Nutraceuticals from microalgae: Many achievements ... but challenges remain

© iStock/ Toa55

In this special edition, NutraIngredients looks at some areas where large-scale commercial production of algal sourced nutraceuticals has already been achieved - including omega-3 oils and alginate.

We also outline some of the barriers to achieving scalability in others areas, such as carotenoids, before briefly examining some of the new developments in yield improvement, which may accelerate economic viability of these compounds.

Long Chain PUFAS

Sustainability concerns regarding global fish stocks, together with ever-growing demand from the aquaculture industry have been key factors in driving the demand for alternative sources of the long chain polyunsaturated fatty acids (LC-PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).

Microalgae are the prime source of LC-PUFAs for fish and other organisms. Fish oils are abundant in both EPA and DHA because they reflect the trophic integration of diatom and flagellate type algae, which are rich in EPA and DHA respectively.

Early production of algal sourced LC-PUFAs involved predominantly DHA. The principal species used were from either fermentation of Schizochytrium sp. or the heterotrophic Crypthecodinium cohnii. Other DHA-rich species include Thraustochytrium  aggregatum and Ulkenia sp.

Martek Biosciences (acquired by Royal DSM NV in 2011) developed commercial edible DHA from both the main algal sources mentioned above. One of Martek’s proprietary products was demonstrated to have similar nutritional properties to cooked salmon. The company’s DHASCO product, derived from C. cohnii, has a DHA content of over 40% and its safety and bioaccessibility has enabled its use in infant formula, baby foods, dietary supplements and pharmaceuticals.

DSM has also succeeded in producing an algal oil (Life’s Omega) derived from a strain of Schizochytrium which has a DHA/ EPA ratio of around 2:1.

EPA

EPA-rich varieties include Phaeodactylum tricornutum, Nannochloropsis sp. and Monodus subterraneus.

The former is a diatom which naturally contains around 30-40% EPA and is considered a viable source for scalable industrial production.  Nannochloropsis’ EPAcontent is also potentially high, although very dependent upon culturing conditions, while the light-dependency of the phototrophic Monodus subterraneus to achieve high EPA yield renders commercial development problematic.

Commercial barriers

The main barriers to the commercial EPA exploitation of microalgae have been the high cost of producing biomass plus the efficient extraction of valuable products.

“The primary barrier has been stable production of EPA rich Nannochloropsis biomass at large scale (over 10 acres).  For the last two years, we have focused on the use of agronomic practices such as crop protection and integrated pest management practices, fertilizer management, and water use as well as technology improvement, to stabilize and scale our open pond production.  In addition, we have been working with technology partners to find more energy efficient, more sustainable harvesting and cultivation methods, including looking outside the algae industry for inspiration and innovation.  This is what has allowed us to expand both at our Texas facility and in the partnership with Green Stream,” commented Rebecca White, Vice President of operations at Qualitas Health, the Texas-based market leader in algal EPA production. 

Heterotrophic production, which uses a variety of carbon sources, is also an area of focus. The technique has enabled a 2-3 fold increase in LC-PUFA productivity versus autotrophic cultivation.

Recent studies have focused on optimising production parameters to maximise yields. Key input variables are not only the different algae species themselves but also carbon source (and its concentration), culture temperature and culture mode (e.g. batch, fed-batch, etc.)

Optimising the production environment has also been combined with another key development, the metabolic engineering of particularly algae strains to vary the ratio of DHA/ EPA.

“Metabolic engineering means genetically engineering organisms to directly modulate (create, increase or optimize) expression of desired metabolites or to improve cellular processes,” explained White.   

A recent example is the metabolic engineering of P. tricornutum, a species which naturally produces almost exclusively EPA, and only trace amounts of DHA. By injecting two additional genes, a strain of Ostreococcus tauri, which overexpresses delta-5 (Δ-5) saturase, and a glucose transporter gene, researchers have been able to produce a transgenic alga that produces substantial amounts of both DHA and EPA.

The research also identified that the light dependency of Δ-5 elongation and Δ-4 desaturation steps in LC-PUFA synthesis appear to be species dependent. Whereas P. tricornutum’ s DHA production capability is reduced in low light, the above elongation and desaturation processes are most active in Pavlova lutheri in darkness. Scientists are therefore examining ways to metabolically engineer a strain of P. tricornutum which is unaffected by light in its ability to generate DHA.

Despite promising results in small-scale production, commercial viability of larger production volumes using these new techniques remains some time away.

Nevertheless, prospects for the future of algal-derived omega-3 market remain bullish, according to Miguel Calatayud, CEO of Qualitas Health.

"Omega-3 is an essential nutrient that represents an exciting market, currently dominated by fish and krill. As the demand for omega-3 supplements continues to grow, people are starting to look for viable and sustainable alternatives to fish and krill oil. Most people don't know that fish and krill get their omega-3s EPA and DHA from algae," he concluded.

Alginate

Alginate (or alginic acid) is an anionic polysaccharide. It is the principal constituent in brown algae, accounting for up to 40% of its dry mass. Commercial extraction of alginate is typically from Laminaria sp,  Macrocystis pyrifera, or Ascophyllum nodosum. It is commonly used as a thickening or gelling agent in foods, drinks and cosmetics and pharmaceuticals (including Gaviscon).

Early research also suggested that alginates might facilitate metal chelation, decrease cholesterol uptake, modify gut bacteria composition and generate short-chain fatty acids.

