Precision fermentation, growing lab-grown milk and future of dairy farmers
Synthetic milk or lab-grown milk is not a new thing but is gaining traction rapidly and two recent news clips have provided further attention to it:
Both the articles basically talk about fast-paced developments in precision nutrition and how it could become mainstream very soon.
Before moving forward, let me clarify two things:
1. Firstly, it is not ‘synthetic milk’ as claimed by various news outlets but ‘lab-grown milk’ or ‘microbial assisted milk’ as its made through fermentation process with usage ‘synthetic biology’ meaning specific micro-organisms or GMOs are being used to develop it. If we consider this milk as synthetic milk than existing curd, yogurts, cheese or even beer are equally synthetic as the process used is same. More details of the process are explained below.
2. Unlike the fad of plant-based milk and marketing gimmicks played around that, lab-grown milk is very much like cow’s milk in taste, texture as well as nutrition and bio-similar.
P.S.: In entire article, we are using the generic term milk while the fermentation process is used for mainly creating proteins or other derivatives.
What is Precision Fermentation?:
Fermentation has been used in food production for millennia. Ancient civilizations used microbial cultures to preserve foods, create alcoholic beverages, and improve the nutritional value and bioavailability of foods ranging from kimchi to tempeh. Over the past century, the role of fermentation has expanded far beyond its historical usage to a much broader range of applications.
Fermentation now spans industrial chemistry, biomaterials, therapeutics and medicine, fuels, and advanced food ingredients. The suite of tools developed through fermentation’s evolution is now poised to revolutionize the food sector by accelerating the rise of alternative proteins.
The term “fermentation” carries distinct meanings across different disciplines. Within biology, it refers to a specific metabolic pathway used to generate energy in the absence of oxygen. Within the alternative protein industry, fermentation is used in three primary ways:
1. Traditional fermentation uses intact live microorganisms to modulate and process plant-derived ingredients.
Traditional fermentation results in products with unique flavor and nutritional profiles and modified texture. Examples are using the fungus Rhizopus to ferment soybeans into tempeh, as well as using various lactic acid bacteria to produce cheese and yogurt. There are also more modern renditions of this concept, such as MycoTechnology’s fermentation of plant-based proteins to improve flavor and functionality.
2. Biomass fermentation leverages the fast growth and high protein content of many microorganisms to efficiently produce large quantities of protein.
The microbial biomass itself can serve as an ingredient, with the cells intact or minimally processed — for example, the cells can be broken open to improve digestibility or enrich for even higher protein content.
This biomass serves as the main ingredient of a food product or as one of several primary ingredients in a blend. Examples of biomass fermentation are Quorn’s and Meati’s use of filamentous fungi as the base for their products.
3. Precision fermentation uses microbial hosts as “cell factories” for producing specific functional ingredients.
These ingredients typically require greater purity than the primary protein ingredients and are incorporated at much lower levels. These functional ingredients can improve sensory characteristics and functional attributes of plant-based products or cultivated meat.
Precision fermentation can produce enzymes, flavoring agents, vitamins, natural pigments, and fats. Examples include Perfect Day’s dairy proteins, Clara Foods’ egg proteins, and Impossible Foods’ heme protein.
Microbial- or precision fermentation is a technology that has been widely used in different industries for decades. It is known to be very scalable using different microbes to produce ingredients at large volumes. Precision fermentation will continue to play a significant role in the production of next generation food ingredients.
The precision fermentation process is a game-changer for food manufacturers. DNA sequences of functional proteins are encoded onto microorganisms, these microbial hosts act as ‘factories’ in which cells capable of producing very precise ingredients duplicate very quickly. Precision fermentation provides a real viable solution for large-scale production of specific functional ingredients to support the manufacture of different foods.
Alternative proteins themselves can be produced through precision fermentation, however there are also a range of supporting ingredients required for food manufacture that can be produced at large scale through precision fermentation. Moving away from animal-derived products doesn’t stop at the final food product itself. The requirement for animal-origin-free growth factors are in demand to support the production of cell-based meats. Growth factors play a key role in culturing cells, stimulating the growth of specific tissues and signalling cell differentiation. Microbial/precision fermentation improves the availability of growth factors and allows their cost to be driven down ultimately making the production of cell-based meats a more viable alternative to traditional food proteins.
