Future innovation is key – microbial pathways

To be able to make an impact on the carbon balance and mitigate the atmospheric CO2 levels, two important questions need to be addressed: (i) Which products can we produce from C1 substrates that significantly reduce the carbon footprint, and (ii) which production cycles need to be implemented to realize a C1-based bioeconomy for the future? In the following sections, we give an overview of C1-assimilation pathways that are exploited and compare their thermodynamic efficiencies as well as their energy demand in the form of ATP and NAD(P)H. Further, we provide an opinion on how C1 substrates can be implemented for energy, material, and food production in the future.

C1-assimilation pathways

Nature offers a great diversity of carbon utilization pathways and so far, seven natural autotrophic carbon-fixation pathways have been characterized. Those include the Calvin-Benson-Bassham (CBB) cycle, the reductive tricarboxylic acid cycle (rTCA), the oxygen-sensitive Wood-Ljungdahl pathway, the 3-hydroxypropionate (3-HP), the hydroxypropionate/4-hydroxybutyrate (HP/HB), and the dicarboxylate/4-hydroxybutyrate (DC/HB) cycles, and the reductive glycine pathway. These are reviewed and compared extensively elsewhere19,20,21.

The first step towards a C1-based bioprocess is to select or design an effective microbial pathway for carbon fixation (Fig. 1). Several options exist depending on the used microbial platform, the product of interest, and the parameters of cultivation. In general, autotrophic microorganisms would be an obvious choice for a C1-based production platform as they can grow solely on CO2 and an energy source (either from light or chemical reactions)19. The CBB cycle is the most abundant pathway to fix CO2, used by photoautotrophs and some chemoautotrophs, whereby the latter employ more efficient pathways for energy generation22. However, due to their complex nutrient requirements, process demands and difficulties in genome editing, the use of chemoautotrophs is still limited in industrial applications23. Phototrophic microorganisms, such as cyanobacteria and eukaryotic microalgae are easier to cultivate and many studies have focused on their utilization in the biotech sector6,24,25. Nevertheless, the industrial scale of production is still challenged by technical hurdles in photobioreactors including the light availability, effective distribution, and optimization of wavelength and intensity22.