Transition from fermentation to precision fermentation: Role in sustainable food system

Highlights

• •Historical milestones from traditional practices to precision fermentation (PF) was reviewed.
• •Applications of traditional fermentation in food and role of fermented foods in health.
• •Role of precision fermentation in food and beyond food production.
• •Industry leaders and examples of products addressing these global challenges was also discussed.
• •Role of PF in addressing climate change, resource scarcity, and resilient food systems was also discussed.

Abstract

Fermentation has been used for centuries to preserve foods and enhance their sensory, nutritional, medicinal, and commercial qualities, as demonstrated by products such as bread, beer, yogurt, and cheese. Since the 1970s, advances in genetic engineering, together with recent developments in synthetic biology, have transformed fermentation from a largely empirical practice into a highly controlled and precise technological platform. This transition has enabled the targeted biosynthesis of high-value compounds, including specific proteins, enzymes, polysaccharides, and other functional ingredients with broad applications in food and health sectors. This review examines the evolution from traditional fermentation to precision fermentation, highlighting the key technological innovations driving this shift. It critically evaluates the role of precision fermentation in advancing sustainable food production and human health, while addressing its environmental and economic feasibility, compatibility with existing food systems, and practical implementation challenges. The increasing significance of precision fermentation presents important opportunities to enhance global nutrition, support human well-being, and contribute to the development of resilient and sustainable food systems.

Graphical abstract

1. Introduction

Fermentation has been the cornerstone of human civilization for centuries, transforming simple ingredients into diverse nutritious foods like bread, beer, yogurt, and cheese [1]. This ancient process, driven by the metabolic activities of microorganisms, not only preserved food but also enriched it with unique flavors and health benefits [2]. Initially, fermentation was simply described as a natural metabolic process involving microorganisms like bacteria, yeast, and fungi, converting organic compounds into other substances [3]. But the definition of fermentation has changed over time and has become broader. According to Boukid et al., [4], fermentation entails metabolic processes by which bacteria, yeast, fungi, or algae use carbohydrate sources to effect changes in substrates to be used for consumption, food additives, or become the source of food or supplements themselves. Traditional fermentation has been an essential part of human culture for centuries, turning basic raw materials into healthy, marketable, and delicious products such as bread, beer, or cheese [5]. Over the last few decades, great changes have been transforming fermentation techniques into precision fermentation underlined by modern biotechnology using genetically engineered microorganisms to synthesize proteins, enzymes, and other bioactive compounds [1]. Precision fermentation is a novel and emerging method of biotechnology comprising product purification, microbial strain and process optimization techniques to synthesize specific ingredients like target proteins, enzymes, vitamins, and polysaccharides with high precision and efficiency [6]. Even though traditional fermentation depends on the spontaneous effect of microbial activities to metabolize food, precision fermentation leads to the tested synthesis of molecules of interest [7]. Precision fermentation methods recreate various proteins, such as those found in animal products, without necessarily using the animal. These unconventional fermentation methods are applied to manufacture foods like animal-free dairy, eggs, collagen, meat alternatives, probiotics and steviol glycosides through the actions of certain microorganisms, which are at the forefront of food innovation [8].

Traditional fermentation techniques, precision fermentation is cultivated to produce valued products, offering sustainable, ethical, and healthier food alternatives or resource-intensive food production methods [9]. On the contrary, conventional fermentation does not apply genetic technologies to optimize microbial strains and operation efficiencies [10]. Eastham and Lemon affirmed the superiority of precision fermentation over traditional fermentation methods in sustainable, efficient, specific, product recovery or yield in food industries, favouring large-scale production [11]. Even though fermentation is an important phenomenon in contemporary food production in many parts of the world, precision fermentation might offer better solutions to conventional animal husbandry, and challenges of food security, accessibility, safety, affordability, supply chain vulnerability, antibiotic resistance, and commodification [12,7,13]. It enhances the nutritional values of plant-based proteins, requires less land and water, and reduces ecological footprints like gas emissions, carbon, and waste than conventional systems [8]. With the world’s population on the rise, precision fermentation is a more credible choice in diversifying food and food products to meet the dietary demands of the growing population, expanding the range of protein diet sources, and nutritional options for the vegan communities.

Precision fermentation enables the cost-effective production of novel and previously impractical foods, including animal-free dairy and eggs, heme-based meat alternatives, bee-free honey, and bio-identical ingredients such as vanillin, omega-3 fatty acids, and vitamin B12 for sustainable nutrition [8,14,15]. It also supports vitamin and protein synthesis without antibiotics, hormones, or intensive livestock inputs, improving food safety and nutritional quality [16]. Although other reviews have addressed aspects of fermentation-based food innovation [17,18], they remain largely fragmented, technology-centric, or focused on single product classes, providing limited integration of environmental, industrial, and nutraceutical perspectives. This review critically examines these transformations, emphasizing environmental implications and the expanding role of precision fermentation in food and nutraceutical industries.

2. The past: Traditional fermentation

2.1. History, significance, and preservation techniques of traditional fermentation

Fermentation, one of the oldest food processing techniques, has been used by humans for thousands of years, with residues found in ancient pottery from 7000 BCE (Before Common Era) in China [19]. Initially discovered and utilized empirically, fermentation methods have evolved over time, producing a wide array of food and beverages such as bread, beer, wine, dairy, vinegar, soy-based products, yogurt, and pickles [17]. Fermentation was essential in improving food preservation when refrigeration and modern methods were unavailable, leading to longer shelf life. It also enhanced food flavors, bioactivity, and nutritional value [20]. Traditional fermentation gained popularity as the oldest and most widely accepted food processing method in human history, crucial for the survival and development of early civilizations centuries before the science behind fermentation was understood [5]. Bread-making, brewing, winemaking, and yogurt production are food processing traditions developed by ancient civilizations and refined over time [21]. Bread-making originated in ancient Egypt around 3000 BCE, when bakers discovered that leavening dough with wild yeast improved its flavor and digestibility [22]. Beer, one of the oldest alcoholic beverages, was produced in ancient Mesopotamia around 5000 BCE, using wild yeast to ferment grains like barley. Winemaking, on the other hand, began in Georgia around 6000 BCE, using yeasts from grape skins to convert grape sugars into alcohol [23]. Wine became an attractive drink in rituals, ceremonies, and daily life of ancient civilizations like the Egyptians, Greeks, and Romans [24]. Yogurt, discovered in Central Asia around 5000 BCE, was discovered in Central Asia due to naturally fermented milk stored in warm conditions. This led to thickened milk products with a tangy flavor and extended shelf life [25]. Cheese-making, dating back over 7000 years, may have started when milk was left in animal stomachs with natural enzymes and rennets, forming the first-ever cheese [26]. These methods proved efficient for preserving milk and enriching food nutrients in the prehistoric era.

