CHICAGO — While precision fermentation technology has been around for more than 30 years, it’s only now being recognized for its potential to produce food and food ingredients in a sustainable way.

It’s already used in the production of several food ingredients, including natural flavors, rennet, vitamins and stevia. But it is recent advancements in cellular agriculture — the process of using precision fermentation to produce genuine animal proteins — that is fueling interest and innovation.

“There is a direct line between food production, climate, socioeconomic opportunities and equity,” said Nicki Briggs, vice president of corporate communications for Perfect Day, Berkeley, Calif., and chair of the Precision Fermentation Alliance (PFA). “How we make our food is one of the foundational ways to change the world around us.”

Founded one year ago, the PFA serves as an industry voice and global convener for this emerging industry.

“Precision fermentation is the newest chapter in the history of making food without animals,” said Maija Itkonen, cofounder and chief executive officer of Onego Bio, a US-Finnish food ingredient company. “It allows us to provide people with food that is sustainable, tasty and healthy, without cutting any corners or making any compromises.”

Fermentation without the “precision” has been around forever. That’s how grapes turn into wine, bread rises and kombucha becomes effervescent and probiotic. Precision fermentation is, as the name suggests, more precise — it’s a calculated technology.

With precision fermentation, bioengineering techniques are used to program microorganisms by giving them a specific genetic code to produce a compound of interest when fermented under precise conditions. The genetic code is the exact copy of the DNA sequence found in a digitized database on animal or plant DNA sequence; however, it requires no animal or plant involvement. The result is a molecularly identical ingredient produced by microorganisms.

Sound a little scary? That’s what the PFA hopes to change. One of the biggest hurdles is communicating that while precision fermentation uses genetic engineering techniques, it is different from genetically modified crops. The technology uses genetically engineered microorganisms in the fermentation process, but the modified organisms are filtered out after fermentation, leaving only the specific compounds or ingredients that they have been designed to create. If the end product does not contain any genetically modified material, it is not considered a GMO or required to be labeled as “bioengineered” by current US regulatory standards.

Since 1990, rennet has been produced this way without disclosure to consumers. Rennet is a complex set of enzymes produced in the stomachs of ruminant mammals, which is historically where it was sourced for cheesemaking. The enzymes, mainly chymosin, turn the casein in milk into cheese curds.

With genetic engineering, scientists were able to isolate rennet genes from animals and introduce them into microorganisms, which then produce chymosin from a fermentation broth. The genetically modified microorganisms are killed after fermentation, and the chymosin is isolated.

Such precise fermentation enables the production of large amounts of specific compounds. EverSweet stevia sweetener, for example, is produced using the technology by Avansya, in the joint venture between Cargill, Minneapolis, and dsm-firmenich, Heerlen, The Netherlands. The ingredient contains such components of the stevia leaf as steviol glycosides Reb M and Reb D without the leaf.

“Reb M and Reb D exist in the leaf in such low levels — less than 1% — that it’s simply not economically or commercially viable to produce a sweetener made from these sweet-tasting molecules using a traditional agronomic approach,” said Carla Saunders, senior marketing manager for high-intensity sweeteners, Cargill. “As a result, we moved from the field to fermentation, using a specially crafted yeast to produce the same Reb M and Reb D molecules found in minute quantities in the stevia leaf. Using fermentation, we can produce EverSweet in quantities and at a price-point that makes wide-spread commercial use possible. This in turn opens the door for greater innovation related to sugar reduction across a myriad of food and beverage categories.”

The approach also offers environmental benefits. For EverSweet, the sustainability credentials include a 60% lower ecological footprint, 70% less land use and a 60% lower carbon footprint than bio-converted Reb M, according to Cargill.

Another company choosing precision fermentation over crop production is Phytolon, an Israeli startup using licensed technology from the Weizmann Institute of Science. The technology involves using baker’s yeast to produce natural colors.

Most natural food colors are derived from fruits and vegetables, which require a lot of natural resources and are also dependent on the weather. With precision fermentation, the company uses two strains of baker’s yeast, one modified to secrete a water-soluble yellow pigment and the other to secrete a water-soluble purple pigment. Phytolon then combines the two to produce such colors as vibrant reds and pinks to oranges that are stable across a wide pH range and may be produced consistently all year long.

Phytolon partnered with Ginkgo Bioworks, Boston, in February 2022 to enhance the efficiency of the yeast strains. At the end of January 2024, the companies announced they completed their first milestone of producing the entire yellow-to-purple spectrum.

“This achievement puts our colors at the forefront to efficiently replace artificial dyes in our food and create a healthy and sustainable world,” said Tal Zeltzer, co-founder and chief technology officer of Phytolon. “Our clients are now able to explore high-performing natural colors in their brands, covering the full range from purple to pink, red, orange and yellow shades.”

More than an ingredient

Precision fermentation technology not only may be used to produce ingredients, but it also may be used to replicate whole foods, such as animal-free beef burgers. But as of now, there are many unknowns in the space in terms of regulatory approvals and scalability. But it is this growing conversation about cellular agriculture that has put precision fermentation into the spotlight.

Onego Bio, Espoo, Finland, has developed Bioalbumen animal-free egg proteins. Onego Bio’s ingredient is bio-identical to ovalbumin, the primary protein in egg white. It provides the same functionality and nutrition without the egg from chickens, according to the company.

Perfect Day did this with whey proteins. The company was founded 10 years ago and debuted a precision fermented whey protein in 2020. The animal-free whey proteins may be used in the same applications as the animal-based ingredient — everything from sports nutrition to baked foods — while delivering the same taste, texture and nutrition. They also may be used to produce animal-free dairy products, such as ice cream and yogurt.

Perfect Day’s whey protein reduces blue water consumption by up to 99%, greenhouse gas emissions by up to 97% and non-renewable energy use by up to 60%, when compared to conventional animal production methods, according to the company.

Imagindairy, an Israeli-based food tech startup with offices in San Francisco, now owns and operates industrial-scale precision fermentation production lines focused on the production of all types of animal-free dairy ingredients. The facility allows Imagindairy access to production at more than 100,000 liters of fermentation capacity, with planned capacity expansion to triple this volume within about two years.

“Having just entered the landscape three years ago, this achievement is a big step forward for us,” said Eyal Afergan, co-founder and CEO. “We’ve overcome industry-wide hurdles that have previously been holding precision fermentation dairy back, including the production capacity bottleneck and ensuring that unit economics make sense across the supply chain. This will enable our customers to put animal-free dairy products on shelf at cost parity to traditional dairy, without compromising on quality. It’s a substantial breakthrough and important step that will allow us to support mass-market adoption, transition to an industrial company and speed up the development of other milk proteins.”

Imagindairy received a “no questions” response letter from the US Food and Drug Administration at the end of 2023 for the Generally Recognized as Safe notice submitted by the company. It’s important to note that because animal-free egg and dairy ingredients are genetic duplications of the animal-based formats, the same allergies and sensitivities exist for consumers, and the FDA requires disclosure.