Bridging agriculture, health and industry through plant molecular farming in the bioeconomic era

Every person deserves appropriate nutrition. Our world approaches a human population of 10 billion within the next 30 years, with global food demand increasing by more than 50% during this time period¹.

By 2050, global food demand is projected to increase by 50–60% compared to 2010 levels, with protein demand expected to double in some regions². This growing demand encompasses diverse nutritional needs, including high-energy staples such as rice, wheat, and maize to ensure calorie sufficiency; high-quality proteins from sources like meat, dairy, plant-based alternatives, and novel proteins to support nutrition security³; and high-value foods such as functional ingredients and specialty crops that contribute to economic diversification. Global food systems are undergoing an upheaval, with vulnerabilities such as economic shocks due to tariff changes, the risk of zoonotic infectious diseases such as bovine influenza in the US, and geopolitical conflict such as grain shortages due to the Russian- Ukraine war. Collectively, these disruptions have greatly affected food prices and availability⁴. However, scaling up supply across these categories is challenged by the impacts of climate change, dietary shifts driven by urbanization and rising affluence, as well as policy and trade uncertainties⁵.

In response, and due to concerns about global food security issues, many nations such as the US are trying to change the way they produce food, to mitigate global shocks of all nature, and to decentralize yet strengthen food supply chains to reduce their vulnerabilities⁶. The most noteworthy way this is taking place is by investing in novel strategies to produce alternative proteins. Alternative proteins, then, refer to those made that are equally as nutritious as conventional animal proteins, but are cheaper, require fewer inputs, have a lower carbon footprint, and are resilient to climate shocks⁷.

Alternative protein production should reduce the load of zoonotic diseases as well as agricultural pest pressures and other exacerbating problems associated with livestock production, ranging from antimicrobial resistance to animal cruelty, from fair trade to bioterrorism⁸. Decentralizing our food production to an abundance of smaller locations would mitigate these problems substantially. The overall effect will be a shift in trade relations from one that is fixed due to geography, to one that is fluid and unconstrained.

Alternative protein technologies for food are often placed into three main categories: cultivated meat, plant-based protein, and precision fermentation⁹. Cultivated, or cell-based meat, refers to the production of meat cells in culture to produce a food product such as hamburger, sausage or chicken nuggets. Plant-based proteins can be defined as proteins which have been processed in such a way that they resemble animal sourced products, such as oat milk. Precision fermentation covers the use of microbial fermentation systems to produce individual animal protein in a manner that more closely resembles the technology used in the past to produce pharmaceutical proteins. This synthetic biology approach includes the incorporation of a gene encoding an animal protein into the genome of a bacterial or fungal strain, which is then cultivated in a bioreactor to produce large amounts of target proteins, such as casein and whey. These three pillars represent the fundamentals of alternative protein production.

A fourth ‘pillar’ has been defined as a facet of cellular agriculture based on plant molecular farming and plant cell culture technologies. Plant molecular farming refers to the use of plants themselves to replace microbial bioreactors, in such a way that a gene of interest is expressed and extracted from plants instead of from microbes¹⁰. Plant cellular agriculture, on the other hand, makes use of plant cell culture to produce large amounts of plant biomass which can be processed into food products, analogous to some of the cultivated meat production technologies¹¹. Plant molecular farming and plant cell culture have been proposed as a potential “fourth pillar” of alternative proteins, though their precise definition and boundaries remain debated within the field.

The following Perspective presents various examples of this fourth pillar of alternative plant cell-based technologies and describes the advantages that it has over the others. The Perspective concludes with a prediction of the prospects of plant cellular agriculture to address the widening cracks found within our current food system.

