With formic acid towards CO2 neutrality


May 15, 2023

(Nanowerk News) New synthetic metabolic pathways for carbon dioxide fixation can not only help reduce the carbon dioxide content in the atmosphere, but also replace conventional chemical manufacturing processes for pharmaceuticals and active ingredients with carbon neutral biological processes. new study (Nature Communications, “Engineering a novel to nature cascade for phosphate-dependent formate to formaldehyde conversion in vitro and in vivo”) demonstrated a process that can convert carbon dioxide into a valuable material for the biochemical industry via formic acid.

Given the increasing emission of greenhouse gases, carbon capture, sequestration of carbon dioxide from large emission sources, is an urgent problem. In nature, carbon dioxide assimilation has occurred for millions of years, but its capacity is far from sufficient to compensate for human-made emissions. yellow discoloration in laboratory samples Format can be envisioned as the core of a carbon-neutral bioeconomy, in that it is generated from CO22 by (electro)chemical means and converted into value-added products through engineered enzymatic or microbial cascades. The key step in expanding the assimilation of synthetic formate is its thermodynamically challenging reduction to formaldehyde, seen here as a yellow discoloration. (Image: Max Planck Institute for Terrestrial Microbiology, Geisel)

Researchers led by Tobias Erb at the Max Planck Institute for Terrestrial Microbiology used nature’s toolbox to develop a new way of fixing carbon dioxide. They have now successfully developed an artificial metabolic pathway that produces highly reactive formaldehyde from formic acid, a possible intermediate product of artificial photosynthesis. Formaldehyde can be incorporated directly into several metabolic pathways to form other valuable substances without toxic effects. As in any natural process, two main components are required: Energy and carbon. The former can be provided not only by direct sunlight but also electricity – for example from solar modules.

Formic acid is the C1 building block

In the added value chain, carbon sources vary. carbon dioxide is not the only option here, all monocarbons (building blocks of C1) are questionable: carbon monoxide, formic acid, formaldehyde, methanol and methane. However, almost all of these substances are highly toxic – either to living organisms (carbon monoxide, formaldehyde, methanol) or to the planet (methane as a greenhouse gas). Only formic acid, when neutralized to its basic formate, is tolerated by many microorganisms at high concentrations.

“Formic acid is a very promising carbon source,” emphasized Maren Nattermann, first author of the study. “But turning it into formaldehyde in a test tube is quite energy intensive.” This is because the salts of formic acid, formate, cannot be converted easily into formaldehyde. “There’s a serious chemical barrier between the two molecules that we have to link up with biochemical energy – ATP – before we can carry out the actual reaction.”

The goal of researchers is to find a more economical way. After all, the less energy needed to get carbon into metabolism, the more energy is left to drive growth or production. But such a path does not exist in nature.

“It takes creativity to find so-called promiscuous enzymes with multiple functions,” says Tobias Erb. “However, the discovery of the enzyme candidate is only the beginning. We are talking about reactions that you can count because they are very slow – in some cases, less than one reaction per second per enzyme. Natural reactions can occur a thousand times faster.” This is where synthetic biochemistry comes in, says Maren Nattermann: “If you know the structure and mechanism of enzymes, you know where to step in. Here, we benefited significantly from the early work of our colleagues in basic research.”

High throughput technology accelerates enzyme optimization

Enzyme optimization consists of several approaches: building blocks are specifically exchanged, and random mutations are generated and selected for ability. “Format and formaldehyde are both very suitable because they can penetrate cell walls. We can introduce formate into the cell culture medium that produces our enzymes, and after a few hours convert the resulting formaldehyde into a non-toxic yellow dye,” explains Maren Nattermann.

The results would not be possible in such a short amount of time without using high throughput methods. To achieve this, the researchers are working closely with their industrial partner, Festo, based in Esslingen, Germany. “After about 4000 variants, we achieved a fourfold increase in production,” says Maren Nattermann. “We have thus created the basis for the Escherichia coli microbe model, a biotechnological workhorse of microbes, for growing on formic acid. However, for now, our cells can only produce formaldehyde, not convert it further.”

With collaborating partner Sebastian Wenk at the Max Planck Institute of Molecular Plant Physiology, the researchers are currently developing strains that can take the intermediate and incorporate it into central metabolism. In parallel, the team is conducting research with a working group at the Max Planck Institute for Chemical Energy Conversion led by Walter Leitner on the electrochemical conversion of carbon dioxide to formic acid. The long term goal is an “all-in-one platform” – from carbon dioxide through electrobiochemical processes to products such as insulin or biodiesel.


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