As the demand for sustainable, scalable and ethical food sources grows, molecular farming and plant cell cultivation emerge with potential to redefine the global food system. Molecular farming leverages plants as advanced biofactories to produce proteins, while plant cell cultivation optimises controlled cellular environments to synthesise food components and bioactive compounds. In this feature, we explore how these technologies address environmental and ethical challenges while catering to the evolving needs of the food industry.
What’s the difference?
Molecular farming and plant cell cultivation are both advanced methods in biotechnology for producing valuable compounds, but they differ in their approaches and applications:
Molecular farming
Process: Molecular farming involves genetically modifying plants to produce specific proteins, enzymes or other high-value compounds (eg. nutritional supplements or pharmaceuticals). This is often done by inserting genes into the plant's DNA, instructing it to produce the desired compound as it grows.
Applications: Used in the food-tech space to produce animal-free proteins, for example producing essential growth factors in bioengineered barley plants
Advantages: Low-cost and large-scale production potential, as plants can be grown in fields or controlled environments. Also, it can scale up without the need for high-tech fermentation facilities.
Plant cell cultivation
Process: Plant cell cultivation grows specific plant cells or tissues in controlled laboratory conditions, often in bioreactors. Unlike molecular farming, this doesn’t involve whole plants; instead, plant cells are cultured to produce particular bioactive compounds, using plant tissues that are rich in these compounds.
Applications: Used to produce botanical and food ingredients, as well as to enhance specific characteristics, such as increasing the protein content of compounds naturally found in certain plant cells.
Advantages: Allows precise control over production and purity, as the cells are cultivated in highly regulated conditions. It also bypasses issues related to agricultural factors like seasonality or crop failures.
Key differences
Genetic modification: Molecular farming usually involves genetically modifying plants, while plant cell cultivation may not require genetic modification, as it leverages the natural ability of plant cells to produce desired compounds.
Scale and environment: Molecular farming typically grows whole plants, often outdoors, while plant cell cultivation uses controlled, sterile environments to culture cells in bioreactors.
Application areas: Molecular farming is more geared toward protein-based products, such as producing casein in agricultural seeds, while plant cell cultivation is suited for secondary metabolites, for example, it allows for the creation of high-quality coffee compounds from a select few cells of coffee beans.
Both approaches provide sustainable, scalable alternatives to traditional agricultural and industrial methods, presenting valuable opportunities for the food sector, along with applications in the pharmaceutical and cosmetic industries.
Company spotlights
On the following pages, we spotlight ten pioneering companies advancing molecular farming and plant cell cultivation, showcasing their innovative approaches to addressing the global food system's most pressing challenges./
Molecular farming
Evogene
Founded in Israel in 2002, Evogene is focused on developing sustainable, animal-free proteins through the use of advanced AI-driven computational biology. “Our overall vision is to improve food security and reduce the environmental impact of livestock by developing more sustainable and cost-effective crop-bred, animal-free proteins for meats and dairy,” Eyal Ronen, EVP of business development at Evogene, told The Cell Base.
Evogene is currently concentrating on the production of casein, a key protein in dairy products, through the cultivation of genetically modified potatoes. This approach enables the production of cheese without relying on cows.
Evogene's innovative process leverages an extensive database of microbes and small molecules, integrating this information with advanced machine learning algorithms. These algorithms assess a range of parameters tailored to specific research inquiries, streamlining the screening process considerably when compared to traditional candidate sequencing methods. This sophisticated approach allows for the rapid identification of the most promising candidates, significantly enhancing the efficiency of bringing viable commercial products to market.
In April, Evogene, in collaboration with Israel’s Strauss Group’s food-tech incubator, The Kitchen FoodTech Hub (TKH), announced the launch of a new venture called Finally Foods. Specialising in molecular farming for the food sector, Finally Foods focuses on delivering sustainable, alternative sources of animal-based proteins. Evogene retains a 40% ownership stake in the new company, with TKH and the founding team – CEO Dafna Gabbay and CTO Basia Vinocur – holding the remaining shares.