Traditionally, many food processes have used animal-derived enzymes to modify ingredients, for example rennet in cheese making, or pancreatin in producing infant formulas and modified whey protein powders. Consumer trends for vegetarian products as well as Kosher and Halal certified products has led to a shift by food manufacturers to use processing aids meeting consumer demands and trends. The process of precision fermentation allows the sequence of traditional animal-derived enzymes to be encoded into microbes and produced at scale to replicate the same enzymatic activities. Producing microbial enzymes through fermentation significantly improves the availability and continuity of supply in addition to minimising cost fluctuations and meeting consumer demands whilst not compromising on enzyme functionality.
Supply security is another considered reason why manufacturers seek the manufacture of preservatives through precision fermentation. Lysozyme is widely used as a preservative in many foods, however being derived from egg whites brings with it insecure supply like other naturally sourced products. Further in this example, egg-white derived lysozyme is considered an allergen. Precision fermentation would enable the DNA of natural lysozyme to be encoded into microbial hosts to produce real proteins with almost identical functionality and anti-microbial qualities of the natural lysozyme for use as a preservative with improved product supply but without the allergenicity associated with its natural counterpart.
As the food industry focusses on functional foods, manufacturers are increasingly looking at the use of peptides in food products. Peptides are short chains of amino acids from a wide range of sources from eggs and milk to cereal grains. The amino acid composition of the peptide determines its specific activity such as preventing oxidation and microbial degradation and spoilage of food. Many bioactive peptides are encrypted in a natural protein structure which must be released to harness its benefits. Processing proteins to release the peptide can cause difficulties, as different processing technologies can impair the peptide’s activity during this process. Precision fermentation allows manufacturers to produce peptides at scale that mimic the activity and function of naturally sourced peptides.
Precision fermentation plays a bigger role in your foods than you realised. As a technology capable of reducing costs whilst delivering safe and high-quality scalable proteins sustainably, precision fermentation opens the doors to many exciting developments in the food industry.
How precision fermentation works?
Traditional fermentation processes rely on microbial cells (yeast, fungi) and anaerobic (oxygen-free) conditions to convert ingredients into end-products with unique texture or flavour properties such as yoghurt, bread, cheese, tempeh, and alcoholic beverages.
Biomass fermentation, on the other hand, makes use of the nutritional qualities of fungal mycelium, and the branching thread-like fibres that typically form the vegetative part of a fungus. Mycelium are cultivated in large tanks, with sugar and other nutrients added to trigger growth. The mycelium is harvested, then cut and flavoured to produce alternative protein products (mycoprotein). Fungal mycelia offer high levels of protein as well as fibre, vitamins, minerals, and can be used directly as an ingredient, without the need to extract and purify the protein.
One example is the mycoprotein derived from the fungus fusarium venenatum which was pioneered in the late 1960s and has been sold under the brand Quorn since 1985. Since then, other mycoprotein start-ups have emerged around the globe, such as Fable Foods (Australia), Meati, Prime Roots and Nature’s Fynd (USA), Mushlabs (Germany), and Kinoko-Tech (Israel). Nature’s Fynd Fy protein, for example, is derived from a different fusarium strain flavolapis, discovered from the hot springs of Yellowstone National Park. Products such as Fy protein can serve as an ingredient for dairy-free or meat-free foods.
Today, precision fermentation is being harnessed to synthesise compounds that would otherwise be too expensive and/ or complicated to harvest from their natural sources. While traditional and biomass fermentation involve propagation of microbial cells without any genetic modification, PF relies on reprogramming microbes to produce specific, customised (recombinant) molecules that can serve as new food ingredients.
By introducing the genetic information that codes for specific proteins into the microbial genome, cells can be programmed to act as highly efficient cellular factories that can grow on a variety of carbon sources and deliver desired outputs, which are typically proteins equivalent to those found in nature.
The novel products obtained via precision fermentation technology can enhance consumer products by improving taste, texture, or other functional aspects to accommodate consumers’ preferences and sustainability concerns.
A well-known historical example of a high-value food protein derived from precision fermentation is chymosin, the major enzyme in calf rennet used during cheesemaking. In fact, by 2006 fermentation-derived chymosin occupied as much as 80% of the global market share for rennet.
