Animal-Free Dairy 2025: Are We There Yet?

Impact: 2.7% of GWP

Technology Maturity: Pilot/Scaled-Subsidized

This is Article #13 of a series on the climate technologies shown in my ClimateTech Market Map, with a deeper dive into technical maturity and potential to reduce global warming. Here I'll talk about the status of precision fermented dairy (PFD) as a replacement for animal dairy products. TL;DR - No we're not there yet, but there's a pathway to get there.

Why Precision Fermentation Dairy?

The dairy industry is a mid-tier contributor to climate change due to its methane (cow burps + manure) and nitrous oxide emissions (fertilizer use). Multiple approaches to reduce its GWP impact have been explored including the development of anti-methane cattle vaccines, anti-methane feed additives, and plant-based "taste-alike" replacements.

Another approach to reducing dairy emissions is to replace cows milk with a combination of chemically identical proteins, fats and sugars produced by genetically engineered microbes grown in fermentation tanks. This process is called "cellular agriculture" or "precision fermentation" (PF). When powered with renewable energy, PF Dairy (PFD) can produce milk components at less than 10% of the emissions footprint of animal dairy (8).

During the peak of the engineered food bubble in 2019-2020, with more than $4B of venture capital in the sector, some analysts forecast a rapid cost reduction for PFD to the point where it could cannibalize traditional animal dairy production. One analyst even forecast the global collapse of animal dairy by 2030.

The Trough

But this is not on track to happen. Although some high value dairy protein isolates - like lactoferrin - appear to have profitable economics, I guesstimate that bulk whey and casein products made with PFD appear to be ~3-5x more expensive than animal sourced products as of late 2024.

Large processed food companies also seem to have pulled back from PFD. In February 2023, General Mills discontinued its Bold Cultr test brand developed in partnership with Remilk, a PFD startup, and I can't find follow-up from test marketing of a number of PFD consumer products by Nestle, Mars and Unilever in 2022 and 2023.

The Next Generation

But while this first generation of PFD has disappointed, it would be premature to write it off as a future commodity technology. Many other PF processes deliver low cost product at large scale. PF processes for enzymes and lysine, for example, have accumulated a long track record at industrial scale and now deliver product at a price of $1-3 per kg. This is handily below the $6-7 per kg price of whole protein isolated from animal milk using current processes and also cheaper than the ~$9-16 per kg price of casein proteins from animal milk (3).

This first generation of PFD startups mostly used contract manufacturers with legacy production equipment and plants designed for low volume/high value batch production of pharmaceutical and enzyme products. Future continuous production processes operating at higher scales with more productive microbes should deliver product at a cost that displaces processed animal milk in end-markets like casein and whey protein isolates and perhaps even commodity cheeses. This will take expertise in industrial process engineering, higher microbial productivity and a lot of capital, but it seems reasonably within reach in a 10-15 year timeframe.

Dairy Fundamentals

Dairy is responsible for ~20% of emissions from agriculture worldwide (excluding the emissions allocated to the meat produced by dairy cows), or roughly 2.5 to 3% of Global Warming Potential (GWP). While dairy also contain fats and sugars, dairy's proteins are its most important contribution to human nutrition, constituting about 12% of human protein consumption worldwide.

In addition to emissions, dairy cows also compete with crops for land use, although this varies by region. Globally about 23% of dairy cows feed intake is from cropped animal feeds such as maize and soy. But 77% of intake is from straw/crop residues or pastured grass from land that cannot economically support food crops.

Modern dairy cow breeds in optimized production systems produce milk very cheaply: typically at ~$0.40 per liter, although the very best systems can produce milk at ~$0.05 per liter.

Dairy Products & End-Markets

One of the surprising facts about the dairy market to most consumers is the small share of raw milk production that ends up in a typical supermarket milk carton. The figure below shows the destination for Swiss raw milk production by end market and product segment. Less than 10% of Swiss raw milk ends up in a supermarket milk carton vs 45% that ends up in cheese. Retail is the biggest end market for milk products but the ingredient market (B2B) is also large and consumes over a third of milk production.

For Europe as a whole, more raw milk goes to butter production vs. cheese production, but about the same amount of raw milk ends up as drinking milk.

