New synthetic metabolic pathways for carbon dioxide fixation can not only help reduce the carbon dioxide content in the atmosphere, but also replace traditional chemical manufacturing processes for drugs and active ingredients with carbon-neutral biological processes. A new study demonstrates a process that can turn carbon dioxide into a valuable material for the biochemistry industry via formic acid.
In light of rising greenhouse gas emissions, carbon capture, and sequestration of carbon dioxide from sources of large emitters, is an urgent issue. In nature, carbon dioxide has been absorbed for millions of years, but its capacity is far from sufficient to compensate for man-made emissions.
Researchers led by Tobias Erb of the Max Planck Institute for Terrestrial Microbiology are using Nature’s Toolkit to develop new methods for carbon dioxide fixation. They have now succeeded in developing a synthetic metabolic pathway that produces highly reactive formaldehyde from formic acid, a potential intermediate product of artificial photosynthesis. Formaldehyde can be fed directly into many metabolic pathways to form other valuable substances without any toxic effects. As in the natural process, two basic elements are needed: energy and carbon. The former can be provided not only by direct sunlight but also by electricity – for example from solar modules.
Formic acid is the building block of C1
Within the added value chain, the source of carbon is variable. Carbon dioxide is not the only option here, all single carbon compounds (the building blocks of C1) are in question: 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 in high concentrations.
“Formic acid is a very promising carbon source,” confirms Maren Nattermann, first author of the study. “But it takes a lot of energy to convert it into formaldehyde in a test tube.” This is because the formic acid salt cannot be easily converted into formaldehyde. “There is a serious chemical barrier between the two molecules that we must bond to the biochemical energy – ATP – before we can carry out the actual reaction.”
The researcher’s goal was to find a more economical method. After all, the less energy it takes to feed carbon into metabolism, the more energy is left to drive growth or production. But such a path does not exist in nature. “It takes some creativity to discover the so-called mixed enzymes with multiple functions,” says Tobias Erb. “However, the discovery of candidate enzymes is only the beginning. We are talking about reactions that you can count on because they are so slow – in some cases, as little as one reaction per second per enzyme. Natural reactions can happen a thousand times faster.” This is where synthetic biochemistry comes in, says Maren Nattermann: “If you know the structure and mechanism of an enzyme, you know where to get involved. Here, we benefit greatly from the preliminary work of our colleagues in basic research.”
High yield technology accelerates enzyme optimization
Enzyme optimization consisted of several methods: building blocks were specifically exchanged, and random mutants were generated and selected for ability. “Both formaldehyde and formaldehyde are a great fit because they penetrate cell walls. We can put formate into culture medium for cells that produce enzymes, and after a few hours convert the formaldehyde produced into a non-toxic yellow dye,” explains Marien Nattermann. .
The result would not have been possible in such a short time without the use of highly productive methods. To achieve this, the researchers collaborated with their industrial partner Festo, based in Esslingen, Germany. “After about 4,000 variants, we’ve achieved a fourfold improvement in production,” says Maren Nattermann. “In doing so, we have established the basis for a microbe model Escherichia coli, the microbial backbone of biotechnology, to grow on formic acid. But right now, our cells can only produce formaldehyde, not convert it into more.”
With collaboration partner Sebastian Wenck at the Max Planck Institute for Molecular Physiology of Plants, the researchers are currently working on developing a strain that can take up intermediates and bring them into the central metabolism process. In parallel, the team is conducting research with a working group at the Max Planck Institute for Chemical Energy Conversion headed 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 via a biochemical process to products such as insulin or biodiesel.