Precision
fermentation relies on the production of novel proteins or protein ingredients
by:
1. Growing microbes on a cheap carbon source (feedstock) such as sugar
2. The microbial cells themselves are genetically modified to produce the
desired protein in high quantities. Typically, this engineering step requires
multiple cycles where required genetic changes are predicted, designed and
introduced into the DNA of the cell. This is followed by testing for the
presence of the target protein, validation of the desired food property and
further genetic improvements to increase product quantity and quality. This
rapid and often complex ‘design-build-test-learn’ engineering process is
defined as ‘synthetic biology’ and happens in small reactors in the lab
3. The next step is a gradual scaling-up of the culture volumes from lab (tens
of litres) to commercial scale (order of hundred thousand litres)
4. Depending on the application, the proteins are extracted, purified and
combined (formulated) together with other ingredients into,
5. The final food product.
Why Precision Fermentation?
To feed the global population of the future, we will need to produce food at a greater scale, and more sustainably, than today. To meet that gap, we will need to derive even more protein from traditional sources (meat, dairy, eggs, seafood, plants) in addition to protein from emerging but complementary sources (yeast, fungi, algae, insects).
Precision fermentation is a relatively new food technology that is rapidly entering the mainstream. Products such as milk protein, animal fats, collagen, honey, lobster, egg whites and more are receiving hundreds of millions of investor dollars. They are being rapidly commercialized for the mass market without the raising and killing of animals. These products are being marketed to a young consumer base that wants sustainable, climate-friendly foods that buck the system and promise a better tomorrow.
Precision fermentation challenges and opportunities
The opportunity of producing tailored food ingredients by PF has not gone unnoticed to investors with Companies like Nature’s Fynd, Remilk, Motif Foodworks and Perfect Day receiving millions of dollars in funding.
Despite the growing interest, several challenges remain for this emerging industry. Most precision fermentation start-ups are still at a relatively early stage. Fermentation infrastructure with the capacity to operate at scale is also limited, highlighting the urgent need for investment in larger scale fermentation and downstream processing facilities.
Early implementation of techno-economic analyses is needed to assess overall economic viability during scale-up and to identify critical factors that determine the cost of goods. Similarly, sustainability and carbon footprint claims related to specific precision fermentation production processes will need to be supported by rigorous independent life cycle analysis.
Regulatory approval frameworks with regards to synthetic biology and precision fermentation are currently being revised in many jurisdictions, to keep up with technological innovations such as genome editing.
Consumer perceptions related to novel precision fermentation derived food products and appropriate labelling will require social licence to ensure continued trust and transparency.
Future research will focus on improving the overall cost effectiveness of PF processes to achieve higher product yields. Improvements in cellular secretion machinery will simplify downstream purification and, in turn, improve capital utilisation and lower costs.
Novel naturally occurring and under-utilised microbes or next-generation microbial strains will be investigated for their ability to thrive on abundant and cost-effective feedstocks, to replace refined sugar by various (food) waste streams and even CO2 (eg. Air Protein).
New artificial intelligence/machine learning (AI/ML) algorithms will offer the opportunity to drastically speed up the engineering of new microbial production strains by relying on computer models that can simulate the effect of specific genetic changes on overall cell behaviour and composition (metabolism).
Advances in AI/ML are also breaking ground in the prediction of ingredient combinations that result in new flavours (NotCo), the engineering of sweeteners with novel properties via computational protein design (Amai Proteins), and screening for novel protein functionalities using large food-safe protein databases (Protera).
Continuing innovation in bioreactor redesign tailored for food-grade fermentation is required and these systems will need to be powered by renewable energy resources to deliver their full impact potential.
Minimising purification/processing and maximising value extraction from left-over microbial biomass through the delivery of co-products during downstream processing will improve the overall economics of precision fermentation technology.
What can go against Precision Fermentation?
Much of the marketing and fundraising for such products revolves around being significantly less harmful to the climate than cattle rearing. Precision fermentation requires large investments in concrete, steel, plastic and fossil-fuel dependent electric utilities to maintain the particular environmental settings necessary for the microorganisms to thrive. If the sector wishes to have a significant impact on consumption, they will require the buildout of thousands of fermentation tanks and dozens, if not hundreds of facilities. How will this resource use impact communities already dealing with the environmental racism and colonialism inherent in mining, tech manufacturing and waste disposal?