One of the complications of dairy market economics is the complexity of the byproduct ecosystem. Cream production produces skim milk as a by-product. Butter production produces butter milk. Cheeses only incorporate the fat and casein proteins from raw milk (as well as varying amounts of lactose), and produce whey as a by-product. Whey used to be treated as a low value byproduct only suitable for use as a cheap livestock feed, but in recent years, whey proteins have been upcycled into sports nutrition and baked goods ingredients among other uses.

Milk Composition

Cow milk is typically composed of 87% water, 3.5% protein, 4.4% fat, 5.1% lactose and 0.7% ash (2). Milk's protein content is particularly important because milk proteins are easily digested and high in amino acids such as lysine and leucine that are scarcer in plant protein sources. Most PFD companies focus on protein manufacture, although some tackle milk fats.

As shown in the figure above, milk protein is roughly two thirds casein and one third whey proteins. Casein proteins are the primary protein in cheese. Whey proteins are part of the whey byproduct of cheese-making. Casein proteins isolated from raw milk can be further processed for use as food ingredients (e.g. coffee creamers, dairy spreads, baked goods etc.) The global market for raw and processed casein isolates is estimated at ~$3B.

Whey proteins, both in low concentration bulk form and as high concentration protein isolates, are in demand for both their nutritional and therapeutic functions. The global market for raw and processed whey protein isolates is estimated at ~$5B. Individual whey protein isolates have a variety of uses and end markets:

• β-lactoglobulin is is rich in cysteine and leucine amino acids and has high nutritional value.
• α-lactalbumin is the most-abundant protein in human milk and is essential for infant nutrition. Its isolate is priced at $16-27 per kg (2014 data).
• Serum albumin is the most abundant blood protein in human blood and the bovine variant is chemically similar to the human version.
• Lactoferrin performs multiple immune system functions and has benefits for bone growth. It is in high demand as an additive for infant nutrition products as well as neutraceuticals, and commands high prices ($600+ per kg).
• Bovine immunoglobulin isolates are used to treat human gastrointestinal conditions.

Precision Fermentation Technology

Precision fermentation is the process of cultivating gene-engineered or gene-edited microbes at scale to produce useful substances. Genentech's successful use of genetically engineered E. coli to produce human insulin in 1978 is generally seen as the first major success for the technology.

In the food ingredient space, precision fermented chymosin, the major enzyme in rennet, was approved by the US FDA in 1990 (bacterial PF) and 2007 (yeast PF). PF chymosin is now 80-90% of the market and is priced at ~$200 per gallon vs. ~$300 per gallon for animal-sourced chymosin.

Microbial Platforms

While many microbial "platforms" are used for PF, the most common ones are bacterial (predominantly E. coli) and fungal including brewers yeast (S. cerevisiae), various species of blue/green molds (Aspergillus), and a cellulose degrader (T. reesei)). PF microbes are usually fed purified sucrose or dextrose as a feedstock.

The microbial platform is responsible both for translating the desired end-product gene into a raw protein string, as well as shepherding the required "post-translational" modifications. These include folding the protein into the correct shape and attaching phosphate groups (phosphorylation) and/or sugar groups (glycosylation) as well as linking nearby cysteine amino acids within the protein with disulfide bonds.

Phosphorylation allows caseins to transport calcium. Phosphorylation and glycosylation of κ-casein and not other caseins seems to be key to forming the stable macrostructures (micelles) that caseins form in animal milk, which produce their desirable behavior as food ingredients.

Fungal platforms have more capabilities to effect post-translational modifications than bacterial platforms. This makes fungal platforms preferred for PFD, since many dairy proteins are glycosylated/phosphorylated, although engineering them to mimic the exact modifications performed by bovine mammary cells is still a partly resolved technical challenge.

Other microbial platforms are also used for commercial PFD, for example Helaina uses K. phaffii to produce human lactoferrin. And there are yet more microbial platforms that consume non-sugar carbon sources such as cellulose, methane, and even CO?, but these are not common.

Microbial Strain Productivity

Bio-engineers characterize microbial productivity using the TRY factors:

• Titer: the grams per liter of product at the end of production
• Rate: the rate of production in grams of product per gram of biomass per time.
• Yield: the grams per liter of product per gram of feedstock

The cycle time of the process is dictated by the combination of rate and titer. 120 hours is a typical fermentation cycle time, but cycle time can vary widely from that depending on the platform and product.

Of the TRY factors, titer is the one that PF seems to have focused on improving the most. Higher titers mean a lower capital expenditure per unit of product and less water per product unit to be removed in the energy intensive, post-production, "downstream" process.