NewMoo
Founded in 2021, Israeli start-up NewMoo has developed a platform for producing casein in agricultural seeds – a technique called plant molecular farming. Casein is essential for recreating the sensory experience of traditional dairy cheese. “Until now, cheese alternatives have struggled to offer consumers the real cheese experience, nutrition and price,” explained Daphna Miller, NewMoo’s CEO. “These cheese analogues do not contain the key dairy proteins – caseins – necessary to precisely recreate the sensory properties of dairy cheese.”
NewMoo’s approach solves this problem by producing a liquid casein base that mirrors the functionality of cow’s milk. “Our animal-free liquid casein mimics all the functional traits of real milk protein for crafting cheese the traditional way,” Miller added. “It can seamlessly replace dairy milk in any cheese manufacturing facility without the need for special equipment, maintaining the typical aroma, flavour and texture that cheese eaters crave."
The start-up’s technology was built out of research conducted at the Weizmann Institute of Science, in Rehovot, Israel. The platform allows for the expression of two or more caseins within a single plant. The seeds are sown in outdoor fields, and after harvesting the plants, the casein is extracted through a unique development process, yielding a hormone-free, lactose-free and cholesterol-free liquid casein base.
This base replicates the functionality of dairy cheese, providing the same melt, stretch, and texture as traditional products. “Our animal-free proteins are identical to animal-derived caseins,” Miller commented. “For these reasons, our go-to-market is mozzarella for the pizza industry.”
Unlike precision fermentation practices, NewMoo’s plant molecular farming approach uses plant seeds as bioreactors and leverages open fields as production lines, reducing costs while offering the flexibility to produce these complex proteins at scale.
ORF Genetics
Established in Iceland in 2001, ORF Genetics manufactures recombinant proteins, including essential growth factors, through bioengineered barley plants. The company has pioneered several innovations within the molecular farming sector. Its plant-based protein production platform employs bioengineered barley seeds as a production host, and enables a cost-effective, scalable and sustainable method for generating high-purity speciality proteins, such as growth factors.
Additionally, ORF Genetics has developed advanced seed technology designed to enhance yield. Its optimised barley seed production techniques maximise the output of target proteins while minimising environmental impact. This technology facilitates cultivation in geothermal greenhouses and supports in-field cultivation at scale.
The company's rigorous purification processes employ advanced methods to guarantee that its speciality proteins meet the highest quality and purity standards, making them suitable for sensitive applications like cell culture media. Furthermore, ORF Genetics can adapt its processing techniques to better suit food production needs, including the creation of cultivated meat or fish.
“Using gene technology, our process begins with bioengineering the barley plant to produce the speciality protein in the seed,” Björn Örvar, ORF Genetics’ co-founder, CSO and EVP of business development, said. “These bioengineered plants are then scaled up in geothermal greenhouses in Iceland before harvesting. For some speciality proteins, we also use infield cultivation for large-scale production. After harvest, the seeds undergo a series of extraction and purification steps to isolate the target proteins, ensuring they meet high-quality and purity standards.”
In the cellular agriculture space, the firm has developed MESOkine animal growth factors designed to facilitate the large-scale production of cell-based meat and fish. “Our production of MESOkine is highly scalable and economical and can help our clients to bring down the cost of their production,” Örvar added. “We also produce SAPORkine, various taste management proteins such as sweeteners, that can be produced at scale in our barley seeds.”
PoLoPo
Israeli molecular farming start-up PoLoPo uses genetic engineering to produce proteins in potato plants. The start-up has created a new strain of potatoes that can produce egg protein, or ovalbumin, that is identical to chicken egg protein.
PoLoPo’s SuperAA platform enhances the production of targeted functional proteins in potato plants. The platform improves the plant’s amino acid metabolism – crucial for effective protein synthesis – in the storage organ, known as the tuber. Amino acids are efficiently transported to and concentrated in the potato tuber, where they facilitate the increased production of PoLoPo’s target protein – the firm is starting with ovalbumin.
PoLoPo’s ovalbumin is a one-to-one replacement for egg protein powders, which are widely used for enhancing nutritional value, increasing shelf life and for its functional properties such as texture and stability. In addition to ovalbumin, PoLoPo has successfully increased the native protein content of patatin – a non-allergenic protein used in a range of food products, including plant-based meats and dairy alternatives, baked goods, cereals, snacks, beverages, sports nutrition and nutraceuticals.
