By Jeanne Yacoubou

In 2021, The VRG reported on “animal-free” whey (ProFerm) manufactured by Perfect Day using precision fermentation (PF) involving the genetic material taken from the blood of Dominette, an 8-year-old Montana cow. Since then, PF-derived whey, specifically a protein found in whey called beta-lactoglobulin, as well as other bioengineered animal proteins, has been added to a wide variety of foods and beverages, many of which are labeled vegan or “animal-free.” In many cases, these novel, synthetic proteins are labeled “nature identical” or “one-to-one replacements” for animal proteins by their manufacturers.

The rationale provided for the production of these novel proteins by companies manufacturing them often includes the need to feed a burgeoning human population or to meet consumer ethical demands related to animal welfare, carbon emissions, or deforestation. There are varying opinions on these issues.

The first lawsuit challenging “animal-free” branding as a case of deceptive advertising was filed in the United States by GMO/Toxin Free USA and the Organic Consumers Association in 2025, based on an independent analysis of ProFerm by the The groups’ allegations include:

• ProFerm is not structurally identical to “pure” bovine whey and contains very little of it.
• In ProFerm, there is a high percentage of fungal proteins not found in bovine whey.
• As residual leftovers from PF, these fungal proteins constitute a “new” human food source with unknown consequences for human health or nutrition.
• The nutritional profile of “animal-free milk” containing ProFerm differs significantly from that of cow’s milk.

In response to the filing, lawyers for Perfect Day filed a motion to dismiss the lawsuit as reported by the AgFunderNewsletter in June 2025. The complaint argues that the GRAS notification prepared by Perfect Day for the US Food & Drug Administration fully validates the safety of ProFerm. At the time of writing, there is no further information on the status of this lawsuit.

Novel proteins associated with PF products

In its motion to dismiss, Perfect Day referenced the lack of evidence of human toxicity or allergenicity of the novel fungal proteins produced by PF using the filamentous fungus Trichoderma reesei, the microbe genetically engineered by the company to manufacture ProFerm. Although this may be true, the possible effect(s) of novel fungal proteins on the human gut microbiome or its role in human health and nutrition have not been thoroughly examined. Since some recent research shows that the bioactive nature of food molecules, protein functionality, and the human gut microbiome are affected by the dynamics of milk protein-sugar complexes, novel fungal protein-sugar complexes in lab-made animal proteins such as whey could have the same effect.

A research team considered this topic in a 2025 peer-reviewed paper by investigating whey proteomics and the associated glycobiology of whey. As described in this short video, proteomics is the study of the structure, function, and interactions of all the proteins (the proteome) in an organism or cell type at a specific time and under certain conditions. Glycobiology refers to the study of the structure and function of sugar molecules.

In living organisms including humans, proteins do not act in isolation. They are often chemically associated with a wide variety of sugar molecules such as N-glycans. For optimal health, these molecular structures and attachments must correspond exactly to how they exist in nature (that is, before genetic engineering).

In this study, the investigators wanted to determine if “yeast-synthesized” whey was identical to bovine whey protein isolate. They also examined the effects of N-glycans that are chemically attached to whey on human gut microbial diversity.

The researchers noted the microbe was a yeast, unlike Perfect Day’s Trichoderma reesei. The VRG reached out to the researchers to identify the company that manufactured the bioengineered whey under study or the microbe(s) involved in the genetic transfer, but they declined to tell us. Their paper states only “Yeast-synthesized whey protein was purified from a commercially available food advertised to contain solely yeast-synthesized whey protein and was purchased at a local market.”

The investigators found that while both the yeast-synthesized and the bovine whey were composed mainly of beta-lactoglobulin, only the cow-derived whey contained significant amounts of other proteins, such as alpha-lactalbumin, albumin, and casein S1. In vitro lab experiments using a fecal fermentation model showed bovine whey supported more diverse gut bacteria compared to the yeast-synthesized whey. This result  showed that these two allegedly “identical” whey molecules are not the same in terms of their effect on the gut microbiome.

Similarly, when analyzing glycans attached to the two types of whey molecules, researchers observed that yeast-synthesized whey had fewer glycans attached to it (22 types) and those glycans were structurally different compared to the “structurally and compositionally complex” glycans (78 types) associated with bovine whey. Though subtle, these differences could affect the gut microbiome, human metabolism, or human health. While further research is needed to characterize these possible effects, this analysis shows that yeast-synthesized and bovine whey are not identical. “Functionally, [bioengineered whey] behaves like whey and taste like whey,” said Steven Frese, an author of the research study, commenting in an article publicizing this work. “But at the molecular level, they are decorated differently, and those decorations, called post-translational modifications, appear to influence how our gut microbes respond.”

In their paper, the researchers concluded: “These findings raise important questions as to whether these differences in synthetic proteins lead to significant changes to the gut microbiome in vivo, and whether this may impact the utility of these novel ingredients.”

Echoing this sentiment, Frese added: “This research wasn’t about saying one protein is better than the other. It was about understanding whether they are truly interchangeable. If we are going to introduce novel proteins into the food supply, we need to understand how they behave once they are in the body.”

The contents of this posting, our website and our other publications, including Vegan Journal, are not intended to provide personal medical advice. Medical advice should be obtained from a qualified health professional. We often depend on product and ingredient information from company statements. It is impossible to be 100% sure about a statement, info can change, people have different views, and mistakes can be made. Please use your best judgment about whether a product is suitable for you. To be sure, do further research or confirmation on your own.