Rational domestication of a plant-based recombinant expression system expands its biosynthetic range

Plant molecular farming aims to provide a green, flexible, and rapid alternative to conventional recombinant expression systems, capable of producing complex biologics such as enzymes, vaccines, and antibodies. Historically, the recombinant expression of therapeutic peptides in plants has proven difficult, largely due to their small size and instability. However, some plant species harbour the capacity for peptide backbone cyclization, a feature inherent in stable therapeutic peptides. One obstacle to realizing the potential of plant-based therapeutic peptide production is the proteolysis of the precursor before it is matured into its final stabilized form. Here we demonstrate the rational domestication of Nicotiana benthamiana within two generations to endow this plant molecular farming host with an expanded repertoire of peptide sequence space. The in planta production of molecules including an insecticidal peptide, a prostate cancer therapeutic lead and an orally active analgesic are...植物分子生产（Plant molecular farming）旨在为传统重组表达系统提供一种绿色、灵活且快速的替代方案，可用于生产酶、疫苗、抗体等复杂生物制剂。长期以来，在植物体系中重组表达治疗性肽始终是一项挑战，这主要归因于其分子量小且稳定性欠佳。不过，部分植物物种具备肽骨架环化能力，而这正是稳定型治疗性肽的固有特征。制约植物源治疗性肽生产潜力发挥的一大障碍，是前体在成熟为最终稳定形式前便会发生蛋白水解。本研究展示了在两代之内对本氏烟草（Nicotiana benthamiana）进行理性驯化，使这一植物分子生产宿主拥有了更宽泛的可利用肽序列空间。本研究已实现包括杀虫肽、前列腺癌治疗候选化合物以及口服活性镇痛剂在内的多种分子的植物体内生产……