Metabolic Engineering Cellulose-Based Biomaterials

描述（由申请人提供）：拟议R21的目标是代谢工程细菌系统用于改性纤维素生物合成，并建立新的多糖生物材料新家族的新途径。该提案中的具体目标将是直接形成葡萄糖-氨基葡萄糖和葡萄糖- n -乙酰氨基葡萄糖的新型共聚物，通过对宿主细菌系统进行遗传修饰来控制化学成分。为了实现这一目标，将酵母中涉及氮糖代谢的遗传成分，白色念珠菌，转化为纤维素生产系统醋酸杆菌xylinum。纤维素生物合成过程中氮糖掺入的代谢控制将是Aim #1的目标。在Aim #2中，将确定这些基于纤维素但用氮糖修饰的新型杂交生物材料膜的结构特征，包括机械性能，酶敏感性和细胞反应。总的来说，这是一个高度新颖的生物材料形成系统，其中生物合成，聚合物组装和加工成器件（膜垫）直接相连，以促进这些新的多糖基系统家族的器件形成。此外，控制纤维素类生物材料系统的化学成分的能力克服了长期存在的与纤维素相关的问题，这些问题是由于加工植物来源的纤维素的挑战和这种聚合物缺乏体内降解性。计划研究中概述的生物聚合物合成和材料形成的新方法将作为未来使用这些新共聚物系统进行体内研究的起点。

DESCRIPTION (provided by applicant): 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.