“Putting it briefly, we insert a DNA sequence into the potato plant’s genome,” Raya Liberman-Aloni, PoLoPo’s CTO, told The Cell Base. “When appropriately expressed in the right tissue and at the right time (our secret sauce), the plant produces the protein we are interested in, and it accumulates in the potato tuber. Plants are ‘trained’ to produce the protein we want and grow as typical potato plants. The potato tubers are harvested, the proteins are extracted using traditional potato processing lines and are then dried into powder.”
The flexibility of PoLoPo’s platform allows for its application to other food ingredients as well. “We’ve started with ovalbumin, but other animal proteins, notably dairy protein, can be produced on the SuperAA platform,” Liberman-Aloni concluded.
Plant cell cultivation
California Cultured
Through plant cell cultivation, US food-tech start-up California Cultured is pioneering the production of cocoa- and coffee-based products. “Our plant cell culture technology allows us to produce cocoa and coffee products that have identical characteristics to any chocolate bar or cup of coffee you will find at the store down to the very last molecule,” California Cultured CEO Alan Perlstein said.
“We select cacao and coffee varieties with the best flavour and health properties, take a handful of cells from them, and grow the cells as we equip them with plant nutrients in our low-cost reactor systems. Then our cells are harvested, fermented and roasted to create the cleanest and most delicious chocolate and coffee products ever made.”
California Cultured’s technology enables the company to grow ‘infinite’ amounts of bean tissue, very quickly and efficiently in a small space, rather than relying on favourable weather and labour, without waiting the five years it typically takes for a cacao tree to start producing cocoa.
“We have developed an extremely high-flavanol cocoa powder line, an ingredient recognised by the FDA to reduce the risk of cardiovascular disease,” Perlstein added.
“Also, we can grow real chocolate without lead or cadmium, and we are the first plant cell culture company to be able to produce cocoa butter. Cocoa butter is an essential ingredient for chocolate, but fats have been very difficult to produce in plant cell culture. Because we have been able to unlock cocoa butter production, we will be able to call our products chocolate.”
Pluri
Israeli biotech firm Pluri is advancing sustainable food production through its proprietary 3D cell expansion platform, which enables the large-scale production of bioactive compounds.
“Cultivation of plant cells in a controlled environment offers unique advantages, including a safer and more efficient platform for producing a range of plant metabolites,” Nimrod Barzvi, Pluri’s chief commercial and marketing officer, explained. “PluriAgtech offers cell-based solutions to optimise crop yields, create more resilient plants and deliver plant-based bioactive compounds for nutritional purposes.”
Pluri’s proprietary 3D cell cultivation platform mimics the natural function of plant cells by creating a suitable environment for cell growth and produces a wide range of compounds that are typically difficult to manufacture by conventional methods. “Our goal is to make farming more productive, reduce its environmental footprint and foster harmony between agriculture and nature,” Barvzi added.
The firm’s proprietary bioreactor system allows full control over all parameters in a unified manner for cells to grow – the way they are used to in agriculture. The cells start secreting bioactives that can be scaled up in Pluri’s modular Matrix bioreactor. Inside this closed, fully automated system, all critical parameters are controlled throughout the growth cycle, and conditions can be adapted to many types of plant cells and applications.
“For example, our cell-based coffee uses a very small amount of coffee plant that could replace 1,000 plants in the field,” Barvzi pointed out. “Plus, our coffee is ready in three weeks, rather than waiting for trees to produce a crop twice a year.”
Novella
Israeli biotech firm Novella uses plant cell cultivation to grow botanical ingredients without the need for the entire plant. The start-up has developed unique protocols and specialised media to activate various metabolic pathways within plant cells.
This approach allows the company to maximise the value of the entire plant cell rather than isolating just one component. Additionally, it has engineered a semi-continuous process, coupled with a newly designed bioreactor system, that enhances efficiency and scalability. "Our technology keeps the plant cells intact, preserving their full nutritional potential and ensuring a high-value product that stands out in the market,” Itay Dana, Novella’s co-founder and chief business development officer, told The Cell Base.
Novella's flagship products are derived from nutrient-rich plants, including berries, tomatoes and kale, particularly focusing on whole-berry formulations. These products come in powdered form, containing a full spectrum of bioactive compounds, such as polyphenols, carotenoids, vitamins and proteins. The applications of these ingredients span various sectors, including sports nutrition and natural preservation systems, promoting overall health and wellness.