Initial titer levels for novel proteins at the start of commercialization are generally low. For example, Aro et al. (2023)'s lab-scale port of a single β-lactoglobulin gene using an E.coli platform produced a titer of 1g per liter.

In contrast, titer levels for commercialized PFD proteins are thought to be around 10-30g/l today. This is the range that Lever Venture Capital, a food and ag specialist VC, considers an acceptable titer for a pilot stage PFD company (10). This is 10x more productive than Aro's baseline, but still lower than the ~50g/l considered to be economic breakeven for bulk product (9).

The titer ceiling for PF processes seems to be ~100-200g/l. This titer level has been achieved by microbes producing "homologous" (organism native) proteins (6). Unfortunately, none of the PFD proteins are homologous to either fungal or bacterial microbial platforms, so it is doubtful that PFD can achieve these titer levels anytime soon.

The PF Production Process

Until recently, most PFD companies have used contract manufacturers with processes and process equipment from legacy pharmaceutical and enzyme manufacturing. The PF process is generally divided into three segments:

1. Growth: the starter microbial mass reproduces itself
2. Production: the microbes start producing the target protein (or lipid)
3. Product Reclamation: the target protein/lipid is isolated from the microbial biomass

PF production takes place in massive sterilized stainless steel tanks that are seeded with starter culture, feedstock and growth media and then typically incubated for ~5 days (although incubation times can be as short as a day or as long as several weeks depending on platform and product.)

Most PF tanks operate in batch/fed mode, where additional inputs (feedstock, acid/base, water, control substances etc.) are added during the incubation process to optimize production or to switch from growth to production. For example, in the production of lactoferrin using K. Pfaffii, switching the feedstock from glycerol to methanol switches the microbial platform from growth mode to protein production mode.

Once product reaches target concentrations, the tank is emptied and the product is separated from the residual microbial biomass and usually dried to a powder. The post-process can be energy intensive and costly, responsible for 50-60% of total cost of production (6). Production tanks then have to be sterilized thoroughly before being put back into production.

The waste biomass of spent yeast/bacteria is often used as livestock feed, or as feedstock for anaerobic digestion, but other higher value uses are also being explored. Since the residual biomass contains GMO microbes, regulations can complicate what it is allowed to be used for.

PF Process Challenges

PF process engineers worry about four sources of process challenges: contamination, strain mutation, waste inhibition and product inhibition

• Contamination: wild glucose metabolizers that infiltrate the fermentation tank can either reduce the productivity of the main strain, or if they are pathogenic (e.g. listeria) can produce toxins that make the product unusable. Contamination is avoided by steam sterilization and passing all feedstock through sub-micron filters to catch microbial stowaways.
• Mutations: one of the benefits of a batch process is that you start fresh with a copy of your baseline strain every batch, so there is only a short window for mutated versions of your strain to generate and spread. A challenge with long window continuous processes is that these mutated versions may have longer to generate and accumulate, lowering yield and producing unwanted side-products.
• Waste product inhibition: some PF processes are limited by the accumulation of waste products, which again may limit overall productivity. Systems to eliminate waste product can be added to the process to mitigate this.
• High concentration inhibition: other PF processes are limited by high concentrations of produced protein or biomass. When the ratio of biomass and product reach high enough concentrations, it becomes harder for microbes to access oxygen and feedstock to continue production at maximum rates. Temperature control and dispersion also can become challenging. These issues can be mitigated by aeration and mixing systems, but these can introduce their own issues.

Precision Fermentation Costs

Batch/Fed processes are cost effective at small scales, but at larger scales, Continuous Processes with much longer production cycles (3+ months) become cheaper. A Continuous Process continually adds new feedstock and removes product and waste from fermentation tanks, and is significantly harder to engineer and manage successfully. Multiple startups are developing Continuous Process PF that could be up to 50% cheaper at scale than batch PF.

As mentioned above, PFD costs appear to be high, making it uncompetitive with bulk proteins and lipids produced from animal milk. Synonym, a bioprocess consultant, published a study in 2023 showing the average cost and cost range of new PF facilities, and estimated that the average cost of production for a million liter PF facility was ~ $50 for protein and ~$28 for fats. Since caseins currently wholesale for anywhere from ~$9-16 per kg, it looks like PF needs to reduce costs by ~65-85% from current levels to achieve competitive parity.

That said, there are submarkets where PFD seems to be cost-competitive today. Lactoferrin, in particular, is costly to isolate from animal milk, both because of its fragility and its low concentration (~0.1g per liter). High purity lactoferrin isolate retails for ~$700-1500 per kg today, which has made it an attractive market for PFD startups.

PF Cost Breakdown

There are a plethora of factors that affect PF economics, so any typical cost breakdown should be taken with several grains of salt . That said, I did find it helpful to look at a cost model for an example PF facility to get a feel for the relative importance of feedstock, capital expenditure and operating costs.

Shown below is a cost breakdown produced from Synonym's Scaler model for a 1,000 cubic meter facility producing a PF protein at a 30g per liter titer from dextrose in the US Midwest. The total COGS using this method is ~$26 per kg, assuming a 20 year straight line depreciation of facility costs (excluding financing costs and project equity distributions.)

This example used default values for parameters other than capacity and titer, so the result here is only a very general indication of relative costs. Nevertheless, it does show the relatively small contribution of feedstock costs for mid-titer products. At 30g/l titer, a facility like this could be very cost competitive for lactoferrin production and possibly other protein isolates, but uncompetitive for bulk casein or whey proteins.

Driving Down Costs

1. Increasing Scale

Getting PFD proteins cost competitive with bulk whey and casein from animal milk will require a multi-prong strategy of scaling, process improvement and microbial engineering. Scaling is the most straightforward: more and bigger tanks within the same facility allows better cost spreading for support equipment and labor. Warner Advisors estimates that the scaling factor (cost reduction for every capacity doubling) for PF is roughly 18%. So an 11 million liter facility has roughly half the cost of production as a 1M liter facility (figure below) (7).

If the average production cost of a 1M liter facility is $50 per kg, a hyper-scale facility of 11M liters could reduce that by half, to ~$25 per kg.

2. Improving Strain Productivity

The three TRY factors can all be improved by microbial breeding and engineering. Strain variations can be generated by breeding techniques including traditional selection, induced mutagenesis, and directed evolution, or by explicit gene-splicing and editing. Microbial engineering achieves higher productivity in multiple ways including:

• Adding multiple copies of the production gene to the microbial platform
• Improving support for correct protein folding and other post-translational modifications
• Improving garbage collection of mis-folded proteins
• Reducing the effectiveness of feedback inhibition pathways
• Improving the secretion pathway
• Suppressing energy diversion into unwanted reactions
• Inhibiting activities like protease secretion that break down product proteins in the extracellular space
• And more...

Other techniques for improving titer include:

• Using one microbe to produce multiple desired proteins. This can minimize product inhibition for each protein, while generating higher overall yield. This has been used in amino acid production for acetoin and uridine, where the combined titer reaches 100g/l.
• Co-incubating mutualist strains - particularly where the waste product from one microbe forms the feedstock for a second, reducing the inhibition effects of waste accumulation.

The productivity of many PF products, like lysine, have increased substantially using these techniques over the last twenty years. However, it's not clear how many of these techniques are already in use by PFD startups, since many details of microbial engineering are kept as trade secrets.

3. Reducing Feedstock Costs

Feedstock is not currently the bottleneck cost for PFD. However it's worth noting that dextrose prices in both the US and Europe are meaningfully above world price levels due to trade protections. In the US, import sugar quotas to protect the politically powerful Florida sugar industry have distorted the domestic sugar market for over ninety years (and are the reason that US soft drinks use high fructose syrup made from maize vs. cane sugar).

While dextrose is a easy feedstock to handle, it needs to be sourced at high purity to avoid process contamination, so researchers have used evolutionary forcing to attempt to breed PF strains that can metabolize novel feedstocks with some success.

Methane, for example, is an attractive feedstock because there are relatively few methane metabolizers, so foreign microbes are less likely to contaminate production. Methane metabolizers can also tolerate high temperatures that will kill or deactivate bacterial contaminators.

CO?/H?/O? can also be used as PF feedstocks for some microbial strains, but gas management systems are complex to engineer, and hydrogen systems have to be specifically hardened for safety since hydrogen fires are invisible.

Using other feedstocks such as wood cellulose is an area of active research with some promising results, but I haven't yet found a PFD company talking about this in public materials.

What About Learning Curves?

Many manufacturing processes exhibit predictable learning curves, where production costs reliably reduce by some percentage every time cumulative industry production doubles. For example, learning effects are particularly strong in photovoltaic panels, where unit costs reduce by about 20% for every cumulative doubling.

Given the many opportunities for strain improvement and optimizing production environment variables like pH, temperature and pressure, the range of possible gene promoters, feedstock addition timing, etc. - one would expect there to be strong learning effects in PF production. However, since the industry is relatively new and cost data is hard to access, there has been no published research in this area. There are some suggestions from the biofuels space that there are some learning effects in industrial biotechnology, but the conclusions are tentative.

Relevant Startups

There are at my last count, ~70 companies attacking the PFD opportunity using all combinations of product-type and end market. Almost all startups are using small scale contract manufacturers to produce their first generation products. While this means they are relatively capital light (most PFD startups have 10-100 employees), it also means that they lack the cost benefits of high scale. From scanning LinkedIN insights for many of these companies, it seems that the PFD sector has been treading water over the last year, with many companies downsizing to extend their funding runway, while they reduce production costs and try to establish a customer base. The following companies are just some of the many startups in the space:

PFD Generalists

• Remilk (Israel): $130M+ in funding with multiple trials in partnership with processed food multi-nationals.
• Bon Vivant (France): one of the few companies that added headcount through 2024.

Casein Specialists

• Fooditive (Netherlands): makes all 4 casein variants. The company licensed its technology to the Leprino Group US (the largest maker of pizza cheese in the US) with a goal of 10k tons of production in 2025.
• New Culture (US): concentrates on alpha-casein production

Lactoferrin Specialists

• PFerrinX26(US) - the newest announced lactoferrin specialist, is planning a 200 ton facility in the Midwest.
• TurtleTree (Singapore) - $33M raised, but with unclear traction.
• Helaina (US) - $83M raised for human lactoferrin production

β-Lactoglobulin Specialists

• Perfect Day (U.S) has been the fundraising champion in PFD, with more than $700M raised. It has pursued multiple go to market strategies including own-brand and partnerships with food majors.
• Vivici (Netherlands) is a post-seed company that just commissioned a 75,000 facility to produce at commercial pilot scale in November, 2024.
• Imagindairy (Israel) has raised $28M in funding, and has received strategic investment from Danone. It has announced a partnership with Gingko Bioworks to help develop its casein platform.
• Solar Foods (Finland) is a gas fermentation startup using CO? and hydrogen as feedstocks. It is producing dairy protein as part of the EU Hydrocow project using a Xanthobacter microbial platform.

Supply Chain

• Pow.bio(US) has developed a continuous PF process with anti-contamination and mutation-inhibition capabilities.
• Cauldron (Australia): has developed a continuous fermentation process that works at small production scale
• Triplebar (US): high throughput screening of candidate microbial strains

Conclusions

PFD is a difficult sector to characterize since production unit economics are crucial to success and failure and almost all performance data is non-public. For this article I relied heavily on academic research and industry analyst data and presentations, as well as reading tea-leaves from LinkedIN headcounts and Glassdoor company reviews.

Today PFD seems to be in a twilight zone between failure and success. Current PFD economics are inadequate to displace animal dairy, but based on the evolution of other PF segments, there is a plausible case that a combination of higher strain productivity, higher scale, continuous processing and cheaper downstream technologies, will eventually make PFD directly cost competitive with animal dairy for bulk whey and casein proteins in many applications.

Ultimately, whether this is a 5, 10 or 20 year journey depends on the speed of research innovation and the continued availability of capital.

The ClimateTech Series

1: De-carbonizing Nitrogen Fertilizer

2: Anti-Methane Livestock Vaccines Are Nascent

3: Introduction to Enhanced Geothermal Energy (Fracked Geothermal)

4: Abating Nitrous Oxide Emissions from Agriculture

5: Decarbonizing Concrete is Hard

6: Decarbonizing Cooking Doesn't Matter (Much)

7: Biochar = Cheap & Reliable Carbon Removal

8: Is There a Path to $1/kg Green Hydrogen?

9: Microbial N Fertilizers Do Not Reduce Emissions

10: The Slow and Winding Path to Green Steel

11: Is Enhanced Rock Weathering Effective?

12: Scaled Offshore Wind: Cheap & Getting Cheaper

The Climate Change Impacts Series

1: Climate Change Alters Ecosystems

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