Bioreactor Engineering For Recombinant Protein Production Using Plant Cell Suspension Culture

Abstract

Plant cell culture has long been considered as a potential system for large-scale production of secondary metabolites. In recent years, with the advances in plant molecular biology, plant cell culture has also attracted considerable interests as an expression platform for large-scale production of high-value recombinant proteins. Many plant species can now be genetically transformed. Callus cells derived from the transgenic plants can be grown in simple, chemically defined liquid media to establish transgenic cell suspension cultures for recombinant protein production. For certain plant species, such as tobacco, it is also possible to establish transgenic suspension cell cultures by directly transforming wild-type cultured cells. There are several notable benefits of using plant suspension cultures for recombinant protein production. Plant cells, unlike prokaryotic hosts, are capable of performing complex post-translational processing, such as propeptide processing, signal peptide cleavage, protein folding, disulfide bond formation and glycosylation, which are required for active biological functions of the expressed heterologous proteins [1]. Plant cells are also easier and less expensive to cultivate in liquid media than their mammalian or insect cell counterparts. The potential human pathogen contamination problem associated with mammalian cell culture does not exist in plant cell culture since simple, chemically defined media are used [2]. When compared with transgenic plants, cultured plant cells also possess a number of advantages. Cultured plant cells have a much shorter growth cycle than that of transgenic plants grown in the field. Plant cell cultures are grown in a confined environment (i.e. enclosed bioreactor) and hence devoid the GMO release problem. Furthermore, cell suspension cultures consist of dedifferentiated callus cells lacking fully functional plasmodesmata and hence there is minimum cell-to-cell communication. This may reduce systemic post-transcriptional gene silencing (PTGS) which is believed to be transmitted via plasmodesmata and the vascular system [3,4]. On the down side, plant cells generally have a longer doubling time than bacterial or yeast cells. Genetic instability associated with de-differentiated callus cells due to somaclonal variation is another potential drawback in using cultured plant cells for recombinant protein production. Due in part to their more evolved and more tightly controlled gene/protein