"We can produce anything"

“I have food companies asking me: What can you make? My answer is: What do you want me to make? We can make anything.”

These are the words of Associate Professor José L. Martinez, who conducts research and teaches precision fermentation at DTU, and he sums up the past decade's fast-paced development of a technology that can help the world to a more sustainable production of just about anything.

Egg whites, cheese, yogurt, milk, vitamins, fragrances, colouring agents, flavour additives, vaccines, and cancer and malaria medicine are just some of the things that are manufactured today using components produced with precision fermentation.

Fermentation is a word that most people probably associate with the process of producing beer, bread, sauerkraut or its ‘hip’ counterpart of the East, kimchi. Fermentation utilizes microorganisms such as bacteria and yeasts that already exist in nature. And this is exactly where fermentation differs from precision fermentation. Because the microorganisms involved in precision fermentation are designed for the specific purpose, says José L. Martinez:

“In precision fermentation, microorganisms such as bacteria, fungi, microalgae, or yeast cells are utilized to produce the substances we need. But in order to get the organisms to produce the substances, they must first undergo a couple years’ development work in a laboratory where they are specially designed using genetic engineering.”

CRISPR changed everything

One of the most important tools for this redesign is CRISPR. Simply put, CRISPR can be used to ‘cut’ out genes of a plant or another living organism and insert them into a new cell. The inserted gene contains the code for the substance to be manufactured. If the process is successful, the genetically modified cell can now produce the substance.

Precision fermentation has been known for decades, and Novo Nordisk has long utilized it to produce insulin. But the field has skyrocketed over the past decade due to the CRISPR technology, which became available in 2012.

“Before CRISPR, genetic modification of a microorganism was a difficult, slow, and boring process, and only possible with a few organisms. With CRISPR, it suddenly became easier, and we can now insert genes into a wider variety of microorganisms,” says José L. Martinez, who had to give up modifying a type of yeast cell himself before the birth of the CRISPR technology, despite four years of strenuous efforts. With CRISPR, Martinez and his colleague at DTU Bioengineering, Professor Uffe Hasbro Mortensen, succeeded in modifying the cell in two years.

Before CRISPR, genetic modification of a microorganism was a difficult, slow, and boring process, and only possible with a few organisms. - ASSOCIATE PROFESSOR JOSÉ L. MARTINEZ, DTU BIOENGINEERING

Achilles heel of the technology

Although it is technologically possible to have microorganisms produce anything in a laboratory, the Achilles heel of precision fermentation is scaling up the process. Upscaling is about increasing the production of a given substance from a few milligrams in the laboratory to a yield of several tons in a factory. This means extra work for the researchers.

“We can make anything in the laboratory, but as soon as we scale up the production up, we encounter difficulties. When the microorganisms go from living in a 1-liter fermentation tank to a larger tank, they often respond to changes of, e.g., temperature, osmotic pressure, and oxygen and salt content, etc., and the production of the given substance may slow down or even stop. Thus, we also work a lot on manipulating the microorganisms, so they can cope with the changes. At worst, we will have to start over and find a new microorganism,” says José L. Martinez, who explains that it is becoming continuously easier to search for nature's own answer to microorganisms that are robust enough to cope with upscaling.

“Thanks to the rapid technological development in areas such as genome sequencing, robots, big data handling, and artificial intelligence, we can now screen thousands of microorganisms in a week, as opposed to around one hundred just ten years ago,” says José L. Martinez, adding:

“The portfolio of potential microorganisms to utilize has grown enormously because we can find them now. Nature has actually already invented all solutions. We just need to find them.”

At Pilot Plant at DTU Chemical Engineering at Lyngby Campus biotechnological solutions is being upscaled. Photo: Jørgen True 

Big market growth on the horizon

In order for precision fermentation to replace dairy cows, beef cattle, chickens, oil, gas, or coal, it is crucial to find solutions that enable the microorganisms to produce large amounts of the desired substances. Otherwise, the processes will not be profitable for the companies as the end products end up being far too expensive.

Despite the challenges of upscaling, precision fermentation is predicted to reach new heights in the coming years. According to the Wall Street-based research firm Polaris Market Research, the global precision fermentation market was worth $1.3 billion in 2021 and will grow by 48 per cent annually until 2030. The market analysis predicts that alternatives that can lead to substitutes for meat, fish, and eggs will drive growth on the precision fermentation market.

A growth, which the research firm attributes to the increasing demand for food, that does not burden the environment or the climate but instead is facilitated with a lower energy consumption, lower CO₂ emissions, a lower water consumption, and without the use of huge areas of agricultural land. Last, but not least, production will be able to move geographically closer to consumers, thus also avoiding the energy consumption and CO₂ emissions associated with transporting products over great distances.

Important player in the green transition

These perspectives have led to precision fermentation being touted as one of the most important technologies in the green transition. But an even greater potential lies ahead, says José L. Martinez:

“In the coming years, there will be a change in the way we feed our microorganisms. They have to feed on something inside their steel tanks, and today we feed them sugar, among other things. But we are developing new feed solutions because we find microorganisms that can live off waste and by-products from businesses, greenhouse gases or even plastic. Enzymes have been found that can biodegrade plastic into compounds that we can use as feed for the microorganisms. This is truly mind-blowing. Just imagine that one day we will be able to produce medicine or food using our plastic waste. It's revolutionary. It’s the essence of green transition.”