“Our process starts with collecting plant tissues from various parts of the plant and different maturity stages,” Dana explained. “These tissues are then cultured in specialised media in our lab, leading to a liquid plant-cell suspension where the cells grow efficiently. This method shortens propagation time and boosts the concentration of bioactive compounds. The cells are then scaled up in bioreactors, harvested and dried, ensuring high-quality, nutrient-rich plant-based ingredients.”
Ayana Bio
Spun off from Ginkgo Bioworks in 2021, Ayana Bio leverages plant cell culture technology to produce bioactive ingredients that support health and wellness.
Ayana Bio’s process is meticulously designed to optimise bioactive production. It begins with growing authenticated plants in the lab, followed by sampling and sterilising plant materials. The excised tissues are placed in a nutrient-rich culture medium, crucial for cell division and de-differentiation to form a callus. This liquid suspension allows for precise control over growth conditions, including temperature, pH, aeration and elicitors. The use of high-throughput technologies, such as multi-omics, facilitates the identification of the most promising cell lines for specific bioactives.
Frank Jaksch, CEO of Ayana Bio, told The Cell Base: “Our ingredient portfolio includes popular health and wellness ingredients like echinacea, known for its immune benefits, lemon balm, which supports sleep and mood support, and sage, which boosts a healthy inflammatory response and cognitive support, as well as emerging plants such as dog rose and hedge nettle.”
Ayana Bio differentiates itself by leveraging high-throughput synthetic biology capabilities, including genetic sequencing and analytical chemistry, to optimise plant cell lines. This unique approach allows it to analyse hundreds of plant cell lines simultaneously, identifying the most promising candidates for commercial production.
Reagenics
In August, Israeli biotech start-up ReaGenics achieved a significant milestone by developing potato biomass with a protein content of 31% through cell cultivation. Traditionally, potatoes contain only about 2% protein and are not regarded as a viable protein source.
“We’re developing cutting-edge bioreactor technology that supports large-scale production of plant-based proteins and compounds,” highlighted ReaGenics’ CEO Eran Lagon. “We're also performing the research for the plants that we believe to have the most impact, like potatoes.”
ReaGenics grows plant cells in bioreactors, supplying them with a balanced mix of sugars, vitamins, minerals and nutrients to ensure a consistent production of plant compounds.
The process integrates AI to optimise the growth conditions of plant cells, supported by continuous feedback from the growth environment. “This approach allows us to consistently produce high-quality ingredients at scale,” Lagon noted.
The functional properties of ReaGenics' potato protein – including solubility, gelling, foaming and emulsification – make it highly versatile. The non-GMO protein includes all essential amino acids and has a PDCAAS score of 0.99, which makes it suitable for a wide range of food applications.
Best of both worlds
Ginkgo Bioworks operates in both the molecular farming and plant cell cultivation spaces.
Founded in 2008 in Boston, the company uses its synthetic biology platform to aid customers in the development of functional proteins, enzyme biocatalysts, small molecule ingredients and microbial strains, serving a variety of applications in the nutrition and wellness industries.
Ginkgo’s platform equips clients with essential tools to mitigate risks associated with research and development projects, streamlining the innovation process. "The breadth of our experience is really important here,” Patrick Boyle, Ginkgo Bioworks’ chief scientific officer, told The Cell Base. “We can bring in domain expertise that would be expensive or impractical for a customer to bring on for a single project."
The company recently collaborated with GreenLab to grow brazzein, a low-calorie sweetener protein, in corn, showcasing its capabilities in molecular farming. Simultaneously, Ginkgo's advanced plant cell cultivation techniques enable efficient protein expression and growth, allowing clients to leverage the significant biomass of engineered plants.
Ginkgo's approach integrates innovative technologies, including a reconfigurable automation system and high-throughput data generation capabilities, which streamline R&D processes. The company's extensive strain library and screening capabilities facilitate the discovery of valuable plant traits. By optimising gene sequences for efficient expression, Ginkgo can enhance protein yield in both plants and microbial systems.
#TheCellBase #molecularfarming #plantcellcultivation #biotech