Dietary alginates have also been incorporated into slimming aids due to their satiety inducing properties.

Recently, Kerschenmeyer et al  identified the ability of sulphated alginate molecules to reduce oxidative stress in vitro. The cell study also identified an anti-inflammatory effect in human chondrocytes and down-regulation of gene expression and synthesis of a pro-inflammatory cytokine in macrophages. The strength of these effects increased as the researchers raised the degree of sulphation   in the modified alginate molecule. Study results suggest that sulphated alginate may prove to be a promising biomaterial for osteoarthritis treatment.

Astaxanthin

Astaxanthin is a carotenoid that falls within the class of compounds known as terpenes. The predominant marine source of this brightly coloured, fat-soluble pigment is the microalgae species Haematococcus pluvialis although it is also found in Chlorella zofingensis. The astaxanthin content of H. pluvialis is around 1.5 -3% of its dry mass in its initial ‘green’ form.

Rapid astaxanthin accumulation occurs through spore formation under unfavourable environmental conditions, including low nutrient availability. Thus, astaxanthin content in the secondary ‘red’ cultivation stage is an order of magnitude higher.

Astaxanthin is used in the nutraceuticals, cosmetics, food and aquaculture sectors. In the nutraceuticals industry, it is recognised as a “super anti-oxidant” with numerous applications and many potential health benefits.

Properties include anti-inflammatory, anti-ulcerative, immunomodulatory, cardioprotective, photoprotective, and chemoprotective. Astaxanthin can also cross the mammalian blood-brain barrier, therefore it may be effective in neurological disease such as Alzheimer’s.

The majority of evidence to-date has involved in vitro and animals studies although some human data exists in a more limited set of outcomes.

Due to its lower production cost and ease of scalability, in 2016 synthetic astaxanthin represented around 99% of global production of the carotenoid. However, the antioxidative properties of the synthetic version are considerably weaker than natural algal-derived astaxanthin.  This may be due to the algal-sourced product being 95% esterified (versus free-form in the synthetic source).

Numerous barriers to large-scale commercial production exist. These include low cell densities and biomass productivity; inefficient and cost ineffective cultivation, drying and extraction technologies; and inadequate contaminant, parasite and predator control.

Major players in the algal derived astaxanthin industry include Cyanotech Corporation, Valensa International, Algatechnologies, Fuji Chemical Industry Co, BGG, Algaetech International and Parry Nutraceuticals.

Due to the vast difference in selling price between natural and synthetic versions of astaxanthin, the industry producers group Natural Algae Astaxanthin Association (NAXA) has established a verification program to confirm the authenticity of product derived from H. pluvialis. It is hoped that the program will reduce the potential threat from any attempt to pass off synthetic astaxanthin as ’natural’.

Lutein

Lutein is a member of the xanthophyll family of carotenoids. Its characteristic yellow pigment is used for food, drug, cosmetics and animal tissue colouration. Lutein is also a major constituent in the macular pigment of the retina. Humans are dependent upon dietary sources, as they cannot synthesise lutein themselves.

Lutein is therefore a key nutraceutical in eye health, in particular preventing and slowing the progression of age-related macular degeneration (AMD), but also reducing risk of cataracts.  Its antioxidant radical-scavenging properties may also provide cardiovascular and chemoprotective benefits.

The principal source of lutein is currently from marigold flowers. However, microalgae is also a source of the carotenoid, albeit it in limited quantities.

The genera Chlorella sp (particularly C. zofingiensis), Scenedesmus spand Muriellopsis sphave commercial production potential, if economic constraints can be overcome. In particular, heterotrophically cultivated Chlorella accumulates high lutein content.

Chlorella supplements themselves have previously been demonstrated to raise serum lutein content in a Korean study previously reported by Nutraingredients.

Microalgae have a higher growth rate than marigold, do not compete for land resources and have a lower water demand. Furthermore, algae biomasses can be harvested all year.

Nevertheless, at present there is no commercial scale production of lutein. Barriers to commercial viability include low lutein content of the microalgae, high harvesting cost, and the high energy demand in the cell disruption and extraction steps of the process.

However, economic feasibility might be improved if the microalgae derived lutein production facility were to be linked to a CO2 emission abatement project.

Zeaxanthin

Similar to lutein, zeaxanthanin is a yellow-pigmented xanthophyll carotenoid. Its uses as a neutraceutical are again similar to lutein. Zeaxthanin is also present in the macular region of the retina and its photoprotective benefits are widely recognised as effective in preventing AMD and cataracts.

Microalgae with commercial production potential include Dunaliella sp (especially D. salina and D. tertiolecta), Microcystis aeruginosa and Nannochloropsis.

Dunaliella species have been the principal source due to their ability to accumulate carotenoids in high-salinity conditions, avoiding competition for freshwater resources. The lack of rigid cell wall in this species facilitates the zeaxanthin extraction process.

Again, no commercial production of zeaxthanin exists. However, recent research has made progress in improving zeaxthanin yield of D. tertiolecta by around 10-15% through chemical mutagenesis with ethyl methanesulphonate (EMS). Optimal productivity was also found at a salinity very close to that of seawater, suggesting this cultivation medium might be feasible as a means of improving economics versus freshwater.

Despite technological advances in yield optimisation and cultivation techniques, the establishment of large-scale commercially viable production of the two carotenoids lutein and zeaxanthin remains elusive.

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