Plant Glycosylation
Proteins and their myriad of modified forms—in a process known as “post-translational modifications” (PTMs)—are the ultimate functional units in the cell. Of the protein modifications possible, one of the most common and vital is glycosylation , the addition of sugar chains ( glycans ) to proteins providing cellular energy derived from the metabolic processes that break down food. Flexibility in linkages provides glycans evolutionary complexity and plasticity several orders of magnitude higher than structures encoded by nucleotides or assembled amino acids.
Although most living organisms perform glycosylation, significant differences exist in the structural details among various organisms. These differences are of particular significance when protein drugs are engineered in non-host organisms and glycosylation may be the most daunting challenge in the bioengineering of therapeutic proteins.
In higher animals most sugar chains on glycoconjugates terminate with sialic acid (SA) residues. SAs are the most important and structurally diverse family of charged sugar residues and are involved in many biological and pathological interactions. In mammals SA residues are critical for intermolecular communications and for the circulatory half-life of biomolecules. Glycoconjugates lacking SA residues are recognized as ‘foreign' by the immune system, removed from the circulation and destroyed.
Until the recent discovery by Center researchers that described the first evidence of the sialylation process in plants it was universally accepted that plants were unable to perform this critical PTM. The discovery that plants do possess components of the SA pathway similar to humans is a major paradigm shift in the fields of glycobiology, plant biology and biotechnology. Specific metabolic engineering approaches to assist in understanding—and utilizing—the molecular and biochemical mechanisms of SA biosynthesis and transfer pathways in plants are underway.
This knowledge, combined with biochemical pathway engineering to enhance the existing network of enzymes and substrates, is what distinguishes the Center. A direct benefit of this technological advance is a substantial lead in the development of bioengineered plants as bioreactors (glycocompetent plant cells) for producing human glycotherapeutics e.g., cytokines, hormones, immunoglobulins and glycopeptides. These advances in Glyco-engineering will also enable us to generate novel cell-surface characteristics on animal, plant and microbial cells. The Center has established molecular, biochemical and analytical tools to analyze glycans but we have just begun to tap available resources.
