Metabolic Engineering Cellulose-Based Biomaterials

描述（由申请人提供）：所提出的R21的目标是代谢工程化细菌系统，用于修饰纤维素生物合成，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-葡萄糖胺和葡萄糖-N-乙酰基葡萄糖胺的新型共聚物，通过宿主细菌系统的遗传修饰实现化学组成的控制。为了实现这一目标，将酵母菌白假丝酵母中涉及氮糖代谢的遗传组分转化到纤维素生产系统木醋杆菌中。纤维素生物合成过程中氮糖掺入的代谢控制将是目标#1的目标。在目标#2中，将确定这些基于纤维素但用氮糖改性的新混合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，这是一种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装置（膜垫）直接相连，以促进从这些新的基于多糖的系统家族容易地形成装置。此外，控制纤维素样生物材料系统的化学组成的能力克服了与纤维素相关的长期存在的问题，这是由于加工植物来源的纤维素的挑战和该聚合物缺乏体内降解性。在计划的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这些新共聚物系统在体内进行未来研究的起点。

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.