nergy and food. These are the building blocks of any ecosystem. They are also the most important material components of any human society. The causes of wars, the motivation for inventions, the history of humankind itself is a struggle to find and secure these two resources. But a billion-year old group of microbes has the potential to provide us with food supplements, chemical feedstock and biofuels.
Photosynthetic microbes are a heterogeneous group of bacteria and eukaryotes that live on oxygenic photosynthesis. These green bugs have left their imprint on the planet long before the first multicellular organism appeared. Around 1.5 billion years ago, the early cyanobacteria enriched the Earth’s atmosphere with oxygen. The petroleum we use is algae and other plankton undergone millions of years of high temperatures and pressure.
Algae and cyanobacteria can grow biomass literally out of thin air. They have a remarkable biosynthetic potential. They can be used for synthetic biology applications. They can be turned into carbon fiber. The European Commission considers green microbes as an excellent food source. They can survive almost every imaginable ecosystem, even the outer space! Consequently, they can grow in areas not used for agriculture, in harsh environments, with minimal oversight.
However, the use of photosynthetic microbes in the biotech industry is limited at best. The organisms of choice are heterotrophic bacteria and yeasts for biomanufacturing, and of course crop plants as our major food source. But what are the reasons of this apparent oversight?
Lack of basic knowledge and expertise
In terms of complexity, algae are defined by their photosynthetic machinery. Cyanobacteria have larger genomes than the average bacteria, and more subcellular compartments (such as thylakoids to accommodate the photosystems and carboxysomes to concentrate CO2. Eukaryotic algae have chloroplasts, compartments dedicated to photosynthesis. Photosynthetic microbes have evolved to make the best use of sunlight when available. These lifestyle choices set them apart from model heterotrophs, as well as photosynthetic land plants. And these differences require dedicated research on algae to understand them and better manipulate them for industrial applications.
Our knowledge about algae and cyanobacteria is lagging behind when compared to other microbes, plants and mammals. Their metabolism is not well studied, their response to environmental cues remains obscure, and their environmental diversity is unexplored. There are very few research labs dedicated on the biology and biotechnology of photosynthetic microbes. As a consequence, there are fewer tools, less expertise, and less familiarity with them. Their metabolism and regulation mechanisms are not fully known. This translates to reluctance for entrepreneurs to invest in algal applications. The attitudes are changing, and photosynthetic microbes become more popular both for basic and applied research studies. But the knowledge gap remains to be filled.
Slow growth and low cell densities
Escherichia coli, the molecular biology workhorse, duplicates every 45 minutes. Vibrio natriegens, the fastest growing bacterium, every 10 minutes. Synechocystis, a model cyanobacterium doubles every 6-18 hours, while the fastest cyanobacterium reported has a generation time of two hours. In simple words, this means that a culture of bacteria will reach its maximum biomass over a few hours, while an algal one will need several days.
A second related problem is the low cell density that photosynthetic microbes can reach in a liquid culture. The cells need ample sunlight to grow. As a result, they stop growing at night or in overcast weather. As the algae multiply, they start shading each other, making sunlight harder to penetrate. This crowding reduces the growth rate (even more) and limits the maximum biomass they can produce in a given culture volume.
Algae need specific bioreactors that differ from the typical fermentation tanks. Glass or plastic tubes, transparent bags, or raceway ponds are some of the growth facilities in use. But the development of an ideal cultivation system is yet to be achieved.
In the beginning of 2010s, the idea of algae-based biofuels was prominent and attracted significant investments. But a few years ago, the industry received a significant blow. Several biofuel companies went bankrupt amid fraud allegations. Sapphire Energy, an algae company that had attracted significant investment and backing by the Department of Energy, stopped its operations and was sold in 2017. The company didn’t manage to reach its targets for yields and price for the crude oil they had developed.
Despite any technological shortcomings, the biofuel companies could not match the drop in the oil prices that happened at that time. And the market reaction to the yeast-made artemisinin teaches an important lesson: current suppliers will respond by dropping the prices, even below profit, to prevent the establishment of new players. All novel applications are vulnerable to such practices, but algae and cyanobacterial biotechnology even more so. And the bad biofuel experience fuels the reluctance for private and public investments in the field. As the technology needed for profitable operations is not yet mature, cyanobacterial and algal biotech would require significant support.
Need for different business model
Photosynthetic microbes will not replace bacteria and yeast in fermentation processes. They can’t and shouldn’t compete in situations where they have no clear competitive advantage. On the contrary, they should act complementarily by expanding the application space. Algae and cyanobacteria do not need sugar and nutrients that could otherwise feed the population. They capture carbon dioxide and can grow in areas not suitable for agriculture. They can produce high quantities of metabolites difficult to make in other organisms, such as carotenoids, ω-3 fatty acids, and complex plant natural products.
The successful use of photosynthetic microbes needs different business models and unique niche areas. They are already strong in the market as food supplements (see Chlorella and spirulina), and they have a strong biotech potential. We can’t afford to let it go to waste!
Kostas Vavitsas, PhD, is a Senior Research Associate at the University of Athens, Greece. He is also community editor for PLOS Synbio and steering committee member of EUSynBioS. Follow him on Twitter @konvavitsas