The traditional fermentation methods vary with geographic locations, becoming a culturally significant phenomenon in many societies. This is because fermentation shapes societal culinary, dietary, and traditional inclinations through varied fermented products that often symbolize knowledge heritage passed down through generations and cultural identity integral to local cuisines [27]. The Ancient Greek culture recognizes wine as an important aspect of religious ritual done to honor Dionysus, the god of wine and celebrations [28]. Likewise, fermented foods such as kimchi, miso, and soy sauce are standard inherited traditional cuisines of many Asian societies [29]. The changing paradigm of fermentation technologies favors knowledge sharing, societal development, healthy dietary habits, and community resilience, preserving local food systems, and traditional knowledge [30]. In most traditional cultures, people brewed, baked, or pickled collectively as demonstrated today in some cultures in Italy. In parts of Africa, preparing some of the fermented foods like injera, a type of flatbread, or ogi, a type of fermented cereal is done through collaboration and knowledge sharing [31,32]. In the 19th century, Louis Pasteur established the microbial basis of fermentation, laying the foundation of modern microbiology and biotechnology. While transformative, this biologically centered view overlooked biochemical, ecological, health, and cultural dimensions that now define fermentation as a complex, multidisciplinary process [33].

2.2. Scientific advancements from traditional fermentation

Before Pasteur’s work, fermentation was already well-known and practiced, however, his insights led to a more comprehensive understanding of the role of microorganisms in fermentation that laid the foundation for the current innovative approaches to fermentation processes [34]. The popular "spontaneous generation" theory suggests that life forms could arise naturally from non-living matter, which explains the appearance of yeast and bacteria during fermentation [35]. Studying the fermentation of sugar into alcohol by yeast, demonstrated the critical role of microorganisms in metabolizing sugars into ethanol and carbon dioxide [36]. Moreover, critics of spontaneous generation, notably Pasteur, demonstrated that environmental microorganisms drive fermentation and spoilage, enabling the identification of specific microbes such as yeasts in alcoholic fermentation and lactic acid bacteria in sour milk, while laying the foundation of germ theory that transformed medicine and public health [37]. He introduced the concept of "pasteurization," a process of heating liquids like milk and wine to a specific temperature to kill harmful microorganisms without affecting the quality of the product. This became a critical method for improving food safety and extending shelf life, and it remains widely used today.

The early 20th century witnessed a significant understanding of the roles of yeasts and bacteria in fermentation due to increased studies of their nature and mechanisms of converting sugars into alcohol and carbon dioxide [38]. The knowledge offers opportunities for more precise control and optimization of fermentation processes to achieve product end-use benefits. One breakthrough in the annals of history was the development of pure yeast cultures, which offer brewers and bakers specific yeast strains to achieve desired products’ flavors and quality, improving their attractiveness, functionality, and marketability [39]. For example, Lactic acid bacteria (LAB) like L. casei, L. plantarum, and Lactobacillus brevis were identified as key to the fermentation of dairy products, fermented vegetables, and vinegar. Acetic acid bacteria, such as Acetobacter, convert ethanol into acetic acid, the primary component of vinegar [40]. While consistent advancement in fermentation research and innovation is developing the industrial food and beverage processes, the underlying principles of the technologies are also adopted for producing chemicals, such as acetone and butanol [41]. The isolation and use of pure cultures of yeast and bacteria lowers the risk of contamination, enhancing the safety and quality of fermented foods. The discoveries made in the early 20th century are the basis for the emerging field of biotechnology and the possibilities for genetic manipulations necessary for fermentation process precision and optimization.

2.3. Applications of fermentation in food

Fermentation became the cornerstone of food preservation and flavor development for thousands of years, producing a rich diversity of global fermented foods, beverages, and products (Table 1, Table 2). The benefits of fermentation and fermented produce are multifaceted, recognized, and exploited by cultures worldwide before human civilization. Fermentation biologically transforms basic ingredients, mostly carbohydrates, proteins, and fats, into complex, rich, and varied products of attractive flavors [42]. Food flavor is one of the crucial sensory properties that drives consumer acceptability [42]. It is influenced by volatile and non-volatile chemicals produced by microorganisms during processing. Proteins are metabolized into amino acids, which are transformed into aromatic compounds and lipids are hydrolyzed into fatty acids, which form cheesy flavors. Polysaccharides are decomposed into various flavor compounds [43]. The role of fermentation in improving food is shown in Fig. 1.

Table 1.

Typical traditionally fermented foods from different global regions.

