The Plant Er: a Protein Storage Compartment

The production of safe pharmaceuticals at affordable costs is one of the great challenges of our times. Research has proven that transgenic plants can fulfill this need. This review focuses on the peculiar features of plant cells that allow high accumulation of recombinant proteins. The endomembrane system and the secretory pathway of plant cells in themselves offer a fascinating model of protein sorting, and in practical terms, represent the potential for the facile and very low-cost purification of recombinant pharmaceutical proteins. Introduction Plants have been used for thousands of years as sources of food and therapeutic agents. Well-known examples are the seeds of cereals and legumes, which for millennia have constituted the basis of nutrition, and the secondary metabolites of many plants that have been widely used in medicine. In recent decades, genetic engineering has dramatically opened the possibility of extending the variety of molecules of nutritional, therapeutic, and industrial importance that might be produced by plants. For a number of reasons, including production costs, safety, and environmental issues, plants may in the future become a major bioreactor of choice for producing recombinant proteins. The properties of plants as biofactories versus those of microorganisms, animal cell cultures, or transgenic animals have been evaluated in recent reviews (1–3). Here, we discuss in detail some specific features of plant cells that can make them, by virtue of their intriguing secretory pathway, particularly suitable for the production of high amounts of foreign proteins. Thousands of animal and plant genes encode secretory proteins (4-5), which in animals include molecules of great medical importance, such as all milk proteins, all forms of immunoglobulins and the other blood serum proteins, digestive enzymes, peptide hormones and neurotransmitters, and collagen. With the exception of a few proteins synthesized in mitochondria and plant plastids, protein synthesis initiates in the cytosol. Secretory proteins have an N-terminal transient signal peptide and/or transmembrane domains; when the first of these sequences emerges from the ribosome, the whole translation complex is targeted to the endoplasmic reticulum (ER) translocation channel, where cotranslational insertion into the ER lumen or integration into the ER membrane occurs (6). These proteins are then either delivered to one of the compartments of the endomembrane system, which includes the ER, the Golgi complex, and hydrolytic compartments, or are secreted from the cell. Delivery occurs via vesicular traffic or by direct connections between the compartments; the major biosynthetic route, termed the secretory …