Holden Lab
Research
Carbohydrates are essential elements in nearly every physiological process and represent the most abundant biomolecules in living systems. Indeed, it has been estimated that ~50% of the Earth’s biomass is composed of carbohydrates. Apart from their role in providing metabolic energy, carbohydrates are involved in a wide range of biological processes including the immune response, cell-cell interactions, fertilization, and viral infection. The diversity of the complex carbohydrates observed in Nature is derived through both the identity of the individual sugars themselves and the manner in which they are linked together to form polymeric molecules. A simple disaccharide composed of two glucose molecules alone can, for example, lead to eleven possible structures! Add to this the enormous variety of sugars found throughout the biological kingdom, and one is left with a dazzling array of macromolecules with unique chemical properties and three-dimensional structures.
The di-, tri-, and tetradeoxysugars, which are the focus of research in the Holden laboratory, represent especially intriguing molecules that are synthesized by plants, fungi, and bacteria. They have been found, for example, on the outermost surfaces of some Gram-negative bacteria, where they have been implicated in the toxicities of these organisms. In addition, these unusual sugars have been observed on some antibacterial, antitumor, and antifungal agents, where they often play a role in the efficacies of such therapeutics. More than one hundred different unusual sugars have been observed in Nature thus far. While research papers concerning unusual sugars began to appear in the literature as early as 1929, until recently these carbohydrates and the enzymes required for their biosynthesis were somewhat overlooked. The Holden laboratory focuses on understanding the structures and the functions of the enzymes required for the biosynthesis of such unusual deoxysugars with the ultimate goal of producing new sugars never encountered in Nature.
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