Harnessing The Elements To Feed Microbes

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The vast majority of fuels and chemicals used by humans are made from fossil carbon. Bioproduction from microorganisms, such as bacteria or yeast, might provide a way to wean us from our dependence on these unsustainable sources. In fact, microbes are already cultured at a huge scale across the planet – think breweries – and have been handled and processed by experts for centuries. Yet, in order to grow and produce a chemical of interest, microbes must be supplied with a suitable feedstock. What can we afford to feed them?

In recent years, the use of sugars as feedstock in biofactories has dramatically expanded. However, as the use of sugars for bioproduction increases, we begin to witness its drawbacks. First, sugar used by microbial biofactories cannot be used for food or feed. As our nutritional requirements continue to expand, diverting agricultural resources towards bioproduction become less sustainable and could severely decrease food security. Moreover, expanding agricultural land use for the sake of bioproduction reduces natural habitats and biodiversity and burdens the environment.

Alternative feedstocks, which do not compete with agricultural production, have been suggested, for example, lignocellulosic and algal biomass. However, the processing of these feedstocks is very challenging, necessitating costly and inefficient conversion methods. Even more important, the efficiency by which plants and algae intercept light and convert it into to biomass is very low, casting doubt on the very basic idea of harnessing this natural process to feed microbial bioproduction.

So what is the alternative? An ideal microbial feedstock would be directly derived from almost unlimited resources, fully available in the environment. To put it more poetically, we want to derive bioproduction from the “elements” of nature: air – from which we take carbon dioxide as a direct carbon source; water – which supplies the hydrogen equivalent; fire – the renewable energy, e.g., solar and wind, that provides the necessary driving force; and earth – representing the minerals, i.e., other elements, that are needed for microbial growth.

How do we feed these “elements” to microbes? In a recent paper, we investigated and compared different approaches to provide microbes with the carbon and energy they need for growth. From a point of view of energy, electricity provides a great starting point. While solar energy can be directly used to energize chemical processes, its conversion to electricity provides highly-needed flexibility. That is, when the sun doesn’t shine, the wind blows to drive turbines. If both are not available, hydro- or geo-energy could come to the rescue. Hence, by tapping into electricity as an energy source, we tap into a myriad of different renewable sources without being completely dependent on any.

Electricity can be used to transfer hydrogen equivalent from water to a chemical carrier. Microbes can then take the hydrogen equivalent from the carrier and use it to convert carbon dioxide into biomass and products. Several inorganic compounds, such as ions of iron or nitrate, can serve as such carriers. An even better approach is to use electricity to transfer hydrogen equivalent from water directly into carbon dioxide. The resulting reduced organic compound can be used as a microbial feedstock, “carrying” with it three of the required elements: carbon, hydrogen equivalent, and energy.

In our analysis, we show that carbon monoxide and formic acid, both one-carbon molecules, can serve as ideal intermediates between the former, chemical process, and the latter, biological conversion. However, while carbon monoxide is a toxic, flammable gas with low solubility, formic acid is completely soluble and easy to handle and transport. This makes formic acid an especially promising feedstock for bioproduction. Together, we envision a production chain which harnesses the advantages of each field: physicochemical processes support fast and efficient conversions of renewable energy into electricity and of carbon dioxide into formic acid, while biological processes are effective in converting this latter simple feedstock into a wide array of complex products.

It will take some time before we can fully implement this vision. Apart from further improvements in electrochemical processes, in order for the production chain to reach its full potential, we need to design and engineer better metabolic solutions for microbial growth on formic acid. While multiple microbes can grow on formic acid as sole carbon and energy source, most of the metabolic routes they employ for this growth are either limited in efficiency or are restricted to extreme conditions.

One of the main goals of our lab is to use engineering-like tools to design and implement novel metabolic routes that would support bioconversion of formic acid at very high efficiency and under non-extreme conditions. We are specifically working on engineering model microbes, widely used in the biotechnological industry for bioproduction processes, to grow on formic acid using the most efficient pathway we have designed so far: the reductive glycine pathway. Upon completion, these engineered microbes could pave the way for sustainable bioproduction of value-added chemicals from renewably-produced formic acid, and thus transform the way we produce our everyday commodities.

These findings are described in the article entitled, Towards sustainable feedstocks: A guide to electron donors for microbial carbon fixation, recently published in the journal Current Opinion in Biotechnology.

This work was funded by the European Commision and is part of the EU consortium project called eForFuel. The work was conducted by Nico Joannes Claassens and Arren Bar-Even from the Max Planck Institute of Molecular Plant Physiology, and Irene Sánchez-Andrea and Diana Zita Sousa from Wageningen University. This research

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