Precision fermentation is a well-established technology that has been used successfully for the production of high-value proteins ($100/kg and above), such as those used in pharmaceuticals (e.g. insulin) or as food enzymes (e.g. rennet). However, in recent years, precision fermentation has taken on a new and exciting role in the field of cellular agriculture.
The proteins produced through this technology can precisely match the functional and nutritional properties of animal-based counterparts. For example, precision fermentation-derived egg proteins can be used to foam or aerate products such as whipped cream, meringues, and marshmallows, whilst providing the same protein content as a conventional egg. This represents a major breakthrough for the food industry, as it offers a way to produce novel food alternatives that are authentic replicas of animal-derived products, without any of the ethical or environmental concerns associated with traditional animal agriculture.
Although precision fermentation for cellular agriculture shares some similarities with conventional precision fermentation, it also presents unique challenges. One such challenge is the ability to produce low-value molecules that can be made at scale while remaining economically viable.
Therefore, in this article, we will provide an overview of the technology, including the parallels and key differences between its conventional and novel food applications. By doing so, we aim to highlight opportunities for continued innovation and process optimization so that we can accelerate the development of precision fermentation and cellular agriculture to transform the future of food.
Cellular agriculture is a field that involves using cell cultures to produce agricultural products, such as meat, dairy, and eggs, that would otherwise typically be obtained from animals. The field has two primary branches: cultivated meat and precision fermentation.
Cultivated meat, or lab-grown meat, involves the production of a complete replica of an animal-based agricultural product and is still in the early stages of research and development. In contrast, precision fermentation cellular agriculture builds upon an established production platform to produce authentic animal proteins and products using cell cultures, making it a natural and promising technology for the development of animal-free alternatives.
While cellular agriculture is now widely being explored to create replicas of animal-derived proteins and products, the technology has evolved to the point where it can create entirely new products that were previously impossible or impractical to produce.
By utilizing cell cultures and precision fermentation techniques, it is possible to design and manufacture products with specific properties, such as improved texture or nutritional content, that cannot be achieved in conventional animal-derived products. This opens up new possibilities for the development of sustainable, healthy, and innovative food products that are not limited by the constraints of traditional animal agriculture.
Precision fermentation products currently available on the market are typically high-value molecules such as pharmaceuticals or enzymes. The products required for the purposes of cellular agriculture, however, are typically low-value structural and storage proteins. One of the main challenges for precision fermentation and cellular agriculture is to ensure that manufacturing costs are low enough to make these methods economically viable.
Advancements in genetic engineering and computational biology have enabled the production of complex ingredients at a lower cost, including various proteins, fats, and enzymes. Despite this progress, the price point for precision fermentation is not yet competitive with typical food ingredients, although it is predicted to change soon. For example, some companies (e.g. New Culture) and research groups are forecasting the production of cost-competitive cellular agriculture proteins, such as casein and whey, before 2025.
Examples of precision fermentation-derived ingredients currently under development include milk proteins, egg proteins, and collagen. The majority of companies focus on applications within the dairy food segment; as of the second quarter of 2023, 41 of the 95 companies involved in precision fermentation on Bright Green Partners’ Protein Directory are focused on dairy products.
The focus on dairy products in precision fermentation and cellular agriculture is due to a variety of reasons. First, the use of this technology allows for the creation of lactose-free dairy products, which provide an allergen solution for those who are lactose intolerant. This is a significant advantage over traditional animal-derived dairy products, which have to undergo expensive processing to remove lactose.
Dairy products also have a wide range of applications, such as cheese, ice cream, sports drinks, spreads, and more. This makes them an attractive target for ingredient developers who are looking to create animal-free alternatives that are indistinguishable from their traditional counterparts. Furthermore, a significant portion of dairy (one-third) is sold as an ingredient, which creates a large market opportunity for precision fermentation companies focused on dairy products.
The corporate interest in precision fermentation-derived dairy reflects both the market opportunities and the technical advantages that this technology can offer in this particular sector. However, it's worth noting that precision fermentation has the potential to create animal-free alternatives for a wide range of products, beyond just dairy, and the field is rapidly evolving with new companies and applications emerging all the time.
When it comes to animal products, it's crucial to determine which among dozens of molecules are the most important to include in the final formulation to achieve equivalent taste and nutrition. Selecting the right target for product development requires balancing the desired functionality with the research and development effort and costs of production. Target selection is evolving rapidly thanks to recent advancements in computational biology, such as Triplebar or Google Deepmind's Alphafold.
Besides the forecasted price parity, one of the significant advantages of precision fermentation and cellular agriculture is the precision of modern genetic tools. The development of more precise technologies has made it significantly easier to develop host strains achieving economically viable yield, titer, and productivity, even for lower-value animal proteins suitable for food applications.
The process for producing cellular agriculture proteins is essentially the same as any microbial protein production process but with a varying degree of purification depending on the intended end-use application. Compared to the production of therapeutic antibodies, for example, cellular agriculture proteins require less stringent purification processes.
Generally, a moderate degree of purification should suffice, although the extent of what’s required may depend on whether the presence of other cell components would have an impact on the intended application. Lower purification standards would also reduce production costs.
Despite the lower degree of purification, the process itself poses a significant challenge. Instead of being naturally secreted, many cellular agriculture proteins accumulate inside the host cell. To purify these proteins, it may be necessary to break down the host cell, increasing the likelihood of contamination from cellular debris.
To circumnavigate this challenge, and transform it into an advantage, manufacturers could explore a microbial host cell that provides benefits to an end product in and of itself. For example, a strain of yeast that contributes desirable sensory attributes could be used to express the protein of interest, which would eliminate the need for purification and improve the economics of the process.
Manufacturers will also need to consider the specific novel food regulations pertaining to their proteins, which will determine the methods undertaken to ensure safety and efficacy.
Cellular agriculture proteins are distinct from conventional precision fermentation-derived proteins in that they are often storage or structural proteins rather than enzymes. While this means that the proteins are unlikely to cause undesirable activity within the host cells and end products, it does present the issue of incorrect protein folding, preventing the protein from functioning as it should. Storage and structural proteins tend to be larger, more complex, and difficult to assemble in a non-native host cell.
Precision fermentation and cellular agriculture hold tremendous potential for the food industry, but there are still challenges to overcome. With continued research and development, we can unlock the full potential of these technologies and create a more sustainable and equitable food system.
At Bright Green Partners, we specialize in providing comprehensive support for the alternative protein industry, including insights and guidance on the latest developments and opportunities in precision fermentation and cellular agriculture. Contact us today to gain clarity and unlock the full potential of your cellular agriculture proteins.