How sweet it is: bacterial production of human glycoproteins

Project Director: Dr. Matthew DeLisa, Chemical & Biomolecular Engineering 

Project Background

Protein therapeutics currently represent one in every four new drugs approved by the FDA. The market size for this class of therapeutics is in excess of $30 billion annually and, with approximately 500 candidates currently in clinical trials and many more candidates in preclinical evaluation, should reach $70 billion by the end of the decade. Using recombinant DNA technology, it is possible to produce therapeutic proteins (e.g., human insulin for treating diabetes) using very simple organisms such as E. coli bacteria. However, the vast majority of therapeutic proteins (e.g., monoclonal antibodies such as Rituxin for treating certain types of cancer) require very complex modifications that are thought to be absent in bacteria. In particular, protein glycosylation – the process of attaching a sugary coat onto a protein chain - is not possible in most bacteria. However, recent studies indicate that certain types of bacteria can actually attach sugars onto their proteins. This unexpected discovery means that simple bacteria can now be used to mass-produce large vats of authentic human glycoproteins for treating a myriad of debilitating and often lethal diseases.

The Project

Students will be introduced to the basics of recombinant DNA technology that underlies the entire biotechnology industry. Using these basic techniques, they will “reprogram” bacteria for expressing human proteins including those that are modified with unique sugar structures. Standard biochemical techniques will be used to evaluate the glycoprotein production process.

                                 The Miracle Fruit, origin of Miraculin

In addition, students will perform a scientific literature search to learn about other technologies for the production of human glycoproteins as well as the important role played by sugars in numerous different aspects of living systems. A particularly poignant example is the protein miraculin. Miraculin is a glycoprotein extracted from the miracle fruit plant, a shrub native to West Africa. Miraculin itself is not sweet, but the human tongue, once exposed to miraculin, perceives ordinarily sour foods, such as lemons, as sweet for up to an hour afterwards. This small red berry has been used in West Africa to modify sour taste into sweet taste. Because the miracle fruit itself has no distinct taste, the remarkable taste-modifying function of the fruit was regarded as a miracle.  However, scientists have shown that it is not a miracle but rather a direct result of the miraculin glycoprotein!