Precision fermentation is a production process in which specific biological molecules are manufactured using microorganisms. It can be used to produce food ingredients that are conventionally sourced from animals and plants, including proteins, lipids, carbohydrates, and other metabolites. Bacteria, yeast, or other cell types produce large quantities of a specific compound which is then extracted and purified from the fermentation broth or cell lysate. For example, milk or egg proteins, dairy fats, functional oligosaccharides, flavour and colour compounds or vitamins. Precision fermentation is different from other forms of fermentation used in the food industry because it produces a single target molecule with high precision and purity. In other approaches like traditional fermentation or biomass fermentation, the product contains a mix of fermentation outputs, biomass, and substrates. This precision is achieved by optimising both the culture conditions and the microbial strains used in the process. While it is possible to use organisms that naturally produce useful ingredients, in some cases engineered strains are developed using adaptive laboratory evolution, mutagenesis, or by introducing specific gene sequences. The purification and extraction process ensures that genetically engineered organisms are not present in any final products. Although the term "precision fermentation" is relatively new, the underlying technologies have been used since the 1980s. Proteins like insulin for diabetes treatment or chymosin (rennet) for cheese manufacturing have been produced by these techniques for decades and are well integrated in the market. Precision fermentation incorporates genetic tools, synthetic biology approaches and strain engineering techniques, and it has a promising role in future biobased food production systems. It is expected to become an essential technology in a global shift towards more sustainable food systems, in the context of climate change and in areas where the availability of agricultural land is limited.
Principles of precision fermentation
A fermentation bioprocess encompasses all the steps necessary to transform a raw feedstock into the desired molecule of interest, including the choice of the microbial strain that will be performing the transformation and the conditions in which it will be growing.
Feedstocks Feedstocks generally refer to the predominant raw materials used as a source of carbon, nitrogen, and energy for microorganisms to grow and produce end products. The choice of feedstocks for precision fermentation is critical, as it significantly impacts the cost and sustainability of the products.
First generation sugars. Currently, the majority of precision fermentation processes are conducted using refined glucose derived from food crops. These sugars support robust microbial growth and are safe for use in food production; however, they have drawbacks such as higher costs and competition with the food supply. Second generation sugars. These are fermentable sugars obtained from non-food, lignocellulosic biomass such as agricultural residues. This reduces competition with food production and improves the sustainability of fermentation-based products. C1 feedstocks. Carbon dioxide, methane, formate, and methanol are considered highly sustainable for microbial growth and product synthesis, as they help minimise environmental impact. Although significant achievements have been made in this field, major challenges still remain for the effective utilisation of C1 feedstocks in mainstream manufacturing processes. Food industry sidestreams. Food manufacturing wastewaters or byproducts from food processing can be used as inexpensive feedstocks in a circular bioeconomy approach and can be converted into fermentable sugars to serve as substrates for precision fermentation.
Cell factories A cell factory is a biological system (microorganisms, plant cells, or mammalian cells) that transform substrates into high-value biological products, such as proteins, enzymes, vitamins, pharmaceuticals and biomaterials under controlled conditions. Microbial strains commonly used include Bacillus subtilis, Corynebacterium glutamicum, Escherichia coli, Komagataella phaffii, Saccharomyces cerevisiae, and Yarrowia lipolytica. Each of these hosts possesses unique genetic and metabolic characteristics that make them suitable for defined production purposes in precision fermentation. The selection of a microbial host is based on various factors, including the presence of native biosynthetic pathways for the desired product, the capacity for efficient expression of heterologous pathways, the safety profile of the organism, and its compatibility with different cultivation conditions.
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