Carbohydrate molecules are essential for the proper development and long-term health of animals. With further modification, sugar polymers promise to be the bioengineering tools of tomorrow and have other important applications in the future. Research on polysaccharide synthases, a group of sugar polymerizing enzymes, both expands basic knowledge and yields novel synthesis platforms. Three new types of synthases that catalyze elongation of glycosaminoglycans [GAGs] were recently discovered and analyzed. The overall goals of this project are to study synthase catalysis with molecular biological, biochemical and chemical tools, and then harness the knowledge to customize polymer synthesis to create new optimal biomaterials. In Aim 1, the synthases will be studied by mutagenesis, labeling studies, and kinetic analyses. In Aim 2, the initial studies of hybrid GAG polymer production will be extended with the goal of producing new bioengineering materials (e.g. biocompatible adhesives, customized hybrid polymers). In Aim 3, the creation of a series of chimeric polysaccharide synthases allows both the identification of regions responsible for sugar transfer specificity and the creation of unique catalysts capable of novel polymer synthesis.
Broader Impact: Educational outreach initiatives focused on the world of biotechnology will be continued such as maintaining a website with career options and training tips for high school and college students, and a graduate level advanced elective course on the science and non-scientific infrastructure of biotechnology. In addition, mentoring of high school students, undergraduate students, and graduate students in laboratory research experiences will be continued including outreach to members of underrepresented groups. Previous NSF-funded research leading up to this project has already resulted patented and patent-pending inventions that were licensed to three new biotechnology companies in Oklahoma; these companies are developing and scaling up the GAG-based platforms for commercialization with larger biotech partners. There will be a continuing effort to provide access to future inventions.