Region	Traditional Food	Country	Health Benefits	Modern Food Developed	References
Africa	Injera	Ethiopia	Rich in probiotics, enhances gut health	Teff-based probiotics, gluten-free products	[44]
Africa	Ogi	Nigeria	Improves digestion, nutrient bioavailability	Fermented cereal-based probiotics	[45]
Africa	Acha (Tamba)	West Africa	High in fiber, aids in digestion	Gluten-free products, acha-based snacks	[46]
Africa	Kenkey	Ghana	Enhances gut health, rich in B vitamins	Fermented maize-based products	[47]
Europe	Sauerkraut	Germany	Supports immune function, rich in vitamins C & K	Probiotic supplements, functional foods	[48]
Europe	Kefir	Russia	Enhances gut health, may lower blood pressure	Kefir-based beverages, probiotic dairy	[49]
Asia	Kimchi	Korea	Anti-inflammatory, supports digestion	Kimchi-flavored snacks, sauces	[50]
Asia	Miso	Japan	Source of antioxidants, may reduce blood pressure	Misobased seasonings, soups	[51]
Asia	Tempeh	Indonesia	High in protein, rich in probiotics	Plant-based protein products	[52]
Asia	Dosa	India	Improves digestion, provides energy	Fermented batter-based products	[53]
North America	Sourdough Bread	USA, Canada	Aids digestion, lower glycemic index	Artisan breads, gluten-free sourdough	[54]
North America	Pickles	USA, Canada	Rich in probiotics, supports digestion	Probiotic pickles, fermented snacks	[55]
Oceania	Poi	Hawaii (USA)	Supports gut health, nutrient-rich	Poi-flavored snacks, probiotic products	[56]

Table 2.

Typical traditionally fermented beverages from different parts of the world.

Region	Traditional Beverage	Country	Health Benefits	Modern Beverage Developed	References
Africa	Fonio Beer (Pito)	West Africa (Ghana, Nigeria)	Provides energy, contains B vitamins	Craft beers, gluten-free beers	[57]
Africa	Kunu	Nigeria	Aids digestion, provides energy	Fermented millet-based drinks, non-alcoholic beverages	[58]
Africa	Burukutu	Nigeria, Ghana	Rich in probiotics, enhances gut health	Craft beers, probiotic-based beverages	[59]
Africa	Sekete	Nigeria Ghana	Contains B vitamins, provides energy	Fermented millet drinks, functional beverages	[60]
Asia	Apong	India		Fermente Rice drink, Functional beverage	[61]
Europe	Kvass	Eastern Europe	Aids digestion, contains B vitamins	Fermented bread beverages	[62]
South America	Chicha	Peru, Bolivia, Ecuador	Provides energy, may improve gut health	Fermented corn beverages	[63,64]
South America	Cauim	Brazil	Rich in vitamins, aids in digestion	Fermented cassava beverages	[65]

Fig. 1.

Role of fermentation in improving food quality.

Fermentation enhances the nutrient quality of foods and modulates complex macronutrients and micronutrients to ensure their bioavailability. It also decreases anti-nutritional factors like polyphenols in grains, tannins in fruits, oxalates in vegetables, cyanogenic glycosides in cassava, and phytic acid in legumes [66]. Phytates, tannins and oxalates in foods interfere with proteins and bind nutrients (iron, zinc, calcium), hindering their bioavailability and digestion [67,68]. Studies have shown that fermentation enhances the bioavailability of plant proteins by inactivating protein inhibitors in fermented foods [[69], [70], [71]]. Fermentation have improved bioavailability of nutrients such as calcium, iron, zinc in fonio flour compared to the unfermented flour [72]. Plant proteins have lower digestibility when compared to animal proteins, leading to gastrointestinal upset and food allergies. Improving protein digestibility by facilitating proteases can reduce undigested proteins in feces, prevent food allergies caused by poor absorption in the gut, and promote functionality [73,74]. Probiotic dairy products such as yogurt and kefir contain B vitamins that are synthesized during fermentation by lactic acid bacteria. Advancements in fermentation studies found that fermentation causes the synthesis of bioactive compounds with antioxidant, anti-inflammatory, anti-obesity, antidiabetic, and immunomodulatory values [75]. Misoand kimchi have isoflavones and other active compounds are crucial in preventing chronic diseases [76].

Fermentation also intricately deactivates toxins and toxic elements naturally inherent in foods, ensuring their safe for human consumption. The fermentation of cassava into products like gari, ogi or cauim lowers the cyanogenic glycosides content capable of lethal intoxication if not properly processed [77]. Probiotics in fermented foods are enhanced by the process, introducing live microorganisms into the guts and intestines to mediate digestion, mental health through the gut-brain axis, and inflammations [78,79]. The glycemic index of foods is lowered by fermentation, producing functional foods like sourdough important for individuals managing blood sugar levels. Sourdough bread has a lower glycemic index than regular bread, leading to slower digestion and a more gradual rise in blood glucose levels [80]. Additionally, fermentation can reduce the caloric content of foods by converting sugars into acids, alcohol, and gases, which are either consumed by microbes or evaporated during the process [81,46].

Starch, the primary carbohydrate in many developing countries' cereals, legumes, and plant-based diets, offers the greatest number of calories [82]. Enzymes that hydrolyze starch, such as α-amylase and maltase, are activated during fermentation and convert starch into maltodextrins and simple sugars, respectively [83]. Research has demonstrated increased glucose during the initial stages of fermentation due to enhanced starch-hydrolyzing activity of maltase and α-amylase [84,83]. This results in total carbohydrate reduction after 24 h of fermentation, affirming glucose release in the system due to enhanced microbial activities [83]. When both sugar molecules are present in the pearl millet fermentation system, fructose content stays constant, hypothetically supporting glucose as the preferred energy source for many microorganisms [85].

Fermentation may affect the phytochemicals of foods positively or negatively, changing their configuration, composition, and concentration to functional metabolites or more absorbable bioactive forms [86]. Therefore, fermentation is a veritable tool utilized since the beginning of the century to enhance foods’ phytochemical compositions, and functional benefits to humans [87,88]. Depending on the length of a fermentation process, a considerable amount of carotenoids may be lost when fermenting corn high-carotenoid biofortified corn [89,90]. 60 %−100 % of provitamin A carotenoids may be retained during the 24- and 72-hour fermentation of biofortified corn. Nevertheless, retention dramatically dropped to between 27 % and 48 %, depending on the maize genotype, after 120 hr of fermentation [90]. Fermentation does not only affect nutritional component of fermented foods, Obayomi et al., also reported an increase in techno functional and physical properties of fermented fonio flour [72,91].