What kind of testing has been done to understand the potential environmental impact for if and/or when the microbes escape the confines of a fermentation plant, particularly as the technology scales? Can they survive and interact in the variable conditions and ecosystems that exist in the wild? Since some of these organisms are derived from strains that can live and thrive well outdoors, what are the environmental risks? Cattle farms have long been linked to the spread of pathogens and pandemics, so will precision fermentation reduce these risks or create new ones?
The biggest set of questions here revolves around ownership, governance and social equity considerations. Just about all of this new food technology is heavily funded by tech oligarchs, venture capitalists, or the occasional celebrity. The investor model here is very Silicon Valley: identify a particular market sector or category and its sales potential, fund the company to offset large losses as it scales, and compete aggressively with the goal of cornering this market as a monopoly or a duopoly. The investors throwing billions of dollars at such enterprises are not altruists, even if some are motivated by animal rights or climate change. They have a fiduciary duty to their shareholders and are betting on the potentially enormous upside in the enclosure and market domination of whole commodity groups and categories.
So, is the value of the enterprise in the finished product, as either a raw material, ingredient or CPG item? Or is it in the process and techniques or the microorganisms themselves? Who holds the patents or intellectual properties? How much of this technology is open sourced? What will be the implications for a single company to own the formula for milk, honey or eggs?
The life cycle research around precision fermentation shows extremely favorable positioning against cattle farms that exacerbate climate change. But these studies should also consider the growing category of humanely raised, carbon neutral, Biodynamic and Regenerative Organic dairy products. Nor do they compare to the burgeoning sector of agro-ecologically produced foods that provide impressive yields, integrate humanely raised livestock, demand land reform and require greater social equity.
Will Precision fermentation outperform cow & what would happen to dairy farmers?
London based independent think-tank RethinkX is predicting the most consequential disruption of food & agriculture in history. According to RethinkX, precision fermentation is driving down cost & driving up the quality of modern proteins.
RethinkX in its recent report opines that disruption of dairy sector by precision fermentation would happen by replacing just 3.3% of milk’s contents. The small percentage of key functional proteins is all that need to be substituted by precision fermentation derived ingredients to disrupt the industry. This would be an ingredients led disruption in business and does not rely on change in consumer behaviour.
The demand is there, report says. “Nestle, for example, buys almost 2% of global dairy production,” adding that “Quorn also uses protein in their products.” As is the current supply: “We know that about 35% of dairy protein in the US ends up in the B2B market and about 70% of the New Zealand dairy market is made into solids and exported.”
The implication is that industrial cattle farming, and all livestock farming, will be obsolete by 2035, it reported. “Precision fermentation is going to outperform the cow.”
Looking beyond the collapse of the dairy sector, precision fermentation technology has the potential to transform and decentralise the food system. “Anywhere you can brew beer, you can make food,” said report, suggesting that today’s centralised food systems could be transformed into local, network-focused production.
The implications of precision fermentation are therefore ‘massive’ and ‘profound’, spanning environmental, economic, social, investment, and geopolitical sectors.
In the not-so-distant future, we may see fermentation tanks incorporated into the urban landscape. Food costs are also predicted to drop. RethinkX predicts fermented foods will be priced at least 50%, and as much as 80%, lower than the animal products they replace.
Its environmental benefits are another key argument for precision fermentation technology. These ingredients will be up to 100 times more land efficient, 10-25 times more feedstock efficient, 20 times more time efficient, and 10 times more water efficient than industrial livestock, noted the think tank. “They will also produce an order of magnitude less waste.”
Conclusion
Whether it makes sense for the food industry to replace one capital and resource intensive system for another, of course without animal usage and seemingly more climate friendly? Precision fermentation, or synthetic biology, is a clever food-tech. It will hopefully be far less destructive than conventional agriculture. With the potential to produce required nutrition with similar taste, texture, flavour & nutrition at much lesser cost & lower environment impact, this is bound to gain traction.
Food Companies must not miss this bus as the technology is both disruptive & promising!
Source: Good Food Institute, RethinkX, CSIRO, Forbes
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