-
gae and have emerged as an alternative to the use of land plants
(Cunha 2012; Hargreaves 2012). Being produced from marine al-
gae, they also have the advantage of been easily grown water,

Table 5. Cosmetics produced by marine biotechnology.
Marine Organism Species Product
Macroalga Undaria Pinnatifida Ephemer Anti-aging
Microalga N.I. Silidine Reduce the dilation of blood vessels and the redness in legs.
Macroalga N.I. Xcell-30 Anti-aging and active against psoriasis and dandruff
N. E. N.I. Cellynkage Anti-aging
∗
N.I.: not informed by the manufacturer. ∗∗ N.E.: not found.
Source: BIOTECHMARINE 2016; GreenTech 2016; LIPOTEC 2016.
do not compete for agricultural areas and do not require the
use of chemical fertilizers (Defanti, Siqueira and Linhares 2010;
Hargreaves 2012). They have high productivity (Georgianna and
Mayfield 2012) and do not use food-based raw materials (Defanti,
Siqueira and Linhares 2010).
The yields of marine biofuels are 10 to 100 times greater than
the common biofuels produced from land plants per unit area.
However, despite the high yield, the high costs of these pro-
cesses (transesterification, centrifugation, filtration, extraction,
fermentation, etc.) represent a challenge to the economic viabil-
ity of biofuels of marine origin (Mota and Monteiro 2013).
The most extensively produced biofuel by marine biotech-
nology is bioethanol, known as 3 G ethanol. It is produced from
algal biomass, primarily through the fermentation process, and
it has received more emphasis than other biofuels produced
from algae (Goh and Lee 2010). Processes using various species of
marine microalgae for biofuel production have achieved yield of
65.50 g/L (Kappaphycus alvarezii; Hargreaves 2012), 34.40 g/L (Ulva
pertusa Kjellman; Yanagisawa et al. 2011), 30.00 g/L (Alaria crassifo-
lia Kjellman; Yanagisawa et al. 2011), 29.00 g/L (Laminaria japônica;
Kim et al. 2011), and less than 10 g/L (Chlorococum humicola and
Chlorococum sp.; Harun and Danquah 2011).
Thus, the potential and increasing importance of the use and
application of blue biotechnology in the drug, food, cosmetics
and biofuel industries is clear. Despite being a relatively new
area, marine biotechnology has achieved good results and has
demonstrated the feasibility of its application. In most sectors,
many currently marketed products involve the inclusion of ma-
rine biotechnology. However, a great opportunity for expansion
could be observed in all the sectors if the investments to improve
the techniques and processes continue progressing.
CONCLUSION
The potential of biotechnology is the focus of the development
of several agroindustry sectors, and its tools have enabled the
rapid evolution of numerous products and processes of com-
mercial and economic interest. In this sense, one of the new di-
visions of biotechnology has been carried out by color, aiming
to categorize according to the sector of application, the biotech-
nology tools. The white biotechnology seeks the production of
products of industrial interest, such as chemical bulks, amino
acids, polymers, vitamins and much more using new develop-
ment processes with high yields and mild process conditions,
which can lead to a greater economy during the production.
Meanwhile, the application of green biotechnology in agriculture
has increased crop production, food diversity and energy gener-
ation, always aiming at quality and reducing negative impacts
to the environment. The use of these technologies has led to an
evolution in agricultural practices, besides being a technology
with ample growth potential. Finally, blue biotechnology aims
to explore and apply marine biodiversity into new products. The
Barcelos et al. 9
Application in cosmetics Firm
BiotechMarine
R
Greentech
R
Greentech
R
Lipotec
R
main applications of these technologies are related to the pro-
duction of antioxidants, antibiotics, antitumor, among others, at
the pharmaceutical industry; facial creams at cosmetics; addi-
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tives and pigments for the food industry and 3 G ethanol for the
biofuels industries. Despite being relatively new, blue biotech-
nology has a promising twist within the field of biotechnology
and has good growth prospects.
ACKNOWLEDGEMENT
Authors acknowledge the agencies ‘Conselho Nacional de De-
senvolvimento Cientı́fico e Tecnológico’ (CNPq), ‘Fundação de
Amparo à Pesquisa do Estado de Minas Gerais’ (Fapemig) and
‘Universidade Federal dos Vales do Jequitinhonha e Mucuri’
(UFVJM).
Ethical Statement: Authors declare that there is no conflict of
interest. This article does not contain any studies with human
participants or animals performed by any of the authors.
Conflict of interest. None declared.
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