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Nature-inspired synthetic metabolic pathway converts carbon dioxide into valuable biochemicals

A groundbreaking study published in Nature Communications presents an innovative approach to address the pressing issue of rising greenhouse gas emissions. The research, led by Tobias Erb and his team at the Max Planck Institute for Terrestrial , focuses on developing new synthetic for carbon dioxide fixation.

These pathways not only have the potential to reduce atmospheric carbon dioxide levels but also offer a promising alternative to conventional processes in the pharmaceutical and biochemical industries. By harnessing nature's own mechanisms, the researchers have devised a method to convert carbon dioxide into formic acid, a valuable material for the biochemical industry.

Formic acid, produced through an artificial metabolic pathway, can be further transformed into highly reactive formaldehyde. This formaldehyde can then serve as a building block for the of various valuable substances, without any toxic effects. Similar to natural processes, this transformation requires two key components: energy and carbon. Energy can be supplied through direct sunlight or electricity, such as that generated by solar modules.

The significance of this research lies in its potential to combat carbon dioxide emissions through carbon capture and utilize this greenhouse gas as a valuable resource. By developing synthetic metabolic pathways, scientists aim to expand nature's capacity for carbon dioxide assimilation and create sustainable, carbon-neutral processes for the production of essential compounds.

The findings of this study mark an important step forward in the pursuit of carbon capture technologies and the development of environmentally friendly alternatives to traditional manufacturing methods. With further advancements and refinement, these synthetic pathways could contribute significantly to mitigating climate change while promoting sustainable industrial practices.

Formic acid is a C1 building block

In the realm of carbon source options within the value chain, carbon dioxide is not the sole contender. Other monocarbons, such as carbon monoxide, formic acid, formaldehyde, methanol, and methane, come into consideration. Nevertheless, most of these substances possess high toxicity—either to living organisms (carbon monoxide, formaldehyde, methanol) or to the (methane as a potent greenhouse gas). However, formic acid stands out as a favorable carbon source, especially when neutralized to formate, as it is well-tolerated by many even at high concentrations.

Maren Nattermann, the study's first author, emphasizes the potential of formic acid as a carbon source but acknowledges that converting it to formaldehyde in the laboratory setting is energy-intensive. The conversion from formate, the salt of formic acid, to formaldehyde encounters a significant chemical barrier that necessitates the expenditure of biochemical energy in the form of ATP before the actual reaction can occur.

The researchers aimed to discover a more efficient approach, recognizing that minimizing the energy required to incorporate carbon into metabolism would leave more energy available for growth or production. However, such a pathway does not exist naturally. Tobias Erb remarks that identifying “promiscuous enzymes” with multiple functions requires creativity. Nonetheless, the identification of candidate enzymes is only the initial step, as these reactions occur at a sluggish pace—sometimes less than one reaction per second per enzyme. In contrast, natural reactions can transpire thousands of times faster.

This is where synthetic plays a pivotal role, according to Maren Nattermann. Understanding an enzyme's structure and mechanism enables targeted interventions. In this endeavor, the researchers benefit significantly from the groundwork laid by their counterparts in basic research.

High-throughput technology speeds up enzyme optimization

The optimization of enzymes involved a combination of strategies, including targeted exchanges of specific building blocks and the generation and selection of random mutations based on their functional capabilities. Maren Nattermann explains that both formate and formaldehyde were particularly well-suited for this purpose as they can easily penetrate cell walls. By introducing formate into the culture medium of enzyme-producing , the researchers were able to convert the resulting formaldehyde into a non-toxic yellow dye within a few hours.

The rapid progress achieved in this study was facilitated by the use of high-throughput methods, made possible through collaboration with the industrial partner Festo, based in Esslingen, Germany. Maren Nattermann highlights that after screening around 4,000 enzyme variants, they achieved a fourfold improvement in production. This accomplishment has laid the foundation for the model microbe Escherichia coli, widely used in , to thrive on formic acid. However, at present, the cells can only produce formaldehyde and cannot further convert it.

In collaboration with Sebastian Wenk at the Max Planck Institute of Molecular Plant , the researchers are currently working on developing a strain capable of assimilating the intermediates and integrating them into the central metabolism. Simultaneously, the team is conducting research in partnership with a group led by Walter Leitner at the Max Planck Institute for Chemical Energy Conversion on the electrochemical conversion of carbon dioxide to formic acid. The ultimate objective is to create an “all-in-one platform” that encompasses the entire process, starting from carbon dioxide and utilizing an electrobiochemical approach to generate valuable products like insulin or biodiesel.

Source: Max Planck Society

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