What makes AlgaeCom and its objectives unique?

Microalgae have always been an exciting target for aquaculture and biotechnology, as they represent a largely untapped reservoir of novel and valuable bioactive compounds. To this end, AlgaeCom combines basic and applied research to exploit microalgae biodiversity for the development of high, added value ingredients for novel cosmeceuticals. Within the AlgaeCom team, we strongly believe that advancement of microalgae biotechnology in Europe carries significant promise for innovative, sustainable development.

Why are the pharmaceutical and cosmetic industries interested in microalgae?

Microalgae may be exploited either as natural multifunctional extracts or purified specific products, including bioactive secondary metabolites, polysaccharides and enzymes. These extracts and/or purified biomolecules have potential as strong anti-ageing, antioxidant and hydrating agents.

To what extent does the AlgaeCom team combine pure and applied research?

Although microalgae have been commercially cultivated for over 50 years, in-depth structural, molecular and physiological characterisation is now necessary to realise their full potential. Microalgae possess a high metabolic plasticity which allows them to successfully adapt and occupy a wide range of diverse environmental niches. Greater understanding of their biology and metabolism will enhance our ability to develop and optimise application-based cultivation systems for the production of custom quality biomass for specific applications.

How essential have new technologies been to AlgaeCom’s success?

New and emerging technologies play a central role both in our research and industrial

production processes. In AlgaeCom, we are using -omics technologies and platforms for screening and characterising marine and freshwater microalgae biodiversity, developing genomics, catalomics, metabolomics and glycomics resources for selected microalgae species and carrying out in vitro functional characterisation of microalgae cosmeceuticals. We are also applying new ideas and technologies for developing and optimising application-based microalgae culture systems at different scales, and creating analytical molecular diagnostic tools for real-time microalgae metabolism monitoring.

How does AlgaeCom coordinate its international partners?

Close interaction, communication and transfer of knowledge is extremely important for the success of AlgaeCom. The whole consortium is structured around this priority because we have two industrial partners: one responsible for the production of microalgae biomass, and the other for its incorporation in novel cosmeceuticals. There are also two academic partners contributing their respective research expertise. For this interaction to be successful, we are implementing a demanding transfer of knowledge and scientific collaboration plan, based on recruitment of new scientists, researcher secondments between academic and industrial partners, shared experiments, annual workshops and meetings.

As AlgaeCom Coordinator, I would like to acknowledge and thank all the scientists and personnel from the participating organisations for the exciting opportunity to work in this highly productive and stimulating environment. At the same time, as representative of the whole consortium, I would like to express our thanks to the People Programme (Marie Curie Actions) of the EU’s Seventh Framework Programme (FP7) for the financial support that has enabled us to materialise our ideas.

Could you elaborate on the steps you take to exploit microalgae biodiversity?

The work pipeline starts with screening and characterising lab-scale microalgae cultures. Our industrial partner Fitoplancton Marino is responsible for isolating and maintaining various microalgae species, and assaying different strategies of microalgae culture and harvest in order to increase productivity and activity of selected metabolites and enzymes with possible interest. Our academic partners within the Agricultural University of Athens and the French National Centre for Research on Plant Macromolecules (CERMAV) are responsible for screening and analysing microalgae biomass with an emphasis on bioactive compounds of interest for the cosmetic industry, including enzymes, polysaccharides and low-molecular-weight metabolites. APIVITA, as an end-user, is responsible for the development and testing of formulations founded on these extracts and biomolecules. In parallel, bioactivity and safety of these extracts and fractions is assayed in vitro using platforms based on human skin cell cultures and skin models developed within the project.

What success has the consortium had so far?

We already have several microalgae extracts and specific biomolecules coming out of our research and development pipeline. The most promising extracts are already being incorporated by APIVITA, at the concentrations dictated by our in vitro tests, in cosmeceutical formulations. These include night and day creams, face serums and shower gels. APIVITA plans a market launch of at least one product containing microalgae extract with anti-ageing and hydrating properties by 2017.

Dr Emmanouil Flemetakis describes the groundbreaking project that is using state-of-the-art technology to develop natural constituents and cosmetic products with beneficial and anti-ageing properties

Exploiting the enormous potential of microalgae

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PHARMACOLOGY

Photos of the production facilities of APIVITA (1,2,3) and the laboratory and photobioreactors at Fitoplancton Marino premises (4,5).

