While ultimately the hard physical metrics for microalgal biocrude are essentially the energy returned on investment (EROI) and the economic viability, the maturing and scaling of the technology still require further development. During this early development phase, commercial viability requires a profitable path to technology deployment. Several approaches are possible for dealing with this problem.

High Value Products and Services (HVP&S) Algal GM is in its infancy compared to other systems. A challenge of generating GM strains for HVP&S production is to provide useful products and services that cannot be easily generated in more mature technologies. There is no rational point to replicating in algae a service that can be easily and economically performed by yeast or E. coli aside from reasons such as marketing appeal. The relative advantages of algae as GMO vehicles must therefore be carefully considered on a case by case basis. Recombinant products such as peptides larger than those able to be chemically synthesised, but small enough to be extracted with relatively harsh techniques, may be particularly suitable. Many HVP&S GM strains will be designed to operate under heterotrophic conditions which simplify reactor design.

The difference between these approaches is that modification of bulk mass and energy flows is focussed on energy production and is strictly limited by the ther­modynamics of light harvesting and carbon fixation, whereas HVP&S approaches are less thermodynamically constrained (and indeed, may not even utilise photo­autotrophic systems) but are focussed mainly on economic gains.

Enabling and Supportive Technologies Given the constraints outlined above, it is clear that GM strains for HVP&S and those for biofuels applications will have little in common and it is unlikely that a single strain (or industrial facility) will serve both purposes, which argues against the ‘biorefinery’ concept if it is confined to a single strain or process. Nonetheless, the common biology underpinning all algal systems means that most of the enabling technologies invented in this space will apply similarly to a multitude of different algal biotechnology systems, yielding substantial cross-fertilisation. It is here that the biorefinery concept may be most profitable.

Many supportive technologies will therefore need to be developed before the industry matures, and GM can make major contributions to these. Protein and lipid export systems, for example, may reduce internal product inhibition while reducing harvest costs; modified photosynthetic systems may improve the efficiency of utilisation of incident light; and fluorescent signals may be generated to monitor internal biochemical processes. None of these technologies would intrinsically compromise the ability to convert light to fuel, but might greatly simplify or reduce costs for other biotechnological aspects. Clearly, there is a vast creative space for innovative GM approaches in this area. To the extent that such technologies reduce energy wastage during production, they can improve the EROI even without an alteration of the fundamental light-harvesting efficiency.

Advantages of Algae as Heterologous Expression Systems Algae as heterologous expression systems are comparable to plant systems primarily for their ability to produce proteins with post-translational modifications. They may not replace the established and commercialised bacterial and mammalian expression systems but offer the potential for biological products which are difficult to produce in an active form in prokaryotic systems and are expensive to make in eukaryotic systems (e. g. antibodies). They also offer advantages over conventional systems to be chosen for new products which cannot be produced in other systems [e. g. anti-cancer toxin (Tran et al. 2013)] and therefore provide a valuable opportunity for the industry.

One advantage that can make transgenic microalgae systems competitive in the field of pharmaceutical proteins is that many algae lack endotoxins or human pathogens (Mayfield and Franklin 2005; Walker et al. 2005) and are therefore ‘Generally Recognized As Safe’ (GRAS). This could allow for a reduction of necessary purification steps during downstream processes as well as simplify quality control and therewith allay production costs. Another advantage of algae compared to higher plants is vegetative reproduction, leading to uniform clones with comparable production rates. This relates to product quality, e. g. demonstrated as certain beneficial post-translational modifications, product stability or biosafety. Microalgae systems display high growth rates and need only a short time from transformation to product formation so that scale up could be implemented within a few weeks within commercial processes. The cultivation can be inexpensive due to the relatively low costs of typical mineral media needed, therefore supplying a large-scale robust growing system which can yield cheaply extractable high-volume production. This provides possible cost savings during production processes, which could play a role in special fields, where large quantities of products are required at low costs such as recombinant antibodies or veterinary products.

Microalgae have already been established as biotechnological production sys­tems and approved by the US Food and Drug Administration for a number of secondary metabolites useful as food additives or cosmetics (Administration 2003, 2004, 2010a, b, 2011, 2012; Plaza et al. 2009) and for the production of carotene using Dunaliella salina (Hosseini Tafreshi and Shariati 2009) and lutein as an antioxidant and food colourant. Antiviral activities have been shown. Vaccination concepts for a large number of diseases prevalent in developing nations based on recombinant antigen expression in microalgae could result in inexpensive pro­duction and distribution as well as long-term storage at room temperature (Dreesen et al. 2010; Specht et al. 2010). Edible vaccines are a possible field of application for algal expression systems, combining biosafety issues with inexpensive pro­duction and storage and therefore opening up making products accessible for less developed countries (Gregory et al. 2013). In the context of regulatory aspects in the pharmaceutical sector, novel expression systems have to offer enormous advantages over conventional systems to be chosen for new products. The possi­bility to use a closed photobioreactor system contributes to reducing the risk of contamination and prevents transgenes dispersing into the environment.