Plant molecular farming can be defined as the use of plants as a production platform to express a target protein¹². Originally a production platform for pharmaceutical proteins (molecular pharming) that was developed over a quarter of a century ago, the technology has matured to such an extent that animal food proteins found in dairy, meat and eggs have become a more recent series of products under development. A great advantage of plant molecular farming is that in place of costly bioreactors, greenhouses or farm fields can be used to produce the protein of interest, thus mitigating the economic and environmental costs associated with farming livestock¹³. Plant molecular farming thus does not encounter scaling challenges the way other protein production platforms, such as precision fermentation, must face. Plants can perform post translational modifications that more resemble their animal counterparts, thus enabling them to follow a form and functionality that is superior to proteins produced in many microbial systems¹⁴. Animal proteins can be produced and stored in a wide diversity of plant tissues, such as potato tubers, rice grains, and legumes such as peas and soybeans¹⁵. Since these are edible tissues, it is feasible that partial purification of the protein in question may be sufficient, or, depending on the circumstances, completely unnecessary. Originally, this technology was adapted by companies such as Medicago, iBio and Kentucky Bioprocessing Co, to produce vaccines, monoclonal antibodies and other biologics¹⁶. Today, over 30 molecular farming companies can be found which produce different animal food proteins. Examples include Argentinian company Moolec (recently merged with Bioceres group limited), which produces the heme protein myoglobin in soybean and pea that can be processed into iron loaded products such as textured vegetable protein (valorasoy.com). Alpine Bio (formally Nobell Foods), based in San Francisco produces dairy proteins such as casein for cheese in soybean (alpbio.com). PoloPo is an Israeli company which produces the egg protein ovalbumin in potato tubers (PoLopo.tech). In Europe, molecular farming company Nambawan Spain produces and purifies sweet proteins such as thaumatin in transgenic tobacco seed (namba-wan.com).

The key steps to plant molecular farming include determining the appropriate mode of animal gene delivery to crops, then optimizing expression levels, scaling-up to produce the desired amount of protein and finally, purification of protein, if required. Animal genes can be introduced via stable transformation to produce transgenic plants, or transiently, using replicating constructs based on virus expression vectors¹⁷. To date, largely transgenic plants have been created which express the target protein; these crops can be produced in the field or greenhouse and the protein extracted using standard agricultural techniques. Limitations for these processes include regulatory issues for GMOs (for plants grown in the open field) and scale up limitations (for plants grown in the greenhouse). Transient expression performed in the greenhouse using virus expression vectors can increase yield considerably and can be introduced to field crops using novel spray technologies, which are currently under development¹⁸.

Expression levels can vary depending on the type of protein being produced (this problem exists for precision fermentation as well) and the tissue that it is expressed in, as well as environmental factors such as temperature and humidity. Oilseed crops, like soy, for example, have been shown to express myoglobin at 26.6% of the total soluble protein in the legume¹⁹; this can be easily stored at ambient temperatures and extracted later, whereas the level of protein expressed in a leafy crop like lettuce or tobacco may be considerably lower, but may not require extensive purification, depending on its future use. Existing agricultural infrastructure can be used whether the plants are produced in the greenhouse or in open field, and both farming practices can support local rural economies in a fashion that is more environmentally sustainable than livestock agriculture¹⁰.

A comparison between plant molecular farming and precision fermentation indicates that on average, plant molecular farming requires a much lower initial investment, Capex and scaleup costs than precision fermentation. Precision fermentation, on the other hand, has lower land use requirements but also relies on sugar and other carbon sources, as well as continuous power to run the bioreactors¹³. These limitations make it more challenging to scale up to global demand, due to the inhibitory costs of bioreactors and in fact sufficient access to global steel to produce them²⁰. While transgenic plants in the open field remain subject to GMO concerns (although protein purified from such sources is not considered to be a GMO), plants do not harbor mammalian pathogens and thus contain lower safety concerns than some microbial expression systems.

