Towards massive scale-up of low-cost growth factor production for meat cultivation

工业化畜牧方法与不期望的环境影响相关，包括温室气体排放、高水/土地使用和动物福利/公共卫生问题，例如过度使用抗生素和人畜共患病。预计到2022年11月15日，全球人口将达到80亿，到2050年将达到100亿。有限的资源和全球肉类消费的增加为全球粮食不安全创造了条件。因此，肉类替代品的工业化需要营养蛋白质生产技术的成本效益和颠覆性创新。这种向种植肉类（CM）生产的转变将破坏这一极具价值的全球产业（2021年牛肉价值4670亿美元）。CM是使用组织工程方法在生物反应器中从动物干细胞生长的肉。干细胞在含有 ** 生长因子 **（**GF**）蛋白质的专门营养丰富的细胞培养基中分化成肉类中发现的细胞类型，如肌肉和脂肪。这些细胞与支架结合形成肉制品。因此，CM是在受控环境中生产的，而不需要饲养动物作为食物，减轻了与传统农业相关的许多问题。** 然而，经济可行性和规模扩大是采用和公众接受CM的主要障碍。** 主要成本驱动因素 ** 是培养基的 **GF组分 **。现有的GF蛋白生产和分离方法（关键的纯化步骤）对于从实验室到商业生产规模的转变是极其昂贵的。实际上，建模研究显示，目前使用生长因子FGF-2的CM生产成本在每公斤50，000 -400，000美元之间，在20，000 L生物反应器中的成本为5，000美元/mg。只有将FGF-2降低到名义成本，我们才能接近每公斤2美元的商品价格。** 我们的愿景是瞄准这一瓶颈，大规模扩大肉类种植的低成本增长因子生产 **。为了生产低成本的GF，我们将部署我们基于植物的GF批量表达平台，并将联合收割机与新的低成本替代品结合用于生物分离/纯化。这是通过利用可持续商业化的工业食品级底物的廉价方法实现的。中试数据表明，这是一种有效的纯化粗蛋白提取物的方法，具有高的生物活性回收率。预计GF生产的成本将大幅降低，这将带来深远的商业、经济、可持续性和环境影响。

Industrial livestock farming methods are associated with undesirable environmental impacts including greenhouse gas emissions, high water/land usage, and animal welfare/ public health concerns such as overuse of antibiotics and zoonoses. The worldwide population is expected to reach 8 billion by 15/11/2022, and 10 billion by 2050\. Finite resources and increasing worldwide meat consumption create conditions for global food insecurity. Cost-effective, disruptive innovations in production technology for nutritional proteins are therefore required for the industrialization of meat alternatives. Such a shift to **cultivated meat** (**CM**) production will disrupt this highly valuable global industry ($467 billion for beef in 2021). CM is meat grown from animal stem cells in a bioreactor using tissue engineering approaches. Stem cells are differentiated into cell types found in meat such as muscle and fat in specialized nutrient-enriched cell culture medium containing **growth factor** (**GF**) proteins. These cells are combined with scaffolds to form meat products. Thus, CM is produced in a controlled environment without farming animals for food, mitigating many of the concerns associated with conventional farming. **However, economic feasibility and scale-up are major barriers to the adoption and public acceptance of CM.** **Key cost drivers** are the **GF components** of culture media. Existing GF protein production and separation methods (a critical purification step) are prohibitively expensive to transition from laboratory to commercial production scale. _Indeed, modelling studies show current CM production costs between $50,000-400,000USD per kg using the growth factor FGF-2, at a cost of $5,000/mg in a 20,000L bioreactor. Only by reducing FGF-2 to nominal costs can we approach commodity level prices of $2 per kg._ **Our vision is to target this bottleneck enabling massive scale-up of low-cost growth factor production for meat cultivation**. To generate low-cost GFs, we will deploy our plant-based GF bulk-expression platform, and combine with novel low-cost alternatives for bioseparation/purification. This is achieved using an inexpensive approach exploiting sustainable commercially-available industrial food-grade substrates. Pilot data has shown this is an effective method for purifying crude protein extracts with high recovery of biological activity. Significant cost reductions for GF production are envisaged, with profound commercial, economic, sustainability and environmental impacts.