Tomorrow’s climate-friendly chemical plants

Monday 28 Feb 22
by Henrik Olsen


Alex Toftgaard Nielsen
DTU Biosustain
+45 21 79 89 06


Fermentation is a process in which microorganisms—for example yeast cells or bacteria—produce chemical energy through the conversion of sugar or other organic molecules. The microorganisms use the energy in their propagation. In this process, there is sometimes a residual product in the form of, for example, alcohol or an acid.

The fermentation takes place in large tanks, where the microorganisms that produce the desired residual product are cultivated. Many fermentation processes are well known, for example the production of wine and beer. In more advanced industrial production, genetically modified organisms can be used to form substances that they would otherwise not form naturally.

Source: Den Store Danske

Specially designed bacteria are used to combat climate change when Danish biotech company Cysbio develops the chemical plants of tomorrow.

Global climate change has created a great need for technologies that limit carbon emissions into the atmosphere. The focus has primarily been on the battle to develop alternative forms of energy that can reduce the use of coal, oil, and gas. But another battleground is the organic-chemical industry, where petrochemical processes—based on the conversion of fossil oil and gas—have been completely dominant for nearly 100 years.

Now the Danish company Cysbio is facing a breakthrough in which sugar replaces oil as the principal basic substance, and where coli bacteria function as small efficient biological chemical plants when they convert the sugar and form amino acids and other biochemicals.

Spin-out from DTU Biosustain

The biotech company Cysbio saw the light of day in 2019 as a spin-out from DTU Biosustain, which is a research centre founded by the Novo Nordisk Foundation for the purpose of developing sustainable biotechnologies.

Alex Toftgaard Nielsen was employed as a professor at DTU Biosustain when the centre was established in 2011, and he has gathered a group of researchers who have worked determinedly with bacteria and fermentation techniques that are more climate and eco-friendly than conventional methods.

“Cysbio was established after more than seven years of research at DTU Biosustain, where two postdoc researchers in my group—Christian Bille Jendresen and Hemanshu Mundhada—have developed the two main technologies that we use in Cysbio,” explains Alex Toftgaard Nielsen.

"We hope that our first products will be launched on the market at the end of 2022 or beginning of 2023."
Henrik Meyer, CEO, Cysbio

Together with Henrik Meyer—who has extensive managerial experience from the biotech companies Novozymes and Evolva, among other companies—the three researchers make up the management team in Cysbio.

Amino acids

At DTU Biosustain, the researchers focused on a specific type of amino acids used in a number of areas, including in food products, cosmetics, and pharmaceuticals. Conventional production of these products is often energy intensive and based on fossil oil, and it also involves toxic chemicals in some cases. The researchers wanted to change this by using fermentation processes in which microorganisms convert sugar in their propagation process. The choice of microorganism fell on E. coli bacteria.

“E. coli is a real workhorse. And it has been a model organism for many years, so it’s well described. In addition, there are detailed computer models that can calculate what happens to the coli bacterium when you change it, and we have utilized this,” says Alex Toftgaard Nielsen.

The researchers therefore started genetically engineering E. coli so that the bacterium began producing amino acids.

“We’ve designed the bacteria so that they grow slower and slower, the more time that passes, and they end up instead using the most energy and carbon from the sugar than on producing chemicals,” says Alex Toftgaard Nielsen.

Useful mutations

Getting the bacteria to produce the coveted biochemicals was not completely unproblematic. The tests quickly showed that high concentrations of amino acids were toxic to E. coli, resulting in the bacteria dying before they had produced sufficient quantities.

“We’ve spent a lot of energy on making the bacteria tolerant to the product,” explains the professor.

This has been achieved by gradually increasing the concentration of the substance against which the bacteria are to become resistant.

“You actually utilize that the bacteria start mutating. The mutations that make the bacteria most resistant make the cells grow faster, and they will then dominate,” says Alex Toftgaard Nielsen.

By subsequently genome sequencing the bacteria, the researchers were able to analyse the resistant mutations. In some cases, they were used directly in the further development process. In other cases, the researchers used the analysis results to design bacteria that contained the most successful mutations.

The result of the researchers’ work meant that they were now able to produce amino acids that could compete on price with their oil-based counterparts, and which reduce carbon emissions into the atmosphere considerably relative to conventional petrochemical production. The foundation for establishing a commercial business had been laid.

First commercial products are in the pipeline

Henrik Meyer—CEO of Cysbio—says that two amino acids are on their way to commercial production. One of these amino acids will be used for food production. However, Henrik Meyer also sees great commercial opportunities in the feed industry. The other amino acid product will be widely used in pharmaceuticals and cosmetics, but there is also a potential market in food supplements.

“We hope that our first products will be launched on the market at the end of 2022 or beginning of 2023,” says Henrik Meyer.

In the longer term, Cysbio expects to develop other biochemicals, including some types that can be used in paints and pharmaceuticals, as well as in the polymer industry, where they can form part of the production of plastic substitutes and be used in adhesives.


An essential point in any experimental production is upscaling from laboratory test setup to factory. In the case of Cysbio, this is from 1-litre bioreactors to 200,000-litre fermentation tanks necessary to produce the amino acids in quantities that are commercially interesting.

Here, Cysbio has entered into a partnership with the Chinese chemical company Zhejiang NHU, which has invested an amount running into millions in Cysbio. Zhejiang NHU will build the huge fermentation tanks and be responsible for the production of the first two commercial amino acid products.

In the longer term, however, the plan is for Cysbio to build production facilities in Europe, where it will be much simpler to obtain approvals for sales of the products in the EU.

Cysbio is developing zosteric acid for ship paints and pharmaceuticals

Cysbio does not only work with amino acid production. Another product with great commercial potential is zosteric acid, which Cysbio also produces using E. coli bacteria. The substance can potentially be used in paints and in the manufacture of pharmaceuticals.

“Zosteric acid is known to have a strong antibiotic effect that prevents microorganisms from sticking to surfaces, and this applies to bacteria, fungal spores, virus particles, and larger organisms, so we thought it was an exciting substance to work with,” says Alex Toftgaard Nielsen, Professor at DTU Biosustain and Head of Research at Cysbio.

Zosteric acid is known from eelgrass, where it is probably excreted to control the growth of microorganisms on the surface of the leaves and reduce photosynthesis. It is a substance with a large application potential, but it is difficult to extract from eelgrass, and it has so far been complicated to produce in the laboratory.

E. coli does not have a natural ability to produce zosteric acid. Therefore, Christian Bille Jendresen from the Professor’s research group at DTU Biosustain started looking for genes in other organisms that could enable the bacterium to produce the coveted acid. He succeeded in finding an enzyme which—through genetic engineering—could make E. coli form zosteric acid via fermentation. The technology used is called sulphation, as a sulphate group is added to the finished product.

The professor sees great commercial opportunities in the technology. The obvious application is for ship paints and hospital paints, where unwanted growth of microorganisms on surfaces can be prevented. But the technology can also be used in the production of pharmaceuticals, where the sulphated substance can improve solubility and degradability, which are important to how the pharmaceutical is assimilated in the body. In the longer term, the technology may also find application in the production of new types of plastics and adhesives.

The project on further development and upscaling of the sulphation technology was supported with DKK 18 million in 2020 via the EU programme Horizon 2020, FTI (Fast Track to Innovation).

News and filters

Get updated on news that match your filter.