**2. Algae metabolism: sterols discovery**

The literature brings information's about diverse algae sterolomic profile, so in this chapter let us begin with the most curious and strong algae, considered the earliest life forms in the world, the prokaryotes microalgae (cyanobacteria). These strains are also known as blue-green algae, they are widely distributed in the world, due to their robustness. Cyanobacteria are considered by biologists a variation from bacteria and eucaryotic strains, which could lead in a production of sterols related with vegetal, and also animal kingdom [3].

Cyanobacteria for this reason, can occur in marine environments with a huge salt variation, in cold waters as Antarctic system, and hot waters, could also proliferate in desert sand and rocks, providing a major response from their metabolic systems modifications according to the natural evolution. These cyanobacteria can produce different metabolites according to the habitat that they are living, for this reason, merging the information's we can understand that they can present many metabolic pathways leading to different end-sterols products. Their resistance comes from their plasmatic membrane associated mostly with structures named hopanoids, that are very similar to sterols, and are responsible for the flexibility of cyanobacteria cellular membrane [4].

The major discussion on the literature is the unknown ability of these organisms producing sterols. Many years ago, some researches described the possibility to exist only hopanoids in their structure, in fact, with the advance in tandem mass spectrometry, nuclear magnetic resonance analysis associated with new extraction techniques it was discovered the presence of sterols in their membrane. Thus, metabolism involved in sterols biosynthesis by cyanobacteria are not totally elucidated.

In the history context, the first works showing sterols production in cyanobacteria were in a filamentous cyanobacteria named as *Phormidium luridum* in 1968 [5], in this study it was isolated unsaturated sterols, like as 24 ethyl sterols, following this research's other studies investigated a way to produce this metabolite in large scale, considering the fact that this cyanobacterium has resistance in front of other microorganisms, inferring a remarkable capability for industrial application.

In the ninety's the researchers Sallal, Nimer, and Radwan [6] studied other cyanobacteria strains, and verified that after dark incubation, sterols concentration increased. In in agreement to this study, Fagundes et al. [7] showed higher concentrations of sterols (β-sitosterol, stigmasterol, and cholesterol), for *Phormidium autumnale* cultured in heterotrophic system, being the inoculum without the presence of these compounds. In general, cyanobacteria are manly photosynthetic, but some strains can growth in heterotrophic conditions, in this context, it can be concluded that more studies on this particular area are necessary for further acquire more comprehension for biotechnological application.

Eukaryotic microalgae are reported in the literature as the most prominent strains for sterols production, and they are important to make feasible membrane cell permeability, and maintain structural protection [8, 9]. In this sense, the study of sterols biosynthesis started in eukaryotic cells, standing out in numerous hypothesis, and one of them is related to life adaptation on earth, showing that these molecules were produced in this cell as a protective response to reactive species of oxygen [10]. The first study in eukaryotic microalgae was in 1960 with *Scenedesmus*, showing as the major compound chondrillasterol [11], years later the same researchers Iwata and Sakurai [12] reported ergosterol as the most abundant sterol for C*hlorella.* In terms of macroalgae, the (brown) species *Ulva lactuca*, and *Cytoceira adriatica* from Adriatic Sea, were analyzed by the authors Kapetanovic et al. [13], showing that these species were the main sterols cholesterol and fucosterol for both algae.

**143**

**Figure 1.**

*docosahexaenoic acid.*

*Sterols Biosynthesis in Algae*

patterns [15].

*DOI: http://dx.doi.org/10.5772/intechopen.96719*

associated with anti-atherosclerotic function [16].

could lead to a sustainable sterols production.

*Principal countries with important algae biotechnology companies' and their products. DHA -* 

In summary algae strain choice directly reflects in their potential for commercial application, for this reason, the knowledge of algal productivity, and the biotechnological treatment applied for each alga is important. So, understand the metabolic pathways for the full comprehension of sterols, and their intermediary metabolites formed provides important information for future culture modifications enhancing specific compounds [14]. For this, depending on the triterpenoid produced they can be applied for medical proposes, which is a great alternative since in the last decade we have the challenge for the isolation of new compounds, in front of many problems associated nowadays with diseases' outbreaks. Algae possess a diverse metabolic system; their sterol composition is interesting due to the fact that they show in their composition unconventional structural variations [15]. The main structure consist of a tetracyclic, with a fused-ring skeleton, with the presence of a hydroxyl group at the carbon 3 (head group- 3β), and biochemical modifications at the carbon C24 (in sterol side chain), besides modifications found in the tetracyclic nuclei, and also their side chain with different alkylation's

Nowadays, there are studies focusing on unconventional sterols bioactivity like the sterols isolated from *Isochrysis galbana*, being cholest-5-24-1,3-(acetyloxy)- 3β-ol, ergost-5-en-3-β-ol, and 24-oxocholesterol acetate. Other study identified unconventional sterols in *Sargassum fusiforme:* saringosterol, 24-hydroperoxy-24-vinyl-cholesterol, 29-hydroperoxy-stigmasta-5,24 (28)-dien-3β-ol, 24-methylenecholesterol, 24-keto-cholesterol, and 5α, 8α-epidioxyergosta-6,22-dien-3β-ol all

Industrial initiative for algae biomass application started in 20 centuries with the investment in many programs for algae research. The principal countries producing algae biomass and their products are shown in the **Figure 1**. Their major focus are on biofuels, or commercializing the biomass powder, and in terms of fine-chemicals the market is based on pigments, being only two sterols commercially produced from algae, fucosterol and desmosterol [17]. With this in mind, is important highlight that sterols are important bioactive metabolites that are normally isolated from non-renewable source, comprehend the metabolic sterols pathways and the ways to modify their production, presenting algae as a new source of sterols to the world,