The collaborative European AlgaeCom project is mining the vast, yet so far untapped, potential of microalgae extracts for new cosmetic products with promising restorative and nourishing properties

Restorative powers of microalgae

FOR THOUSANDS OF years, people have used balms, emollients and cosmetics to improve the protective qualities and appearance of the largest organ of their bodies, the skin. Use of cosmetics specifically to achieve a more youthful look, however, is relatively recent, dating from the 1900s. Today, the global anti-ageing skin care market is huge, valued at more than US $260 billion. Of that market, the share taken by cosmeceuticals that deliver highly effective and efficient active substances with anti-ageing benefits is growing rapidly at an annual rate of 8.62 per cent, and is expected to reach $57.3 billion by 2019.

The historical use of damaging ingredients, such as lead, and the dubious sustainability and ethics of certain animal and microbial ingredients, have made safety and ingredient traceability key purchasing factors for modern cosmetics consumers. Natural enzymes, amino acids and botanical extracts are perceived as preferable to oils and surfactants from large-scale engineering as, for example, in the petrochemical industry. Global demand for natural, organic ingredients in cosmetics without attributable, negative environmental impact or animal cruelty is significantly rising, supporting the philosophy of green growth and sustainable development.

TRUE ACADEMIC-INDUSTRIAL PARTNERSHIPAPIVITA, a cosmetic company based in Greece, combines naturally derived active ingredients with medicinal and aromatic plant extracts, bee products and organic essential oils to deliver beauty products that do not contain silicone, paraben, mineral oil, propylene glycol, polycyclic musk, nitromusk, phthalate – or any other ingredient associated with adverse health or environmental effects. APIVITA is one of two industrial partners in AlgaeCom, a multinational collaboration between academic researchers and industry innovators, which aims to develop novel anti-ageing and other cosmeceuticals – cosmetics with beneficial effects – from microalgae.

The other industrial partner is Fitoplancton Marino, based in southern Spain, who has expertise in high-value microalgae products and production systems. In fact, Fitoplancton Marino is the first microalgae production company to receive ISO22000 and FSSC22000 certification for microalgae production. It is also the first company to receive a novel food authorisation from the EU for a marine microalgae species, and their products are rated as ‘generally recognised as safe’ in the US.

Led by biochemist Dr Emmanouil Flemetakis and enzyme technologist Dr Nikolaos Labrou of the Agricultural University of Athens, AlgaeCom is exploring the huge value of cosmeceuticals by exploiting the diversity of microalgae in Europe. From the perspective of academic involvement in AlgaeCom, the Agricultural University of Athens is partnering with Dr William Helbert at the University of Grenoble-associated Centre for Research on Plant Macromolecules (CERMAV), part of the French National Centre for Scientific Research (CNRS), who bring expertise in biopolymers, especially polysaccharides, and application-targeted transformation of biomass; “AlgaeCom is a success story because of its multidisciplinary approach,” explains Flemetakis.

MICROALGAE PROMISESAs an abundant, renewable, natural and non-toxic alternative to fossil materials, with equivalent mechanical, thermal and optical properties, biomass is becoming increasingly attractive as a resource for new materials and products, such as biofuel. According to Flemetakis, biomass from microalgae has the potential to revolutionise biotechnology in fields beyond biofuels, as a source of novel, high added value biomolecules in such applications as healthcare, materials, cosmetics, nutraceuticals, aquaculture, pharmaceuticals and cosmeceuticals. Importantly, microalgae extracts offer the same functionality as microbial and animal-derived proteins, and enzymes needed for cosmeceuticals.

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ALGAECOM

OBJECTIVETo identify and characterise microalgae biodiversity as a source for state-of-the-art, high-value bioactive ingredients for cosmeceuticals.

KEY COLLABORATORSDr Emmanouil Flemetakis, Assistant Professor; Dr Nikolaos Labrou, Professor, Agricultural University of Athens, Greece • Dr William Helbert, Research Director, CERMAV-French National Centre for Scientific Research (CNRS), France • Dr Konstantinos Gardikis, Scientific Affairs Director, APIVITA, Greece • Ms Lalia Mantecon, R&D Manager, Fitoplancton Marino SL, Spain

PARTNERSAgricultural University of Athens

CERMAV-CNRS

APIVITA

Fitoplancton Marino

FUNDINGMarie Curie Actions

EU European Seventh Framework Programme (FP7)-PEOPLE-2011-IAPP

CONTACTDr Emmanouil Flemetakis Assistant Professor of Biochemistry

Laboratory of Molecular Biology Department of Biotechnology Agricultural University of Athens Iera Odos 75 11855, Athens Greece

T +30 210 529 4343 E mflem@aua.gr

www.algaecom.aua.gr @ApivitaSA @FitoplanctonM www.facebook.com/apivita www.facebook.com/fitoplanctonmarino www.linkedin.com/company/apivita-sa https://plus.google.com/+APIVITA/about

DR EMMANOUIL FLEMETAKIS is an assistant professor at the Agricultural University of Athens. His research expertise includes state-of-the-art gene cloning applications, -omic

technologies, tissue culture, and plant and microbe genetic transformation technologies.

