21EngBio: Organelle engineering for the production of useful bioproducts

本氏烟草是一种类似于烟草的植物。某些农杆菌菌株(一种土壤细菌)可以携带或感染本氏新月杆菌，并瞬时表达基因，形成基于蛋白质或代谢产物的产品。寄主N.benthamiana品系的效率或性能对所生产产品的产量和质量起着重要作用。到目前为止，N.benthamiana细胞工厂造福人类的主要产品是蛋白质，包括疫苗成分和抗体。叶绿体是光合作用植物细胞中的关键结构，对植物的功能至关重要。叶绿体中存在特定的生化途径，因此某些有价值的化学物质只在叶绿体中产生。在叶绿体中进行的代谢也驱动植物的新陈代谢。叶绿体也代表一种细胞结构，可以用来储存或储存化学物质(代谢物)。在N.benthamiana中也存在产生小分子(代谢物/化学物质)的潜力。在许多情况下，这将改善生产的环境资质，因为目前化学合成主要使用来自石化精炼工业的前体。我们日常使用的许多有价值的植物来源的代谢物和前体都是在叶绿体中合成或储存的。叶绿体还通过其独特的新陈代谢为细胞提供重要的能量。在目前的项目中，我们雄心勃勃的目标是创造出具有更多叶绿体的细胞。因此，将产生每个细胞含有更多叶绿体的本氏新月藻品系。细胞叶绿体补充量的增加将通过调节感知光量的调节器来实现。实际上，工厂将被打开，以始终体验光线入射。创建稳定的品系将产生更多的叶绿体，这将使它们能够作为宿主产生其他有价值的小分子。在该项目中，我们将证明创建的植物可以作为更有效的宿主来生产虾青素和角鲨烯。这些都是有价值的生物合成相关分子，可用于多个工业部门。虾青素是一种有价值的饲料添加剂，可用于水产养殖和家禽饲料中。它负责给鲑鱼/鲑鱼的肉和鸡的蛋黄赋予颜色。没有这种颜色，所产生的产品就不能出售。角鲨烯用于个人护理产品，是疫苗的主要佐剂。目前，随着严重急性呼吸综合征冠状病毒2(SARS-CoV-2)疫苗的快速开发和生产，疫苗生产是至关重要的，因此它是一种需求量很大的商品。目前角鲨烯的主要来源是鲨鱼的肝脏。供不应求，而且在这两种情况下，生产方法都缺乏环保资质。因此，交付新的植物细胞工厂代表了一种新的可持续生产方法。

Nicotiana benthamiana is a plant similar to tobacco. Certain strains of Agrobacterium (a soil bacteria) can be taken up or infect N. benthamiana and express genes transiently to form protein or metabolite based products. The efficiency or properties of the host N. benthamiana line play a major role in yield and quality of the products produced. To date the main products from the N. benthamiana cell factory that have benefited humanity have been proteins, including vaccine components and antibodies.Chloroplasts are key structures within photosynthetic plant cells that are essential for the functioning of the plant. Specific biochemical pathways exist in the chloroplasts and thus certain valuable chemicals are only generated in the plastid. The metabolism performed in the chloroplast also drives the metabolism of the plant. The chloroplast also represents a cellular structure that can be used to store or deposit chemicals (metabolites). The potential exits to also produce small molecules (metabolites /chemicals) in N. benthamiana. This would in many cases improve the environmental credentials of production as presently chemical synthesis, using precursors derived from petrochemical refining industry are used predominantly. Numerous valuable plant derived metabolites and precursors that we use daily are synthesised or stored in the chloroplast. The chloroplast also provides vital energy for the cell through its unique metabolism. In the present project our ambitions goal is to create cells with more chloroplasts. Thus, lines of N. benthamiana will be generated that contain more chloroplasts per cell. The increase in the chloroplast complement of the cell will be achieved by modulating regulators that perceive the quantity of light. Effectively the plant will be switched on to experience light incidence all the time. Creating stable lines will generate more chloroplasts which will enable them to act as hosts to produce other valuable small molecules.In the project we will demonstrate that the plant created can act as a more efficient host to produce Astaxanthin and Squalene. These are valuable biosynthetically related molecules that are used across multiple industrial sectors. Astaxanthin is a valuable feed additive that is incorporated into aquaculture and poultry feeds. It is responsible for conferring the colour to the flesh of salmon/trout and the egg yolks of chickens. Without this colour the produce generated cannot be sold. Squalene is used in personal care products and is the leading adjuvant for vaccines. Presently, it is a commodity in great demand as vaccine production is paramount with the rapid development and production of vaccines against sever acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The present major source of squalene is shark's liver. Demand is outstripping supply and in both cases and production methods have poor environmental credentials. Thus, delivery of new plant cell factories represents a new sustainable production method.