3. The transition

3.1. Transition from traditional to precision fermentation

Precision fermentation remains an evolving technique with deep historical roots and diverse prospective applications. It uses genetically modified microorganisms like yeast, bacteria, or molds to produce special molecules like proteins, fats, and bioactive compounds [7]. This technology precipitated from an improved understanding of ancient fermentation and accompanying scientific advancements has recently attracted interest [92,11]. This is because of its potential to provide humane and environmentally friendly solutions compared with conventional animal products used in foodstuffs, medicines, and pharmaceuticals [11]. The attractive attribute of precision fermentation lies in its scalability, effective resource consumption, and opportunities for producing a vast range of molecules [93]. However, the commercialization of precision fermentation is challenged by public perception, the shift from using naturally existing microbes, and regulatory framework work due to uncertainties associated with genetically modified microbial fermenters applied in the system [92]. This may be why traditional fermentation dominates many cultures in developing countries even though precision fermentation uses genetic engineering to direct microorganisms to efficiently produce purifiable target compounds that were previously not synthesized by them in substantial amounts [6]. Precision fermentation uses selected genes from microbial, plant, or animal sources to produce target compounds in engineered microbes grown in controlled bioreactors, enabling high-purity products through advanced purification and expanding their commercial use in food, cosmetics, and pharmaceuticals [12,17].

3.2. The development of synthetic biology

The transformational changes favoring significant growth in synthetic biology were charted in the 1990s and 2000s, following early groundwork laid in the 1970s and 1980s by systematic advances in genetic engineering studies [94]. The studies marked the advancement in genetic modification, metabolic engineering, and synthetic biology to alter biological systems for variegated applications like precision fermentation. Additionally, these advances lead to efficient techniques in recombinant DNA and precise insertion into host organisms [95]. Genetic tools like restriction enzymes and ligases were advanced with the development of plasmid vectors for gene manipulation. The 90 s marked the period when ‘transgenic’ organisms were developed and widely utilized. Transgenic organisms are those organisms in which the DNA of another species has been introduced into its body [96]. This was not only a basic microorganism but also plants and animals [97]. The application of foreign genes in these organisms was the key that opened the way to the growth and development of biotechnology, agriculture, and pharmaceuticals.

The CRISPR-Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats) system as a third-generation technology which offered an effective and accurate method of slicing genomes [98]. As demonstrated in previous gene editing methods, CRISPR-Cas9 allowed editing genes with great efficiency and turnaround time superior to that associated with past methods zinc finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs). These synthetic biology tools, which share foundational principles with recombinant DNA technologies may be replicated in fermentation to engineer microorganisms. Although these methods are efficient in genetic modifications with high-level specificities, their procedures are more complicated except for CRISPR, leading possibly to lower success rates [99]. Recent studies have looked at the modulation of the microbiome using CRISPR technology to control and enhance microbiota in fermentation systems and improve fermented foods and beverages' quality and shelf stability. They also allow the selective elimination of all undesirable microbial associates that are known to cause spoilage and compete with the natural fermentation inoculums [100]. Escherichia coli was the model microbe and CRISPR/Cas9 became the model tool for specific targeting of individual microbial strains within microbial consortia to accomplish particular sequences [101].

Metabolic engineering emerged as a distinct discipline in the 1990s and focused on improving cellular processes through modifying metabolic pathways. The overwhelming need to optimize the production quality and functionality of desired pharmaceuticals, biofuels, and food ingredients has facilitated microorganisms' metabolic engineering networks under various environmental constraints [102]. Following this, scientists gained systematic control of biological systems, optimizing genetic and regulatory processes involved in metabolic and biochemical pathways. Thus, the identified active enzymes are being targeted and controlled in metabolic pathways to increase the production of desirable products. This confirms the significance of metabolic engineering to precision fermentation, which relies mostly on genetically engineered microorganisms to produce specific high-valued compounds [10]. For instance, the biosynthesis of lysine, a nutritionally essential amino acid, was enhanced in Corynebacterium glutamicum through targeted manipulation of its metabolic route for high-quality lysine output [103]. Hence, many engineered strains of microorganisms could now sustainably and efficiently metabolize different feedstocks, reducing production costs and high-valued outputs [104]. By the early 2000s, synthetic biology began complementing metabolic engineering for holistic microbial metabolic network effect in precision fermentation, merging distinct scientific fields and principles from biology, engineering, and computer science [105]. Unlike traditional genetic engineering technologies, which only modify existing organisms, synthetic biology redesigns and reconstructs new biological parts, devices, and systems’ functions from the ground up (Fig. 2). While traditional fermentation relies on natural and historical processes focused on wild or domesticated microorganisms to transform food and produce beverages, genetic Engineering uses direct alteration of genetic material to achieve specific traits, often used for producing pharmaceuticals or GMOs.

Fig. 2.

Schematic representation of major transitional difference from traditional fermentation to precision fermentation.

Synthetic biology introduced the concept of modularity in biological systems, allowing scientists to design, and assemble standardized genetic parts (BioBricks) to create new functions in living cells and enhance outcome predictability [106]. The technology also encourages using cell-free systems, replicating biological reactions in vitro, and outside living cells. This system attribute facilitates testing, optimization, and control flexibility of synthetic circuits without the complexities of cellular regulation [107,108]. The food industry has embraced this biotechnological approach to develop enzymes, vitamins, and other food additives through precision fermentation [109]. For example, Mohanty et al. used genetically engineered microbes to produce chymosin, an enzyme traditionally sourced from calf stomachs for cheese production, reducing the need for animal-derived ingredients [110]. Therefore, precision fermentation combines genetic engineering and fermentation to produce specific ingredients, mainly for modern food, pharma, and industrial applications.

4. Precision fermentation in food production

4.1. Proteins and enzymes

Rapidly expanding global protein demands and markets have expanded precision fermentation applications, leading to a range of uniquely designed functional proteins [7]. Precision fermentation enables the biosynthesis of a wide range of food ingredients, including volatile flavor compounds, hydrophobic pigments, and hydrophilic sweeteners, through coordinated upstream metabolic engineering and downstream separation and purification strategies (Fig. 3). Jin et al. and Tim et al. used precision fermentation to produce plant-based egg and dairy proteins (casein and whey) characterized by essential amino acids (AAs) crucial in cheese, yogurt, and milk products [111]. Alpha, beta, and kappa caseins are crucial for animal-free cheese production due to their emulsification and gelation properties. Start-ups like Formo, New Culture, and Standing Ovation are targeting caseins while whey proteins like beta-lactoglobulin with excellent solubility and foaming properties, are being targeted by companies like ImaginDairy, ReMilk, and Perfect Day. Because of its high value and limited quantity in bovine milk, lactoferrin, an iron-binding whey glycoprotein with immune-protective and antibacterial properties, is a possible target for precision fermentation. Egg white proteins, or EWPs, are used in ice cream, baked goods, and dietary supplements, among other culinary products [11]. Researchers at various biotech industries like Valtion Teknillinen Tutkimuskeskus (VTT) technical research Centre of Finland and Onego-Bio successfully produce animal-free protein foods like ovalbumin in Trichoderma reesei, showing excellent product functionality [11]. Precision fermentation plays a vital role in creating meat substitutes, producing proteins that mimic the sensory properties of the meat. For instance, myoglobin, hemoglobin, and leghemoglobin mimic the colour and taste of normal meat [112]. The EVERY Company has produced precision fermentation derived ovomucoid (Generally Recognized as Safe Notice (GRN 967) and ovalbumin (GRN 1107) using yeast (Komagataella phaffii), and the GRN 967 has particularly high solubility and therefore appropriate for use in beverages [113]. Also, Novonesis has developed a precision fermentation-based lysozyme for food processing also [114]. Impossible Foods produces leghemoglobin, while myoglobin is commercialized by Motif Foodworks and Paleo [115]. Precision fermentation is also revolutionizing the production of sweet proteins, such as brazzein, monellin, and thaumatin, which are significantly sweeter than sugar [116]. These proteins offer a solution for sugar reduction while maintaining taste. Companies like Oobli and Mycotechnology are commercializing precision fermentation derived sweet proteins to meet the growing demand for healthier, sustainable food options [11]. Collagen, commonly derived from animal connective tissue, is essential in various food products due to its gelation properties. However, challenges related to safety and sustainability are driving precision fermentation applications. Geltor already offers precision fermentation collagen for nutraceuticals and plans to scale its use in dietary applications [112].

Fig. 3.

Precision fermentation platform for the production of food ingredients. (a) Representative classes of fermentation-derived food compounds, including volatile flavor molecules (e.g., limonene, linalool, vanillin), hydrophobic pigments and heme proteins (e.g., β-carotene, astaxanthin, lycopene, heme), and hydrophilic sweeteners and colorants (e.g., rubusoside, rebaudioside, betanin). (b) Upstream bioprocess strategies used to enhance product biosynthesis, including host strain selection (e.g., Escherichia coli, Saccharomyces cerevisiae, Corynebacterium glutamicum, Bacillus subtilis), metabolic pathway balancing, exporter engineering, adaptive laboratory evolution, feedback-resistance engineering, by-product elimination, co-culture systems, and lipid engineering for intracellular product storage. (c) Downstream processing and recovery routes, including cell separation, disruption, extraction, purification, and formulation, employing technologies such as centrifugation, filtration, liquid-liquid extraction, supercritical fluid extraction, chromatography, distillation, spray-drying, and encapsulation to obtain food-grade products. Reproduced with permission from [18], Copyright 2025, Current Opinion in Food Science.

4.2. Flavor and aroma compounds

Precision fermentation enables the production of key flavor, aroma, and functional compounds that give plant-based meats and dairy alternatives authentic sensory qualities essential for consumer acceptance [6]. Fermented foods are made with fermenting microorganisms metabolically engineered to modify their flavor profiles. Strains of Sacharomyces cerevisiae remain industrially relevant because of their capacity to generate high titer of the specific flavouring compounds that are relatively cheaper and safer than the chemical analogs. Flavouring compounds in this category include aliphatic aldehydes like vanillin, methyl anthranilate, cinnamaldehyde, and diacetyl. Soy leghemoglobin, which is produced by Komagataella phaffii overexpression contains heme which imparts rich meat flavour [[117], [118], [119], [120]]. Saccharomyces cerevisiae ML01 with a malate transporter Schizosaccharomyces pombe (SpMAE) and a pre-fermentation malic enzyme from Oenococcus oeni mleA were used for malolactic and ethanolic fermentation of wine with softer taste [121]. Also, yeast with lactate dehydrogenase produces sourness in beer drinks, and hoppy flavour yeasts overexpressed linanool and geraniol synthases imparted hop taste to beer even when no hops were used [122]. Studies highlighted salient concerns related to the safety risk of products, quality control consistency, ethical considerations, and consumer perceptions in the application of precision fermentation for food production [10]. Precision fermentation can introduce allergenic or toxic proteins food products, and host cells or yield low titers that may be alleviated by cellular and bioprocess engineering [92]. The initial investment, operational cost, and expertise in precision fermentation technologies may significantly impact sustainable production, costs, and access to flavor compounds in food processing. However, fermented beverages may be unattractive to consumers due to the use of transgenic microorganisms [7].