#### *Sterols Biosynthesis in Algae DOI: http://dx.doi.org/10.5772/intechopen.96719*

*Bioactive Compounds - Biosynthesis, Characterization and Applications*

The literature brings information's about diverse algae sterolomic profile, so in this chapter let us begin with the most curious and strong algae, considered the earliest life forms in the world, the prokaryotes microalgae (cyanobacteria). These strains are also known as blue-green algae, they are widely distributed in the world, due to their robustness. Cyanobacteria are considered by biologists a variation from bacteria and eucaryotic strains, which could lead in a production of sterols related

Cyanobacteria for this reason, can occur in marine environments with a huge salt variation, in cold waters as Antarctic system, and hot waters, could also proliferate in desert sand and rocks, providing a major response from their metabolic systems modifications according to the natural evolution. These cyanobacteria can produce different metabolites according to the habitat that they are living, for this reason, merging the information's we can understand that they can present many metabolic pathways leading to different end-sterols products. Their resistance comes from their plasmatic membrane associated mostly with structures named hopanoids, that are very similar to sterols, and are responsible for the flexibility of

The major discussion on the literature is the unknown ability of these organisms producing sterols. Many years ago, some researches described the possibility to exist only hopanoids in their structure, in fact, with the advance in tandem mass spectrometry, nuclear magnetic resonance analysis associated with new extraction techniques it was discovered the presence of sterols in their membrane. Thus, metabolism involved in sterols biosynthesis by cyanobacteria are not totally elucidated.

In the history context, the first works showing sterols production in cyanobacteria were in a filamentous cyanobacteria named as *Phormidium luridum* in 1968 [5], in this study it was isolated unsaturated sterols, like as 24 ethyl sterols, following this research's other studies investigated a way to produce this metabolite in large scale, considering the fact that this cyanobacterium has resistance in front of other microorganisms, inferring a remarkable capability for industrial application. In the ninety's the researchers Sallal, Nimer, and Radwan [6] studied other cyanobacteria strains, and verified that after dark incubation, sterols concentration increased. In in agreement to this study, Fagundes et al. [7] showed higher concentrations of sterols (β-sitosterol, stigmasterol, and cholesterol), for *Phormidium autumnale* cultured in heterotrophic system, being the inoculum without the presence of these compounds. In general, cyanobacteria are manly photosynthetic, but some strains can growth in heterotrophic conditions, in this context, it can be concluded that more studies on this particular area are necessary for further acquire

Eukaryotic microalgae are reported in the literature as the most prominent strains

for sterols production, and they are important to make feasible membrane cell permeability, and maintain structural protection [8, 9]. In this sense, the study of sterols biosynthesis started in eukaryotic cells, standing out in numerous hypothesis, and one of them is related to life adaptation on earth, showing that these molecules were produced in this cell as a protective response to reactive species of oxygen [10]. The first study in eukaryotic microalgae was in 1960 with *Scenedesmus*, showing as the major compound chondrillasterol [11], years later the same researchers Iwata and Sakurai [12] reported ergosterol as the most abundant sterol for C*hlorella.* In terms of macroalgae, the (brown) species *Ulva lactuca*, and *Cytoceira adriatica* from Adriatic Sea, were analyzed by the authors Kapetanovic et al. [13], showing that these species

**2. Algae metabolism: sterols discovery**

with vegetal, and also animal kingdom [3].

cyanobacteria cellular membrane [4].

more comprehension for biotechnological application.

were the main sterols cholesterol and fucosterol for both algae.

**142**

In summary algae strain choice directly reflects in their potential for commercial application, for this reason, the knowledge of algal productivity, and the biotechnological treatment applied for each alga is important. So, understand the metabolic pathways for the full comprehension of sterols, and their intermediary metabolites formed provides important information for future culture modifications enhancing specific compounds [14]. For this, depending on the triterpenoid produced they can be applied for medical proposes, which is a great alternative since in the last decade we have the challenge for the isolation of new compounds, in front of many problems associated nowadays with diseases' outbreaks. Algae possess a diverse metabolic system; their sterol composition is interesting due to the fact that they show in their composition unconventional structural variations [15]. The main structure consist of a tetracyclic, with a fused-ring skeleton, with the presence of a hydroxyl group at the carbon 3 (head group- 3β), and biochemical modifications at the carbon C24 (in sterol side chain), besides modifications found in the tetracyclic nuclei, and also their side chain with different alkylation's patterns [15].

Nowadays, there are studies focusing on unconventional sterols bioactivity like the sterols isolated from *Isochrysis galbana*, being cholest-5-24-1,3-(acetyloxy)- 3β-ol, ergost-5-en-3-β-ol, and 24-oxocholesterol acetate. Other study identified unconventional sterols in *Sargassum fusiforme:* saringosterol, 24-hydroperoxy-24-vinyl-cholesterol, 29-hydroperoxy-stigmasta-5,24 (28)-dien-3β-ol, 24-methylenecholesterol, 24-keto-cholesterol, and 5α, 8α-epidioxyergosta-6,22-dien-3β-ol all associated with anti-atherosclerotic function [16].

Industrial initiative for algae biomass application started in 20 centuries with the investment in many programs for algae research. The principal countries producing algae biomass and their products are shown in the **Figure 1**. Their major focus are on biofuels, or commercializing the biomass powder, and in terms of fine-chemicals the market is based on pigments, being only two sterols commercially produced from algae, fucosterol and desmosterol [17]. With this in mind, is important highlight that sterols are important bioactive metabolites that are normally isolated from non-renewable source, comprehend the metabolic sterols pathways and the ways to modify their production, presenting algae as a new source of sterols to the world, could lead to a sustainable sterols production.

#### **Figure 1.**

*Principal countries with important algae biotechnology companies' and their products. DHA docosahexaenoic acid.*
