Life in a carbon dioxide world

Few chemicals have hit the headlines so widely that everyone knows their formula, but carbon dioxide is an exception. It is so crucial for understanding climate change that we recognize its shorthand name of CO2 as a threat to our future. For most microbes, however, CO2 looks more like a feast than a threat. Microbes have tools at their disposal — CO2-fixation pathways — that enable them to incorporate CO2 into their cell mass. These pathways are essential for life because all ecosystems on Earth ultimately depend on cells that make organic material from CO2. Writing in Nature, Steffens et al.1 uncover key details about an ingenious pathway that enables bacteria to thrive in a hydrothermal environment surrounded by gases consisting mainly of CO2.

Steffens and colleagues studied Hippea maritima bacteria. These microorganisms shun oxygen, love temperatures near 60 °C, and obtain energy from the reaction of hydrogen gas (H2) with sulfur to make hydrogen sulfide (H2S). As with all life forms, they need a carbon source to grow. And, like many, they can choose this source depending on what is available in their environment. If a rich diet of protein is on offer, H. maritima incorporate this as a building block into their metabolic pathways for growth.

But if H. maritima grow in the presence of CO2 concentrations of 40% (1,000 times higher than atmospheric CO2 levels), they do some ‘chemical engineering’, using a pathway called the reversed oxidative tricarboxylic acid cycle. That might sound complicated, but it is connected to something familiar — human nutrition. After the food we eat is broken down in the gut, our cells convert the sugars, fats and proteins contained in the food into energy and CO2 using a pathway called the tricarboxylic acid (TCA) cycle. This is also called the Krebs cycle, after the scientist who discovered it2. The TCA cycle is used by nearly all life forms, but it can run backwards in some bacteria3: this change of direction, to give the reversed oxidative TCA cycle (Fig. 1), invests energy that converts CO2 into amino acids, sugars and lipids.

Figure 1

Figure 1 | The reversed oxidative tricarboxylic acid (TCA) cycle. Almost all life forms use the TCA cycle to convert molecules such as amino acids, sugars and lipids into energy and carbon dioxide by means of a pathway that involves molecules such as pyruvate, oxaloacetate, 2-oxoglutarate, citrate and acetyl coenzyme A (acetyl-CoA). Some bacteria can run this cycle in the reverse direction (it’s then called the reversed oxidative TCA cycle), incorporating CO2 and hydrogen (H2) to form molecules such as amino acids, sugars and lipids. Steffens et al.1 used approaches such as tracking labelled carbon atoms to reveal the mechanism that enables the bacterium Hippea maritima to run the TCA cycle backwards. The authors report that a high level of the enzyme citrate synthase is key to pathway reversal.

What enables the TCA cycle to run in reverse under specific growth conditions has been a mystery, until now. Steffens et al. show that H. maritima’s secret trick is to adjust levels of a crucial enzyme in an unexpected way, so as to be ready to assimilate high concentrations of CO2 before they are encountered. This generates an elegant harmony between the microbe’s environment and its metabolism.

H. maritima uses the reversed oxidative TCA cycle when high levels of CO2 are present, and this is where the technical brilliance of Steffens and colleagues’ investigation becomes evident. The authors fed the bacteria amino acids and CO2 labelled with the 13C isotope of carbon. Both of these food sources were channelled into the reversed oxidative TCA cycle. Tracking 13C accumulation in the intermediate molecules of this pathway in growing cells enabled the authors to uncover which carbon source the cells used down which route of the pathway. It also enabled them to determine how many full ‘turns’ of the reversed oxidative TCA cycle occur as carbon is assimilated.

This revealed that H. maritima preferentially uses CO2 as its carbon source, but only when CO2 is in abundant supply. To enable the TCA cycle to run backwards in response to high levels of CO2, the cells harbour huge amounts of the enzyme citrate synthase. A high level of citrate synthase makes it easier to generate acetyl coenzyme A (acetyl-CoA) molecules, which exit the reversed oxidative TCA cycle by forming pyruvate, which is converted to lipids, sugars and amino acids (Fig. 1). This in turn, invites CO2 to enter the cycle. In this way, high environmental CO2 levels push the cycle in the direction of converting CO2 to acetyl‑CoA.

This would cause a logjam at the acetyl‑CoA stage of the cycle were it not for the high levels of CO2. The main connection between the reversed oxidative TCA cycle and other metabolic pathways is the molecule pyruvate, which is made by a reaction involving CO2 and acetyl‑CoA. That reaction, like the two other reactions that incorporate CO2 in this cycle, is reversible and can run in either direction. A high CO2 concentration — typically expressed as high partial pressure relative to the total pressure of all the gases present — pushes all three of these reactions forwards. The whole pathway is thereby pushed in the direction of pyruvate production, as long as there is no bottleneck at the reaction catalysed by citrate synthase. High amounts of that enzyme avert this potential bottleneck, and keep cells poised to exploit high levels of CO2 if the environment provides them.