4.3. Functional foods and nutraceuticals

Precision fermentation allows for the tailored production of functional foods and nutraceuticals with enhanced stability and efficacy. Functional foods are foods that provide health benefits beyond their basic nutritional value, such as vitamins, minerals, or calories [123]. They often contain bioactive compounds like antioxidants, peptides, prebiotics and probiotics that can prevent or manage diseases and improve overall health [124]. Nutraceuticals are products derived from food sources that offer medical or health benefits, including the prevention and treatment of diseases. Examples include omega-3 fatty acids, collagen peptides, and bioactive proteins [125]. Probiotics are live microorganisms that, when consumed in adequate amounts, confer health benefits to the host, primarily by improving or restoring gut flora [126]. Probiotics improve or restore gut flora, promoting effective digestion and nutrient absorption. Consuming probiotics in adequate amounts can alleviate symptoms of irritable bowel syndrome, inflammatory bowel disease, and diarrhea by maintaining a balanced gut microbiome [127]. Common strains such as Lactobacillus and Bifidobacterium support gut health by promoting the growth of beneficial bacteria and inhibiting harmful pathogens [123]. Precision fermentation enhances probiotic production by improving strain survival, stability, and functionality. For example, Lactococcus lactis and Lactobacillus rhamnosus exhibit increased acidifying capacity, acid tolerance, and resistance to nisin Z through continuous fermentation [128,129]. Co-cultures of Bifidobacterium longum and Lactococcus lactis show improved survival under oxidative stress, freeze-drying, and gastrointestinal conditions [130]. Additionally, precision fermentation alters exopolysaccharide production in Lactobacillus rhamnosus, boosting aggregation and gut colonization [131]. These improvements ensure probiotics are more stable and effective for gut health interventions. Prebiotics are non-digestible food components, typically fibers, that selectively promote the growth and activity of beneficial gut bacteria, thereby improving host health [132]. Inulin, a naturally occurring prebiotic fiber promotes the growth of beneficial bacteria like Bifidobacterium and Lactobacillus in the gut [123]. Precision fermentation provides opportunities for the customized production of prebiotics with optimized structures for targeted health benefits. Omega-3 fatty acids, a popular nutraceutical, can reduce cardiovascular disease risk and can be synthesized using precision fermentation and engineered microalgae for vegans and other conditions [124]. Companies like Geltor produce precision-fermented collagen peptides as nutraceuticals for improved skin and joint health [12]. Bioactive proteins and peptides, including casein and whey peptides, offer health benefits like immune support, anti-inflammatory effects, and improved athletic performance, making them valuable in sports nutrition and therapeutic food products [125]. Companies like Motif FoodWorks have used precision fermentation to produce heme proteins like myoglobin to enhance the taste and nutritional profile of plant-based meats while also offering bioactive benefits [11].

5. Precision fermentation in sustainable markets and environmental resilience

5.1. Precision fermentation in business and market

In 2021, $1.69 billion was invested in fermentation companies and is projected to grow at a compound annual growth rate of 46 % between 2023 and 2032, or roughly USD (United States dollars) 67.9 billion. Precision fermentation costs have witnessed an exponential decrease since its first molecules were produced, with proteins expected to be $10/kg by 2023–2025 [133]. During the short period of 2013 to 2022, this industry saw the emergence of numerous new businesses. These businesses have raised an astounding USD 1.946 billion [134]. Although the precision fermentation sector is still in its infancy, major food conglomerates such as Nestlé (Vevey, Switzerland), Unilever (London, Great Britain), AB InBev (New York, NY, USA), and General Mills (Minneapolis, MN, USA) have expressed interest in adopting it [134]. To unlock the market for food products, the cost of production for biomass fermentation needs to be reduced through corresponding reductions in cultivation and harvesting costs. Reducing nutrient costs requires using inexpensive resources as alternatives, decreasing labor costs through automation and machine learning, and lowering power consumption across the production steps [10]. Precision fermentation is now driven by pioneering companies delivering scalable, animal-free ingredients for sustainable food systems. Perfect Day produces dairy proteins such as whey and casein for products like ice cream, Impossible Foods uses soy leghemoglobin to recreate meat flavor and texture, Geltor supplies animal-free collagen and gelatin, and Motif FoodWorks develops functional proteins to improve the taste, texture, and nutrition of plant-based foods [10].

5.2. Precision fermentation’s impact on the environment

Many works have demonstrated that food production and processing contribute to addressing environmental impacts [135,136]. This is particularly obvious in food production industries involving animal agriculture and products. The rise in regional and global coalitions is being formed to conserve the planet and make it more resilient to climate change and pollution effects [137,138]. The 28th Conference of the Parties (COP28) to the United Nations Framework Convention on Climate Change (UNFCCC), held in the United Arab Emirates (UAE), focus on sustainable agriculture, resilient food systems, and climate action to foster the earth's invigoration. The communique signed by >150 nations that attended the United Nations Convention on Climate Change referred to as the Conference of the Parties (COP) emphasized the need to transform food systems on the global climate agenda (COP28 UAE) for the first time in its 28 editions [139]. Compared to conventional farming, precision fermentation can serve as a partial solution to crucial global problems relating to the depletion of resources, emission of greenhouse gases, and loss of biodiversity.

5.3. Resource efficiency

Conventional farming is capital-demanding, requiring land, water, and feed to produce animal-based foods. Similarly, according to the environmental impact analysis supported by the Food and Agriculture Organization (FAO), about 80 % of the world’s forests are cleared for agriculture [140]. One such alarming instance is the Brazilian Amazon, where deforestation in 2019 and 2020 increased to 11 million hectares yearly due to weak enforcement of the laws that ban deforestation. Increased cattle ranching and soybean farming activities in the area have turned the Amazon from one of the best global carbon sinks to a carbon emitter, adding to existing worries over climate change impacts [141,142]. In contrast, precision fermentation uses less land than traditional farming techniques, making dairy protein production through fermentation an efficient way to get rid of pasture or crops for animal feeds. This land use change assists in the conservation of ecosystems and eventually controls deforestation, allowing better use of available resources.

Precision fermentation are now used in manufacturing proteins and other food ingredients in controlled environments to minimize significantly the alteration of natural ecosystems [143]. This can favour species diversity and resilient ecosystems crucial for sustainable environmental balance. The efficient application of precision fermentation is far greater than livestock agriculture in water resource management [144,145]. For instance, precision fermentation produce animal-free dairy proteins, such as whey, through fermentation uses 60–90 % less land and water than conventional dairy farming, which require a humongous water supply to hydrate the animals, irrigate the feed crops for the animals, and wash milking equipment [146,6,147]. Furthermore, conventional farming methods harm the environment by seeping contaminants like fertilizers, pesticides, and animal excreta through runoffs into underground water bodies [148]. Therefore, precision fermentation takes place in highly controlled closed systems, circumventing any direct impact on underground water quality and minimizing pressure on freshwater supplies. Animal agriculture uses large tracts of land to optimize animal yields such as meat, milk, and eggs. Precision fermentation eliminates requirements like animal feed, land, and labor, saving energy and resources that could be diverted to the production of food for the growing human population. Precision fermentation systems can be powered by renewable energy sources, reducing environmental footprint [149]. As technology advances, there is a prospect for integrating solar, wind, or bioenergy to power fermentation facilities, enhancing the sustainability of the entire production process.

5.4. Greenhouse gas emissions reduction

Agriculture is a major contributor to greenhouse gas (GHG) emissions, particularly methane from livestock and carbon dioxide from land-use changes. Analysis of environmental implications, supported by the FAO, reveals that agriculture is the main agent of global deforestation, being responsible for around 80 % of it [140]. Livestock, particularly ruminants like cows and sheep, produce significant amounts of methane, a potent greenhouse gas, through enteric fermentation estimated at between 11 % and 20 % serves as the main area of focus [[150], [151], [152]].. However, the effects extend beyond greenhouse gas emissions and include significant modifications to the Earth system. Surprisingly, just 18 % of the calories and 37 % of the proteins consumed worldwide come from the production of meat, eggs, dairy products, and aquaculture, which occupy 83 % of the world's agricultural land [150]. Replacing traditional animal agriculture with precision fermentation reduces methane emissions significantly, contributing to climate change mitigation. Studies have shown that precision fermentation produces products like proteins and other compounds that have lower greenhouse gas footprints than conventional livestock farming [12,153]. These reductions make precision fermentation one of the power tools in the fight against the food industry’s carbon footprint. Hence, precision fermentation is less resource-intensive than traditional farming practices in carbon impact. This suggests that the process can be designed to be carbon-free, particularly if powered through renewable energy or energy smart. However, some firms have begun to look at the possibilities of precision fermentation in accomplishing carbon-free or neutral, and carbon-negative environment [154]. This could involve using the captured carbon dioxide as a substrate for fermentation processes such that a waste product to the system is reused to produce new products and reduce atmospheric CO₂ concentrations.

5.4.1. Biodiversity conservation

Most conventional farming practices contribute to environmental degradation such as habitat loss, monoculture planting, and pesticide application [155]. However, animal production has exceeded freshwater consumption, constraining in a few countries and posing threats to bio-diversity [156,157]. Thus, livestock farming exerts considerable pressure on water resources, affirming the large amounts of water required for agriculture, amounting to about 70 % of global total freshwater extraction [158]. Precision fermentation allows the utilization of less agricultural land and the application of fewer chemicals, alleviating land use pressures and transforming forests, wetlands, or other natural landscapes into farmland. This facilitates biodiversity and sustainable ecological systems, enhancing conservation practices and ecosystems’ service benefit to humanity. Conventional agricultural practices are linked to the pollution of watercourses by excessive use of fertilizers and pesticides, posing threats to marine life and biological diversity [159]. On the contrary, precision fermentation contributes to minimizing the use of chemicals (pesticides, fertilizers, antibiotics, etc.) thus mitigating the degradation of the soil, water, and other life forms in the environment.

6. Precision fermentation and the health sector

Precision fermentation is an emerging technology used to produce proteins, enzymes, and other biomolecules. It is specially designed to genetically modify microbes to synthesize products valuable in the food industry with recent incursions into healthcare. Innovations in synthetic biology, genetic engineering, and metabolic engineering have enhanced the benefits of precision fermentation in the healthcare sector including in the production of pharmaceuticals, therapeutics, nutraceuticals, and personalized medicine [160,161]. Consequently, biopharmaceutical (BPH) production remains one of the most important areas harnessing precision fermentation in the health sector. In most cases, complex proteins like insulin or monoclonal antibodies have been synthesized from a mammalian cell culture system, which is a more expensive and slower production route [162]. The versatile nature of precision fermentation, particularly its compatibility with a range of beneficial microorganisms gave it a superior edge in biopharmaceuticals The first rDNA-based insulin, Humulin® R (rapid) and N (NPH, intermediate-acting), went on commercialization in 1982 [163]. The recombinant and genetically engineered bacteria such as E. coli are produced to make human insulin which is crucial to treat diabetes. This method, has enhanced access and cheap supplies of insulin, improving the health of millions of people around the globe [164]. Precision fermentation is also applied to the manufacture of monoclonal antibodies, which are essential in the treatment of various diseases such as cancer, autoimmune diseases, and viral diseases. Therefore, growing microorganisms to secrete these antibodies with this technology becomes cheaper and yields larger volume for the benefit of the patients [165]. It is also used in the preparation of vaccines and therapeutic proteins. For instance, it may be applied to produce antigens in vaccines important for averting infections [166]. The fact that these antigens can be produced precisely and in large volumes gives precision fermentation a practical use, especially in resolving health crises like disease outbreaks.

7. Role of precision fermentation in sustaining circular economy and food waste valorization

Precision fermentation is amenable to circular economic production since it relies on renewable resources and generates insignificant waste at every stage. As opposed to more conventional forms of food production that require extensive resources and produce several forms of waste. Precision fermentation utilizes the principles of microbial fermentation to produce highly efficient and target-food ingredients with negligible negative effects on the environment [167]. Precision fermentation can turn waste, particularly food waste and agricultural residues into value-adding resources (Fig. 4). The use of byproducts such as fruit peels, spent grains, or vegetable scraps as feedstock for microbial cultures in precision fermentation can lead to functional ingredients like proteins, enzymes, or bio-based chemicals. Precision fermentation can utilize a variety of sustainable feedstocks, including agricultural waste, food waste, and even carbon dioxide [168]. As a typical feedstock, lignocellulosic materials frequently require conversion into fermentable sugars for precise fermentation and biomass production. Sidestreams from food and agricultural activities that already include fermentable sugars provide alternate feedstocks. Studies made use of sidestreams like fruit pomaces (apple, pomegranate, and aronia), leaf spinach, and beet molasses [169], potato protein liquor [170], brewer's spent grains, malt spent rootlets, cheese whey, molasses, orange, and potato pulps ([171], and rice bran [172].

