The goal of the proposed R21 is to metabolically engineer a bacterial system for modified cellulose biosynthesis and establish a novel route to new families of novel polysaccharide biomaterials. Specific targets in the proposal will be the direct formation of novel copolymers of glucose-glucosamine and glucose- N-acetylglucosamine, formed with control of chemical composition achieved via genetic modifications of the host bacterial system. To achieve this goal, genetic components involved in nitrogen sugar metabolism from the yeast, Candida albicans, will be transformed into Acetobacter xylinum, the cellulose producing system. The metabolic control of nitrogen sugar incorporation in the process of cellulose biosynthesis will be the goal in Aim #1.
In Aim #2, the structural features of these new hybrid biomaterial membranes based on cellulose but modified with nitrogen sugars will be determined, including mechanical properties, enzymatic susceptibility and cellular responses. Overall, this is a highly novel biomaterial formation system in which biosynthesis, polymer assembly and processing into devices (membrane mats) are directly linked, to facilitate ease of device formation from these new families of polysaccharide based systems. In addition, the ability to control chemical composition of cellulose-like biomaterial systems overcomes longstanding problems associated with cellulose due to challenges in processing plant-derived cellulose and the lack of in vivo degradability of this polymer. The novel approach to biopolymer synthesis and materials formation outlined in the planned studies will serve as a starting point for future studies in vivo with these new copolymer systems. ? ? ?