Crafting Proteins with Precision Fermentation

I had a chance to briefly chat with the founder of Every at the AI * Vegan meetup (I know, everything has to be AI in SF now). They make cruelty-free products like egg proteins. As I was asking him how exactly they produce it, he mentioned that they use precision fermentation. I’ve never heard of the term, but as I asked him more questions, I figured that they are probably just using the same technology Genentech used for their insulin production. With some googling afterwards, I was convinced that it is a combination of recombinant DNA (rDNA) technology and fermentation.

It is probably not too much to say that modern biotechnology originated in 1973 with the invention of recombinant DNA, which led to medical drug development of insulin and success of biotech company behind it, Genentech.

In the early 1970s, two scientists, Herbert Boyer and Stanley Cohen, crossed paths at a scientific conference. Boyer, a biochemist at the University of California, was researching enzymes that could cut DNA precisely, while Cohen, a geneticist from Stanford, was focused on finding ways to transfer DNA between organisms. When Cohen heard Boyer speak about his research on DNA-cutting enzymes, he had a realization: these enzymes could help him solve a key problem in his own work.

After the presentation, Cohen approached Boyer with an idea: what if they combined their research to cut DNA from one organism and insert it into another, creating new, recombined DNA? This idea led to the invention of recombinant DNA technology, a method that allows scientists to combine DNA from different organisms and give them new properties. Together, the two began a collaboration that would lead to experiments showing that they could insert DNA into bacteria, which would then reproduce the foreign DNA and express it.

Their early experiments showed promise, but the real breakthrough came when they realized that this technique could be used to produce proteins like insulin. At the time, insulin, a hormone essential for managing diabetes, was extracted from animals—a slow and costly process. But with recombinant DNA technology, the human gene responsible for insulin production could be inserted into bacteria. These bacteria, in turn, could be grown in large quantities to produce insulin, making it easier to manufacture and more accessible to those who needed it.

This simple idea—using bacteria as tiny factories to produce human insulin—was revolutionary for diabetes treatment and became one of the first major commercial applications of recombinant DNA. It also laid the foundation for the biotechnology industry, allowing scientists to create medicines and therapies in ways that were previously impossible. Genentech, founded by one of the scientists Herbert Boyer and ex-venture capitalist Robert A. Swanson, commercialized insulin, and it went public in 1980, making it one of the first biotech firms to do so.

Now, alt protein companies like Every use the same technology to produce animal proteins by taking advantage of the natural fermentation process.

Fermentation has been used by humans for thousands of years to produce food and drink, and it is still used in many of the same ways today. It is a natural metabolic process where microorganisms, like yeasts or bacteria, convert sugar into other products like alcohol, acids, or gases. Beer, cheese, sake, yogurt, kimchi, and bread are all produced through fermentation.

However, in nature, fermentation cannot produce anything it wants. This is where recombinant DNA comes in. You can give microorganisms like yeasts genetic instructions so that they can produce what we desire like egg proteins through their fermentation.

I’d imagine that the simplified steps of eggs protein precision fermentation look like this:

  1. Gene Extraction: Scientists first extract the desired gene from the source DNA using DNA-cutting enzymes called Restriction enzymes. For example, they can take the gene responsible for egg proteins production from chicken’s DNA.
  2. Inserting the Gene: The gene is inserted into plasmids of a host organism, such as bacteria or yeasts cells. The plasmids are like tiny bonus instruction booklets inside the cell. Then these host organisms will act as tiny factories for producing the desired egg proteins.
  3. Growing the Cells: The genetically modified organisms, which carries the recombinant DNA, are grown in a controlled environment like large cultures or bioreactors. They are fed sugar or other nutrients. As they multiply, they express the egg proteins encoded by the inserted recombinant DNA.
  4. Harvesting: The target product (e.g., egg proteins) is collected from the cell culture and purified using techniques like centrifugation, filtration, chromatography, or precipitation before production.

Precision fermentation should be much more scalable today compared to capex-heavy solutions like cultivated meat. It may be a good mid-term solution or a viable option for some forms of animal proteins.


Date
November 20, 2024