Fig. 4.

Role of Precision fermentation in circular economy and valorization.

The valorization process inherent in precision fermentation not only addresses food waste but also contributes to reducing the environmental footprint of food production by diverting organic waste from landfills, where it would otherwise contribute to greenhouse gas emissions. Precision fermentation can be integrated with renewable energy systems, such as biogas production to enhance sustainability. For example, waste from fermentation processes can be used to generate biogas, which can later be used to power the fermentation facility, creating a closed-loop system [173]. Mirfakhar reported that through fermentation of starchy and lignocellulosic wastes, Saccharomyces cerevisiae and Clostridium acetobutyricum generate bioethanol and biobutanol [174]. Tsai et al., also reported the production of Biobutanol from lignocellulosic biomass through the use of immobilized Clostridium acetobutylicum [175]. However, enzymatic pre-treatment is necessary to break down polymer chains into glucose monomers [176]. Biofuels can be produced from various substrates, such as vegetable and animal lipids, pyrolysis, and AD of biodegradable substrates [34]. Sugarcane industry byproducts can be used for bioethanol synthesis, AD, microbial fermentation, and microalgae culture [177]. Genetically modified bacteria can use lactic acid fermentation to create bioplastic products. Polylactate is used for biodegradable items with limited shelf-life, such as films and packaging bags. Polyhydroxyalkanoates, such as poly [(R)-3-hydroxybutyrate], are used in various settings, including packaging [178,179]. These novel materials are made from agricultural and food waste and offer improved transparency, biocompatibility, and processability [180,181]. Precision fermentation can complement traditional agriculture by providing sustainable alternatives for certain ingredients, while traditional farming can focus on producing crops and products that are difficult to replicate through fermentation. This collaboration can lead to a more balanced and sustainable food system.

8. The future: Potential and challenges of precision fermentation

Precision fermentation is expected to disrupt the food industry because of the development of environmentally friendly, nutrient-rich, and functional foods. Although it facilitates the creation of new proteins with precise amino acid composition and that imitate animal products, flavors, and ingredients, it raises safety concerns about allergenic proteins, toxins, human perceptions of genetically modified food, and commercialization. It shall equally be instrumental in blended foods made from plant and lab-grown meats, and cultured meat with proteins derived from fermentation, which are better by way of nutrition and flavor. High-valued functional proteins with certain targeted health benefits could be developed to meet the needs for more functional, individualized nutrition. Recent developments in artificial intelligence and machine learning may complement fermentation strategies, enhancing their efficacy and lowering the overall cost to humanity and the environment. The potential application of artificial intelligence in fermentation technologies and their applications in various industries may accelerate the development of new products, especially using predictive models for optimization, reducing experimentation turnaround time and operational costs. Some newer techniques in synthetic biology include CRISPR and gene editing, which make it possible to have a specific set of attributes in the fermentation microorganisms. Nevertheless, precision fermentation must obey regulatory systems and guidelines, and embrace standardization disclosure in labels worldwide to encourage consumers’ acceptance, affordability, and market share. Their integration into the technology supply chain, ethical cultures, environmental actions, and sustainable healthcare services create new innovative frontiers. In the collective actions to reduce the negative impact of company discharge into the environment, intensifying efforts at allocating resources for renewable power, water, and sustainable procurement are crucial considerations. Precision fermentation is becoming recognized as an innovative approach in the food industry, slowly replacing traditional concepts and technologies in resolving contemporary agricultural, medical, and food challenges. Complementing cell farming with agriculture offers the best opportunity to resolve global hunger, replicating soil cultivation in bioreactors for more efficient, sustainable, and robust food production systems. Precision fermentation is presently characterized as potentially veritable and fraught with uncertainties regarding its future, suggesting the need for greater research investments, collaborations, and partnerships to foster better awareness.

9. Conclusion

Precision fermentation is a modern and enhanced version of traditional fermentation that has become a part of cutting-edge food technology. It provides a versatile approach to develop healthy, balanced, and differential food products of finer flavours and longer shelf life. Over the years, precision fermentation has emerged and slowly evolved, recording massive achievements in microbial roles, genetic engineering, and synthetic biology. Perfect Day and Impossible Foods are some of the few frontline companies in the corporate world offering products tailored to improve sustainability and food security. Even though the foundational building blocks of precision fermentation offer promises of fostering variable novelties in food and food ingredients, climate change mitigation, resource conservations, and food security, its prospects are confounded concerns. These concerns may be regulatory, political, economic, cultural, or ethical. Hence, to realize the full potential and spread of precision fermentation consistent efforts in an intersectoral coalition, and continuous investment in research must be considered. Even more important are ethical standards shaping the approach to businesses relying on precision fermentation technologies, and cultural belief systems in revolutionizing the production of food products and their consumption. Integrating emerging technologies like molecular, genetic, metabolic, and machine learning technologies into the 10,000-year-old fermentation could offer science limitless possibilities to produce previously impossible plant-free, animal-free, and transformed food products. These advancements may positively contribute to waste management efforts and lower greenhouse gas emissions, carbon footprint, and biodiversity loss, leading to healthier, more benign environmentally, and sustainably stable food systems worldwide.

CRediT authorship contribution statement

Oluwatobi Victoria Obayomi: Writing – review & editing, Writing – original draft, Visualization, Validation, Conceptualization. Adekunbi Adetola Malomo: Writing – review & editing, Validation, Conceptualization. Abiola Folakemi Olaniran: Writing – review & editing, Validation, Supervision. Omorefosa Osarenkhoe Osemwegie: Writing – review & editing, Validation, Supervision. Ayoyinka Olufunke Olojede: Writing – review & editing, Validation, Resources. Olanrewaju Eunice Beyioku: Writing – review & editing, Validation. Oluyomi Stephen Adeyemi: Writing – review & editing, Validation, Conceptualization, Supervision.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Data availability

No data was used for the research described in the article.