Deep Dive: We Need to Talk About Precision Fermentation
Deep Dive: We Need to Talk About Precision Fermentation
The technology stands to transform food and agriculture by the end of the decade with incredible progress already well underway.
Precision Fermentation has been around for a while. In 1978, Genentech engineered the Escherichia coli bacterium to produce the first human insulin protein. Up until then insulin was obtained by harvesting the pancreas of pigs and cows: around 50,000 for a single kilogram of insulin. Thankfully this is no longer the case. 99% of global insulin is now produced by microbes, and yet, very few of us are even aware of this groundbreaking technology. One that could produce almost anything, and much the same way we make beer.
A little history -
Precision Fermentation builds on the ancient practice of fermentation which uses microorganisms and sugar to convert an input into a slightly different output, like turning milk into yoghurt or wort into beer. However, Precision Fermentation takes this process further by instructing microorganisms to produce very specific compounds of interest. The food industry has embraced this technology with both hands: 90% of rennet, almost 100% of Vitamin B12, and the vast majority of Vanillin, Betalains and yeast extract currently on the market is made using Precision Fermentation. It’s heavily used by pharmaceuticals too, to produce not only insulin but also human growth hormone (HGH), Penicillin and the Hepatitis-B vaccine. And these examples barely scratch the surface, Precision Fermentation has the potential to produce nearly any complex organic molecule.
Got Milk? -
While the name L1 Dominette 01449 may seem unremarkable, this brown and white Hereford cow is significant. Born on April 14th, 2001, her entire genome was sequenced at the Baylor College of Medicine Human Genome Sequencing Center by April 24th, 2009. The team of researchers created a comprehensive digital record of all her genes, approximately 22,000 in total. Among these genes, one is responsible for milk production, and thanks to Dominette, we now know exactly where to find it and how to recreate it. By inserting the gene encoding milk proteins into a microorganism of choice using genetic engineering techniques (such as CRISPR), scientists can coax the organism to express those proteins.
Whey and casein are the main proteins in milk and together account for a mere 3.3% of milk's overall composition. The rest is 87.7% water, 4.9% sugar (mainly lactose), 3.4% fats, and 0.7% vitamins and minerals. Because the key proteins that make milk commercially valuable comprise only a small fraction and can be produced far more efficiently and sustainably through Precision Fermentation, the dairy industry finds itself on the brink of a major disruption. Such a shift is not just a possibility—it's already happening. Perfect Day, arguably the market leader in Precision Fermentation, raised $90 million in a pre-series E financing round in January whilst industry incumbents such as Fonterra are enthusiastically adopting the technology .
An important clarification to make is that Precision Fermentation relies on “strain engineering”, where the microbial strain is genetically modified, and not the final product. The final product i.e. the target protein, is exactly the same as what some of us would call the “natural” version of the protein, in this example the whey and casein originating from the cow.
Similar to traditional fermentation, microorganisms require energy in the form of sugar in order to produce the target proteins. Sugar-based foods like sugarcane or corn sugars undergo various treatments before they are turned into the nutrient-rich medium which fills fermentation tanks. Here, the organisms will consume the sugars, grow, proliferate and express the target proteins. A subsequent filtration and purification process separates the target proteins from the microbes and the nutrient medium, isolating an extremely pure version of the protein.
A world of possibilities -
Over the years, publicly available DNA-sequence databases have grown significantly, thanks to scientific contributions. The DNA sequences for many genes and organisms are now widely accessible, meaning we are far from limited to milk. We can, for example, insert genes responsible for making honey, egg-white, cocoa or coffee. The latter two being commodities whose costs have recently skyrocketed because of our changing climate and the resulting shortages. We can also produce non-food-products such fabric dyes, leather, silk and even collagen from a Mastodon. And all of these, at the fraction of the environmental impact of conventional practices.
Some companies such as Nourish Ingredients are positioning themselves as suppliers in a Business to Business (B2B) model and are using Precision Fermentation to produce animal fats, the main ingredient giving meat its flavour. When combined with plant-based proteins in products like burgers, these fats enhance the overall sensory experience and often rival their animal-based counterparts to provide an increasingly satisfying option for consumers.
Another example is the Impossible Burger. If you’ve ever had the pleasure of tasting it, you’ll remember the distinct meaty flavour it’s known for. That flavour comes from Heme, an iron-containing molecule and a primary component of Haemoglobin i.e blood, which the Impossible Burger produces via Precision Fermentation thanks to the yeast Pichia Patoris.
Innovation wanted -
Whilst Precision Fermentation has been around for decades it is a technology still very much in its infancy with enormous potential for planet, health and animals. Being so young is very expensive and many aspects of the bioprocess are in need of optimization to reach cost parity with traditional products and capture significant market share. Where cost parity has already been achieved for pharmaceuticals which command high costs per unit, it’s a different story entirely for heavily subsidised, low-cost food products.
The industry needs to focus on innovation in infrastructure, technology, and financing models to make biomanufacturing scalable and economically viable. Modular facility designs and automation can be valuable tools here. New financial models and partnerships are also crucial in overcoming economic barriers and accelerating growth in the sector. A common model is partnerships with industry titans, such as Inbev or AGM. Known as Contract Manufacturing Organisations (CMOs), these are organisations that own the infrastructure and provide manufacturing services to companies developing new biotechnology products . This saves startups the need to raise, often prohibitive, capital to build infrastructure before even starting commercial production.
To catalyse the move to a far less destructive food system, governments should also reallocate subsidies from the fundamentally inefficient sector of animal agriculture to the far more sustainable sector of Precision Fermentation. At the very least it should provide grants, loans and guarantees.
Important work is happening in optimising strain engineering: what microorganisms are best suited to which protein? How can we increase their protein yield? Researchers are also looking at how to optimise taste profiles, for products that could be even tastier than the conventional products we’re used to.
To save on production costs, the quality of the nutrient medium could be dropped from pharmaceutical grade to food grade. Some companies are looking at ways to recycle their nutrient medium. Others are looking at using raw ingredients and side streams from other industries such as agriculture. For example, German startups ProteinDistillery and Infinite Roots, which raised €15M and €53M, respectively, are planning to expand their mycoprotein production by using brewery by-products.
Inevitably Precision Fermentation will create waste products in the form of microbial biomass and probably in great quantities as the sector industrialises. Perhaps this could be used as fertiliser or in the manufacturing of bioplastics or as an energy source or even as food ingredients. The possibilities for a circular economy are enormous and we need to get creative. To grow the industry we also need to widen the talent pool, and attract professionals from all backgrounds.
Looking ahead -
To quote RethinkX we are entering the age of a second domestication of plants and animals. The first domestication allowed us to master macro-organisms such as cows and sheep for our food. This second domestication is allowing us to harness microorganisms for a much more sustainable, ethical and healthier food system. One that can return 70% of the land we currently use for agriculture to nature. An outcome that would greatly improve biodiversity, enhance our experience of the natural world and help combat the most severe impacts of climate change.
Some technologists predict that our current food system will be replaced by a Food-as-Software (FaS) model, one where foods engineered by scientists at a molecular level will be uploaded to databases that can be accessed by food designers anywhere in the world. This could mean milk without the lactose, eggs without the cholesterol, rice fortified in vitamins and minerals, beans with complete protein profiles or foods we can’t even begin to imagine yet, all produced anywhere we can brew beer. This would drastically improve food security and democratise access to nutritious food. Precision Fermentation offers the opportunity for a truly distributed and decentralised food system, one that can guarantee a future where we can all eat a nutritious diet. Not one where the price of chocolate and coffee is greater than gold and reserved for a select few.
Sources:
Precision Fermentation Perfected: Strain Engineering
How we Get Microflora to Create Sustainable Protein - Perfect Day
Precision Fermentation Home Page
The science of fermentation (2024) | GFI
Precision fermentation’s capacity craze: Have we lost the plot? | TechCrunch