Increases in global meat demands cannot be sustainably met with current methods of livestock farming, which has a substantial impact on greenhouse gas emissions, land use, water consumption, and farm animal welfare. Cultivated meat is a rapidly advancing technology that produces meat products by proliferating and differentiating animal stem cells in large bioreactors, avoiding conventional live‐animal farming. While many companies are working in this area, there is a lack of existing infrastructure and experience at commercial scale, resulting in many technical bottlenecks such as scale‐up of cell culture and media availability and costs. In this study, we evaluate theoretical cultivated beef production facilities with the goal of envisioning an industry with multiple facilities to produce in total 100,000,000 kg of cultured beef per year or ~0.14% of the annual global beef production. Using the computer‐aided process design software, SuperPro Designer®, facilities are modeled to create a comprehensive analysis to highlight improvements that can lower the cost of such a production system and allow cultivated meat products to be competitive. Three facility scenarios are presented with different sized production reactors; ~42,000 L stirred tank bioreactor (STR) with a base case cost of goods sold (COGS) of $35/kg, ~211,000 L STR with a COGS of $25/kg, and ~262,000 L airlift reactor (ALR) with a COGS of $17/kg. This study outlines how advances in scaled up bioreactors, alternative bioreactor designs, and decreased media costs are necessary for commercialization of cultured meat products.
Transgenic plant cell cultures offer a number of advantages over alternative host expression systems, but so far relatively low product concentrations have been achieved. In this study, transgenic rice cells are used in a two‐compartment membrane bioreactor (CELLine 350, Integra Biosciences) for the production of recombinant α‐1‐antitrypsin (rAAT). Expression of rAAT is controlled by the rice α‐amylase (RAmy3D) promoter, which is induced in the absence of sugar. The extracellular product is retained in the bioreactorapos;s relatively small cell compartment, thereby increasing product concentration. Due to the packed nature of the cell aggregates in the cell compartment, a clarified product solution can be withdrawn from the bioreactor. Active rAAT reached levels of 100–247 mg/L (4–10% of the total extracellular protein) in the cell compartment at 5–6 days postinduction, and multiple inductions of the RAmy3D promoter were demonstrated.
Direct gene synthesis is becoming more popular owing to decreases in gene synthesis pricing. Compared with using natural genes, gene synthesis provides a good opportunity to optimize gene sequence for specific applications. In order to facilitate gene optimization, we have developed a stand-alone software called Visual Gene Developer.
Continuous reports of foodborne illnesses worldwide and the prevalence of antibiotic‐resistant bacteria mandate novel interventions to assure the safety of our food. Treatment of a variety of foods with bacteriophage‐derived lysins and bacteriocin‐class antimicrobial proteins has been shown to protect against high‐risk pathogens at multiple intervention points along the food supply chain. The most significant barrier to the adoption of antimicrobial proteins as a food safety intervention by the food industry is the high production cost using current fermentation‐based approaches. Recently, plants have been shown to produce antimicrobial proteins with accumulation as high as 3 g/kg fresh weight and with demonstrated activity against major foodborne pathogens. To investigate potential economic advantages and scalability of this novel platform, we evaluated a highly efficient transgenic plant‐based production process. A detailed process simulation model was developed to help identify economic “hot spots” for research and development focus including process operating parameters, unit operations, consumables, and/or raw materials that have the most significant impact on production costs. Our analyses indicate that the unit production cost of antimicrobial proteins in plants at commercial scale for three scenarios is $3.00–6.88/g, which can support a competitive selling price to traditional food safety treatments.
Transgenic rice cell cultures, capable of producing recombinant human α 1 ‐antitrypsin (rAAT), were scaled up from shake flasks to a 5‐L bioreactor. The maximum specific growth rates (μ max ) observed from two bioreactor runs were 0.40 day −1 (doubling time of 1.7 days) and 0.47 day −1 (doubling time of 1.5 days), and the maximum specific oxygen uptake rates were 0.78 and 0.84 mmol O 2 /(g dw h). Using a metabolically regulated rice α‐amylase (RAmy3D) promoter, signal peptide, and terminator, sugar deprivation turned on rAAT expression, and rAAT was secreted into the culture medium. After 1 day of culture in sugar‐free medium, there was still continued biomass growth, oxygen consumption, and viability. Extracellular concentrations of 51 and 40 mg active rAAT/L were reached 1.7 and 2.5 days, respectively, after induction in a sugar‐free medium. Volumetric productivities for two batch cultures were 7.3 and 4.6 mg rAAT/(L day), and specific productivities were 3.2 and 1.6 mg rAAT/(g dw day). Several different molecular weight bands of immunoreactive rAAT were observed on immunoblots.