Intersecting precision fermentation for global cell-based food production innovation: Challenges and opportunities

Cell-based food production relies on cultivating animals, plants, or microorganisms in a controlled environment to produce food products, ingredients, or additives; therefore, represents a new type of food resource and biotechnological production system (Guan et al., 2025; Rischer et al., 2020). It has many advantages, such as reducing environmental impact, animal welfare ethical issues, and the risks of disease outbreaks and antibiotic resistance encountered with traditional husbandry, and responding to global food security, resource shortages, and ecosystem health challenges (Guan et al., 2025; Ye et al., 2022).

Precision fermentation, an emerging hotspot in cellular agriculture, is increasingly recognized as a pivotal process intersecting with cell-based food production, although it does not have an internationally agreed-upon definition (https://www.fao.org/food-safety/scientific-advice/crosscutting-and-emerging-issues/cell-based-food/en/). Generally, it strategically utilizes engineered microorganisms as “microbial cell factories” to synthesize specific ingredients (Eastham and Leman, 2024). Recent scientific discourse highlights the potential of these chassis cells to function as miniature production facilities (Augustin et al., 2024; Eastham and Leman, 2024; Hilgendorf et al., 2024).  This innovative paradigm, enables the expression of heterologous biosynthetic pathways in chassis cells, representing a transformative approach to food ingredient manufacturing. These targeted ingredients often attain higher purity levels than conventional raw materials and can be incorporated at desired concentrations, thus significantly enhancing diverse food products' sensory properties and functional attributes, including meat substitutes, dairy and sugar alternatives, beverages, etc. Innovative engineering techniques that enhance the fermentation-enabled food production are paramount. Noticeably, the iterative Design-Build-Test-Learn (DBTL) cycle in synthetic biology and metabolic engineering is rapidly evolving, facilitated by advancements in automated methodologies (Chai et al., 2022; Cho et al., 2025). These innovations expedite the refinement of engineered strains to achieve optimal phenotypes effectively through precise selection (Cho et al., 2025; Seo and Jin, 2022). This approach reduces unwanted metabolic competition and limits byproduct formation, making production more efficient and sustainable. Enhancing catalytic efficiency through engineered synthetic pathways further boosts microbial productivity, allowing a scalable and reliable supply of essential food ingredients (Eastham and Leman, 2024). Leveraging the DBTL framework, “microbial cell factories” can facilitate the scalable and sustainable production of crucial compounds such as proteins, amino acids, carbohydrates, fatty acids, and vitamins (Cho et al., 2025; Dupuis et al., 2023; Eastham and Leman, 2024; Lv et al., 2021; Vinestock et al., 2024), thereby addressing the growing demand for high-quality, functional food ingredients (Hilgendorf et al., 2024). Other manufacturing techniques, such as 3D bioprinting, may play a critical role, for example, in the microbial-derived scaffolds used in cell-cultured meat products (Gnaim et al., 2025; Guan et al., 2024, Guan et al., 2025). Moreover, the integration of intelligent catering solutions powered by big data analytics and interactive food design will further refine food manufacturing processes (J. Gao et al., 2025b, Gao et al., 2025a).

The paradigm shift in consumer expectations directly intersects with cell-based production and precision fermentation's capacity to address unmet needs in food customization (Dupuis et al., 2023; Lv et al., 2021; Teng et al., 2021). Modern consumers seek food products that are visually appealing and nutritionally enriching, with a strong emphasis on health benefits. Importantly, there is a notable trend toward personalized nutrition, where consumers desire food tailored to their unique dietary needs and preferences, while precision fermentation within cell-based production enables targeted synthesis of these structurally complex, nutritionally tailored food ingredients (Cho et al., 2025; Guan et al., 2025; Hilgendorf et al., 2024). Precision fermentation represents a cutting-edge advancement, with the potential to revolutionize, for example, sustainable cell-based protein production within the circular bioeconomy (Akharume et al., 2021; Cho et al., 2025; Dupuis et al., 2023; Eastham and Leman, 2024; Hilgendorf et al., 2024). As global protein demands continue to rise, it is essential to diversify our protein sources beyond traditional options such as meat, dairy, eggs, seafood, and plant-based products (Akharume et al., 2021; Dupuis et al., 2023; Eastham and Leman, 2024). Emerging alternatives, including microbial cultures derived from yeast, fungi, algae, and insects, offer complementary protein sources capable of bridging the gap between supply and demand (Akharume et al., 2021; Dupuis et al., 2023; Eastham and Leman, 2024; Gnaim et al., 2025; Kyriakopoulou et al., 2021; Nadar et al., 2024; X. Wang et al., 2025). Here can be found an example of a word cloud of the most frequently mentioned fermentation ingredient types in cellular agriculture (Fig. 1), based on the data extracted from companies worldwide actively contributing to advancements in the fermentation sector that focus on alternative proteins primarily. Collectively, these advancements promise the future of fermentation-enabled food production that is not only diverse and intelligent but also wholesome and sustainable (Cho et al., 2025; Hilgendorf et al., 2024), thereby facilitating the fulfillment of population-specific nutritional needs. .

This review aims to present comprehensive insights into precision fermentation intersecting cell-based production within the context of future food manufacturing globally, addressing how these technologies play a key role in addressing “hidden hunger” risk and achieving consumer insights-informed nutritional engineering by overcoming limitations of traditional fermentation. This clear research gap facilitates us to critically examine and integrate case studies and modeling analysis, as well as insights from synthetic biology and metabolic engineering, alongside the roles of CAE, AI, and automation in streamlining these processes. We highlight the significance of the developments in microbial strain development, bioprocess optimization, and pre- and post-fermentation processing techniques. Furthermore, we also examine how can CAE, AI, and automation-enabled precision fermentation technology provide innovative solutions for sustainable food production and the technical and industrialization challenges of scaling production, consumer acceptance issues, the regulatory landscape surrounding these emerging technologies, and the enhancements of food properties and nutrition, offering a comprehensive perspective on the future of food production through precision fermentation intersecting cell-based production.

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