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 demonstrated.