Flemetakis believes that, because of the extensive coastline and easy access to diverse marine and freshwater habitats, Europe is well placed to maximise the potential of microalgae, and so remain at the forefront of biotechnology in the future: “The foundations for a thriving community are established in geographically dispersed academic centres of excellence, and a small, but growing, company base. Microalgae biotechnology could contribute to the development and revival of nearly every industry sector,” he asserts.

STREAMLINING PRODUCTIONDespite their enormous biodiversity and biotechnological potential, microalgae have received little scientific or industrial attention. Of the 30,000 strains identified so far, few have been fully analysed. Flemetakis believes this is partly due to incomplete knowledge of their biology and biochemistry, especially compared with that of other organisms. Moreover, the development of highly productive, cost-effective microalgae cultivation systems is a young area of enterprise. He points out that to release the potential of algae-based ingredients for beauty and health applications, it is necessary both to be able to manipulate their growth and target specific biomolecules to fit increasingly niche product specifications. However, each strain requires different culture conditions and systems.

Europe currently leads the world in enzyme development and production. Modern nanomaterials and encapsulation technologies are paving the way to stable protein and enzyme development systems, an example being for developing superoxide dismutase (SOD). SOD molecules are able to capture reactive oxygen species – free radicals – and so protect skin from such harms as environmental pollution, bacteria, smoke and ultraviolet rays. However, current production costs remain high, and yields and purity are low because of the inadequacies of extraction and purification technologies. Within the AlgaeCom project, significant progress has been made in the development of new purification technologies for the extraction, concentration and purification of algae cosmeceuticals and enzymes. Thus, AlgaeCom has significantly contributed to the improvement of current manufacturing technologies and associated costs by streamlining production processes to produce high-quality, low-cost cosmeceuticals from microalgae, with desirable properties matching those of compounds like SOD.

STATE-OF-THE-ART METHODOLOGYThe AlgaeCom project detects and selects marine or freshwater microalgae strains with high added-value metabolites, especially in the forms of cosmeceutical compounds and polysaccharides, for analysis. The team has developed -omics resources and analytical molecular diagnostic tools for this purpose.

Once selected, the microalgae are functionally characterised and tested for potential bioactivities in vitro using human epidermal cell lines and models of human skin in the laboratory. Application-targeted microalgae culture

systems are then developed and optimised at different scales under varying culture conditions to optimise the metabolite production rates of each strain. Trials of their growth are subsequently conducted at industrial scale in large photobioreactors, using quantitative reverse transcription polymerase chain reaction techniques to monitor their carbohydrate and polysaccharide metabolism rates in real time, to guide process adjustments and therefore maximise their biosynthesis.

New cosmetic products incorporating such elements as enzymes – lipases, proteases and anti-oxidant enzymes – small secondary metabolites and polysaccharides are then designed, formulated and evaluated against skin models in vitro.

FUTURE BIOTECHNOLOGYThe AlgaeCom experience strongly indicates that complementary approaches are needed if exploitation of the huge biodiversity of microalgae as a source for novel cosmeceuticals is to be successful in the future, though he acknowledges that the challenge is formidable.

The AlgaeCom team is to present the results of one of their investigations at the 9th European Conference on Marine Natural Products at the University of Strathclyde in Glasgow, UK, later this year. The investigation into the effect of microalga Nannochloropsis gaditana (NannoG) extract on primary normal human dermal fibroblasts subjected to in vitro oxidative stress showed that NannoG increased anti-ageing, hydration and antioxidant responses by affecting transcript levels of related human genes and manipulating the action of specific enzymes that control skin ageing, wrinkles and skin-texture: “Our results contribute to the emerging picture of microalgae at the centre of future biotechnology,” observes Flemetakis. “Our in vitro bioactivity assays demonstrate that, compared with other natural cosmeceuticals, microalgae extracts and biomolecules demonstrate equal, or even superior, beneficial and protective properties. The time to invest in the underpinning science, knowledge networks and understanding of this major field has arrived.”

AlgaeCom has significantly contributed to the improvement of current manufacturing technologies and associated costs by streamlining production processes to produce high-quality, low-cost cosmeceuticals from microalgae

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