Ecosystems with high CO2 harbour many environments in which resident microbes have genes that encode enzymes of the reversed oxidative TCA cycle, as metagenomics analysis (genome sequencing of microbial communities) has indicated4. However, the presence of genes alone cannot reveal in which direction cells are using a pathway because the environment can dictate the flow of substrates, as this exquisitely detailed example of H. maritima underscores.

Hippea maritima is not the only known example of a bacterium with reversible metabolism. Another example is the bacterium Thermacetogenium phaeum, which grows under conditions similar to those that support H. maritima (high CO2 and an absence of oxygen), but in industrial cellulose-processing reactors5. If the environment offers abundant H2 and CO2, T. phaeum grows using these to make the molecule acetate. However, if those gases become scarce and acetate is abundant, the microbe’s main metabolic reaction runs backwards5, and it survives on the conversion of acetate to H2 and CO2. How it achieves this is unknown. Looking at the genes that microbes use in a given environment can reveal important clues to the secrets of life in microbial communities6. But to really understand the chemical reactions that support microbial life, there is no substitute for studies such as those by Steffens and colleagues, which show us, carbon atom by carbon atom, what cells are doing with the substrates that their environment presents.

Individual microbes, such as H. maritima, and even whole ecosystems, can thrive from the energy supplied by the reaction of H2 with CO2. This not only offers examples of fascinating microbial ecology, but also provides a window into the ancient past, by presenting strategies for growth in conditions thought to be similar to those that the first microbes on Earth encountered3. Those pioneering microbes had to be able to survive on a diet of CO2 because it was the carbon source that the early Earth had available7.

Yet CO2 is only half of the story. To convert CO2 into organic compounds, microbes need a source of energy and electrons. For the first ecosystems on Earth, and for H. maritima today, the source of chemical energy and electrons for CO2 fixation is H2. For four billion years, microbes have been living from the energy provided by the vast amounts of H2 that Earth’s crust constantly generates8. Given the effort that H. maritima invests in making pyruvate from H2 and CO2, it seems almost unimaginable that the very first biochemical pathways could have got going before there were enzymes to assist the carbon-fixing reactions. Yet, surprisingly, H2 and CO2 can form pyruvate overnight without any enzyme involvement if simple metal catalysts, of the kinds found in the oceanic crust, are provided9. This suggests that early metabolism on Earth was built around the naturally occurring chemistry between CO2 and H2 in mineral-rich environments10.

The chemical reactions that underpin the lifestyle of H. maritima thus hark back to a time when the first cells lived in a world of carbon dioxide. By investigating cells that still inhabit such realms today, we can discover some clues about the life and times of the most ancient microbial ancestors.

Nature 592, 688-689 (2021)

doi: https://doi.org/10.1038/d41586-021-00977-1


  1. 1.

    Steffens, L. et al. Nature 592, 784–788 (2021).

    Article  Google Scholar 

  2. 2.

    Krebs, H. A. & Martin, A. Hans Krebs, Reminiscences and Reflections (Clarendon, 1981).

    Google Scholar 

  3. 3.

    Fuchs, G. Annu. Rev. Microbiol. 65, 631–658 (2011).

    PubMed  Article  Google Scholar 

  4. 4.

    Sharon, I. & Banfield, J. F. Science 342, 1057–1058 (2013).

    PubMed  Article  Google Scholar 

  5. 5.

    Keller, A., Schink, B. & Müller, N. Front. Microbiol. 10, 2785 (2019).

    PubMed  Article  Google Scholar 

  6. 6.

    Orsi, W. D. Nature Rev. Microbiol. 16, 671–683 (2018).

    PubMed  Article  Google Scholar 

  7. 7.

    Sossi, P. A. et al. Sci. Adv. 6, eabd1387 (2020).

    PubMed  Article  Google Scholar 

  8. 8.

    Sleep, N. H., Bird, D. K. & Pope, E. C. Phil. Trans. R. Soc. B 366, 2857–2869 (2011).

    PubMed  Article  Google Scholar 

  9. 9.

    Preiner, M. et al. Nature Ecol. Evol. 4, 534–542 (2020).

    PubMed  Article  Google Scholar 

  10. 10.

    Baross, J. A. Nature 564, 42–43 (2018).

    PubMed  Article  Google Scholar 

Download references


Nature Briefing

An essential round-up of science news, opinion and analysis, delivered to your inbox every weekday.

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing