A discovery published in the March 25 issue of Nature Chemical Biology reveals that biomolecular engineers from Cornell University have discovered that Escherichia coli, a bacteria that is considered to be a severe threat in terms of food safety by restaurateurs, grocers and consumers, is in fact, a friendly bacteria. The researchers discovered that the E. coli bacteria are able to produce sugar-modified proteins that make pharmaceuticals cheaper and faster.
Matthew DeLisa, Cornell associate professor of chemical and biomolecular engineering and his team, have just published a novel method that easily and rapidly engineers human therapeutic glycoproteins by using E. coli bacteria as a platform.
Glycoproteins are proteins that contain oligosaccharide chains (glycans) covalently attached to their polypeptide. Oligosaccharides are carbohydrates that consist of a relatively small number of monosaccharides and are essential to life. Specifically designed, genetically engineered proteins are frequently used as drugs, because they bind to certain protein receptor sites and can, for instance, prevent multiplying of cancer cells. Some of the glycoproteins are currently used for treating diseases, interferons and monoclonal antibodies.
The novel approach is currently being developed and commercialized by Glycobia Inc., a startup company that recently moved into Cornell’s McGovern Family Center for Venture Development in the Life Sciences. Although there are currently no precise plans, DeLisa anticipates that Weill Cornell Medical College in Manhattan could be testing this type of pharmaceutical within a year.
At present, manufacturing methods are costly and time-consuming, as they depend on mammalian culture cells, like the Chinese Hamster Ovary (CHO) cell line, which is susceptible to viral contamination that can increase production costs even further. In 2009 another biopharmaceutical company had to temporarily close down their plant because of contamination.
The Cornell researchers’ approach is to assemble a synthetic pathway that simply and rapidly produces glycoproteins, which is the basis of many therapeutic protein drugs nowadays, including GCase, a protein that is used in a drug to treat Gaucher’s disease. They have achieved this by artificially introducing the machinery of glycosylation, i.e. the chemical process by which proteins become glycoproteins, into E. coli cells instead of animal cells.
Their designed synthetic pathway can be tailored to many amino acid acceptor sites to produce different drugs and starts with native enzymes in E. coli. The researchers added a mixture of four enzymes they obtained from yeast cells that triggered the biosynthesis of a specific glycan (sugar structure), which is similar to the core structure of virtually all eukaryotic glycans. Campylobacter jejuni, a fifth enzyme from the bacterium, transferred these core glycans to pre-engineered protein acceptor sites, which generate the required glycoproteins.
DeLisa and his team are currently working to improve the method they call “glycans by design”, which is using the enzyme-based protein production method to specifically tailor sugar structures to design various different glycans and glycoproteins.
Written by Petra Rattue