Metabolic glycoengineering – exploring glycosylation with bioorthogonal chemistry
Markus Kufleitner, Lisa Maria Haiber, Valentin Wittmann
Abstract
Glycans are involved in numerous biological recognition events. Being secondary gene products, their labeling by genetic methods - comparable to GFP labeling of proteins - is not possible. To overcome this limitation, metabolic glycoengineering (MGE, also known as metabolic oligosaccharide engineering, MOE) has been developed. In this approach, cells or organisms are treated with synthetic carbohydrate derivatives that are modified with a chemical reporter group. In the cytosol, the compounds are metabolized and incorporated into newly synthesized glycoconjugates. Subsequently, the reporter groups can be further derivatized in a bioorthogonal ligation reaction. In this way, glycans can be visualized or isolated. Furthermore, diverse targeting strategies have been developed to direct drugs, nanoparticles, or whole cells to a desired location. This review summarizes research in the field of MGE carried out in recent years. After an introduction to the bioorthogonal ligation reactions that have been used in in connection with MGE, an overview on carbohydrate derivatives for MGE is given. The last part of the review focuses on the many applications of MGE starting from mammalian cells to experiments with animals and other organisms.