Artificial intelligence (AI) and machine learning (ML) are now accelerating breakthroughs in plant molecular farming by enabling high-throughput strain optimization, metabolic pathway prediction, and the identification of gene-editing targets^21,22. AI-driven algorithms are increasingly used to analyze large-scale omics datasets, predict optimal gene regulatory networks, and guide the design of synthetic constructs for enhanced metabolite production²³. For instance, deep learning frameworks can assist in optimizing codon usage, protein folding stability, and promoter strength for cell factory development in plants or plant cells. When combined with CRISPR-based genome editing, these tools can significantly reduce the trial-and-error cycle in engineering high-yielding production strains, paving the way for scalable and cost-effective plant-based biofactories. Integrating AI into strain design thus not only enhances precision and efficiency but also supports predictive modeling for sustainable and economically viable molecular farming systems²⁴.

Cellular agriculture, a rising field focused on producing a plant-based product directly from a single cell rather than using whole organisms in their natural habitat, offers a transformative approach for the sustainable production of ingredients used in food, cosmetics, and nutraceuticals¹¹. Within this framework, plant cell culture serves as a powerful platform for generating high-value bioactive compounds, flavors, pigments, and even staple ingredients through controlled, in vitro methods. Techniques such as micropropagation, adventitious shoot or root formation, and somatic embryogenesis are widely applied for the regeneration of whole plants and the production of targeted compounds from cultured cells²⁵. The commercialization of these processes using bioreactor systems helps overcome major limitations of conventional methods, which are often labor-intensive and difficult to scale. Bioreactors enable precise control of physical and chemical conditions, improve nutrient distribution, reduce physiological disorders such as hyperhydricity, and support automation, making large-scale production more efficient and economically viable²⁶.

Thus, plant-based cellular agriculture not only reduces reliance on land, water, and traditional farming practices, but also supports global efforts toward a circular and sustainable bioeconomy, where biologically derived, renewable resources drive industrial innovation, environmental sustainability, and inclusive economic growth²⁷.

Plant tissue culture involves the sterile cultivation of plant parts under controlled conditions, first conceptualized by Gottlieb Haberlandt in 1902, and based on his pioneering work with single-cell cultures²⁸. Initially developed at the beginning of the 20^th Century, plant tissue culture has come a long way since then, and includes technologies that make use of root cultures, embryonic cultures, and many others²⁹. Plant cell culture can assist in the production of a plethora of secondary metabolites, and their yields can be vastly improved using genome editing technologies for an increasing number of plant species³⁰. Resembling a cross between cell-based meat and precision fermentation in terms of technology, plant cell culture will facilitate the production of ingredients which would reduce supply chain disruptions. Today, plant cell culture can be produced in bioreactors as great as 100,000 L³¹.

The number of food products that can be produced in plant cell culture has exploded and will continue to expand as concerns about supply chain disruptions grow. For example, cocoa production in cell culture is now being explored as a viable option by several different cellular agriculture companies. Current cocoa production is restricted to tropical regions and is under pressure in terms of loss of land, human rights issues, pest pressures, and is not particularly environmentally friendly³². While these issues, when combined with predictive models of climate change, will undoubtedly reduce our future global cocoa supplies, the demand for cocoa is increasing at a rate that cannot be met using traditional manufacturing processes.

Plant cell culture technology is emerging as a transformative platform for the sustainable production of high-value food ingredients. Cultivation of specific plant tissues or cells in a controlled system bypasses traditional agricultural constraints such as seasonal variation, climate vulnerability, and ethical concerns related to labor practices.

A notable example is California Cultured (cacultured.com), a U.S.-based biotechnology company that is producing cocoa from cell cultures. Cocoa bean cell cultivation, rapid cell growth and maturation are all possible as well as scalable. This method also minimizes the use of water and labor. It avoids environmental and social issues commonly associated with cocoa farming in West Africa, where most global cocoa is sourced.

Due to increasing cocoa demand and the vulnerability of the supply chain, cell culture-based cocoa offers a scalable and ethical alternative, providing substantial reductions in land use, water consumption, and labor requirements compared to conventional cultivation. To truly understand whether plant-based or cell-culture cocoa is more sustainable, the industry needs to apply life-cycle assessment (LCA) more widely. Future LCA studies on chocolate should clearly define their system boundaries, select functional units that are relevant to the purpose, and, where possible, combine both established and newer assessment methods. Adding steps such as uncertainty and sensitivity analysis can help ensure that the results are not only accurate but also reliable for guiding decisions³³.

