This week I am exploring a topic called plant molecular farming.
Background about this technology: Plant molecular farming refers to the production of recombinant proteins in plants. The process begins by inserting the desired protein DNA into the plasmid of a plant cell. Seeds are subsequently grown into transgenic plants (plants that contain foreign DNA). Once grown, either the leaves or the seeds of the plants may be harvested and are ready to undergo downstream processing to recover the protein product. (Buyel JF – Plant Molecular Farming – Integration and Exploitation of Side Streams to Achieve Sustainable Biomanufacturing. Front Plant Sci. 2019;9:1893. Published 2019 Jan 18)
- This is a complex process that requires separation of the desired protein from all impurities, plant secondary metabolites.
Molecular Farming is an alternate approach to inserting protein DNA into a prokaryotic organism such as a yeast or bacteria cell and fermenting the organism inside of a bioreactor system.
- Transgenic plants actually serve as a single use bioreactor system and become the workhorse for protein production rather than a yeast or bacteria cell that is fermented in a microbial production system.
- This approach eliminates the need for bioreactor manufacturing systems while still employing recombinant protein technology to express specific high value compounds that can be used for a range of applications such as vaccines, cosmetics, biofuels, industrial enzymes, medications, and more recently food ingredients.
Why We Care: This technology may prove to be just what cellular agriculture needs to reduce the high cost of growth factors needed in significant quantities to produce cell cultured meat. Currently, growth factors are estimated to make up ~80% of the cost of production of cell based meat.
I spoke with legacy plant molecular farming company based in Iceland, ORF Genetics about the company’s recent 2.5 million Euro research and innovation grant from the European Union to pursue development of growth factors for cell based meat under the product line MESOkine.
ORF Genetics has been using barley seeds to synthesize high value proteins since its founding in 2001. The barley seeds serve as a self-contained bioreactor to protect the genetic sequence that has been engineered to synthesize specific proteins.
ORF Genetics has primarily been producing human growth factors for stem cell research and the skin care industry (check out their hero ingredient Epidermal Growth Factor). The company has now recognized a major opportunity in leveraging their experience and know-how in mammalian stem cell growth factors for the burgeoning cell based meat market.
The platform will kick off with a strong pipeline of growth factors including EGF, FGF BASIC, IGF-1, IL-6, KGF, LIF, VEGF 165.
I spoke with company Co-Founder, CSO & EVP of Research & Innovation Dr. Björn Lárus Örvar about the advantages of this technology compared to fermentation systems and he shared the following
- The plant based system does not require a build out of costly bioreactor systems.
- The plant based system can be scaled quickly and to agricultural scales. Plants can be cultivated on an agricultural scale to yield 100–1000 kg of the pure protein per year. (Fischer, Rainer & Buyel, Johannes, 2020, Molecular farming – The slope of enlightenment. Biotechnology Advances. 40. 107519.0.1016/j.biotechadv.2020.107519.)
- ORF Genetics has identified native proteins inside of the barley seed that can be included in the final growth factor to stabilize and improve the efficiency of the growth factor impact on stem cell proliferation and differentiation
Barley Seed is Key to ORF Genetics platform for producing food grade components because it already has the GRAS certification. Additionally, the barley seed platform has some unique advantages in the food grade production system
- Streamlined downstream processing because most of the impurities are in the seed coat which is easier to purify compared to other plant molecular farming systems such as tobacco leaves
- Once the seeds are harvested they can be stockpiled and stored indefinitely prior to downstream processing to extract growth factors → this is a huge advantage in establishing a stable and reliable supply for growth factors for cellular agriculture
In addition to growth factors ORF Genetics is looking to build out a larger portfolio of food based proteins (think hemoglobins) and taste modifying proteins (think proteins that remove bitter off notes or improve sweetness → These proteins have a wide range of applications from plant based meat to low calories sweeteners.
Bottom Line: Barley seeds may quite literally hold the key to unlocking valuable cellular agriculture inputs, which can improve food security and stability of the supply chain for important cell growth factors.