Beyond cocoa, similar cellular agriculture technologies are also being applied to coffee production. Arabica coffee is the most widely consumed variety, and is threatened by climate-induced stress and fungal pathogens³⁴. Pluri Biotech (pluri-biotech.com), an Israeli company, is developing coffee from plant cell cultures. Using bioreactors designed to support structured cell growth, the company cultivates coffee cells capable of synthesizing key bioactive compounds such as caffeine. The resulting biomass is harvested, dried, and roasted, yielding a product that visually and sensorial resembles conventional ground coffee.

In Europe, the French startup Stem (s-tem.fr) is also working with coffee cell cultures. The cultured coffee powder with natural flavor extracts derived from coffee processing byproducts creates a final product that maintains the sensory characteristics of traditionally harvested beans³⁵.

Like cocoa and coffee, cellular agriculture is now an attractive alternative for the production of other bioactive and commercially valuable compounds, including vanillin, saffron, natural colorants, flavor compounds, and dietary supplements³⁰. Growing consumer demand for traceable, sustainable and ethically produced food sources worldwide has fueled the development of plant cell-cultured products. Plant cell culture offers a promising platform for localized, scalable, and clean-label production of essential ingredients for food, cosmetics, and nutraceuticals, addressing both environmental challenges and evolving consumer expectations. Recent advances in plant cell culture and molecular farming are driving a growing number of startups to translate the science into commercial progress. These companies illustrate the technology’s potential through measurable funding rounds, strategic partnerships, and scale-up milestones (Table 1).

Plant cell culture offers reduced land use and zero exposure to pests compared to open-field agriculture; however, it requires substantial energy, high-purity water, and refined media components, including sucrose and hormones, enabling the development of heterotrophic cultures. Life-cycle assessments indicate that although emissions per biomass unit may be lower, energy consumption remains a key barrier to economic scalability without renewable energy and media recycling^15,36. Techno-economic analyses further emphasize electricity and sugar sourcing as critical factors that need optimization for commercial viability³⁷.

Regulatory frameworks remain a critical consideration for the deployment of products derived from plant biotechnology. While open-field genetically modified (GM) crops typically undergo approval through distinct regulatory pathways, such as the Novel Food Regulation of European Union (EU 2015/2283) and the U.S. FDA approved Generally Recognized as Safe (GRAS) process, plant cell culture–derived products from controlled environments may follow different routes with unique timelines, transparency requirements, and public consultations³⁸. Moreover, societal concerns regarding “laboratory-grown” or “genetically modified” ingredients could impact consumer acceptance and market adoption, highlighting the importance of proactive engagement and clear communication strategies to address public perception and ethical considerations³⁹. Specifically, the molecular farming of animal proteins in plants raises additional public health, stewardship, religious, and ethical questions, underscoring the need for collaborative dialog among scientists, regulators, industry, and religious leaders to ensure responsible development and societal acceptance⁴⁰.

The rise of cellular agriculture and plant molecular farming has the promise to transform global food systems by producing high-quality alternative proteins and novel ingredients with reduced land and water demands. The success of this growth is hindered by the cost, scalability, consumer acceptance, technical, regulatory, and societal hurdles. Life-cycle assessments and policy frameworks can facilitate the adoption of these technologies, which can complement alternative protein, fermentation, and conventional agriculture to form a resilient and diversified landscape of plant-based products. Strategic innovation, integrating advanced breeding, AI-driven optimization, genome editing, or other breakthrough modern technologies, helps scientists select better cell lines, tweak metabolic processes, and automate production steps, along with supportive policy, to accelerate their path to scale. Combining these advances as part of sustainable food production will ensure they complement, rather than compete with, other alternative protein pillars, positioning them to play a decisive role in meeting the nutritional and environmental challenges of the coming decades for both people and the planet.