枯草芽孢杆菌微氧代谢木糖机理及产乙偶姻的代谢工程研究

本项目拟开展枯草芽孢杆菌微氧代谢木糖机理及产平台化学品乙偶姻的代谢工程研究，首先通过适应性进化优化菌株在微氧条件下利用木糖的能力，采用全基因组测序与突变分析确定主要的有利突变，研究揭示有利突变促进木糖代谢的机理，并通过反向代谢工程重构微氧快速代谢木糖的菌株。在此基础上，结合基因组尺度代谢网络的途径分析，系统优化从木糖到乙偶姻的生物合成途径、构建高产乙偶姻的工程菌株。本项目的研究将加深对微氧代谢木糖表型与基因型关系，以及木糖代谢相关调控机理的理解和认识，这具有十分重要的科学意义。同时，构建可高效转化木糖生产乙偶姻的优良代谢工程菌株，实现平台化学品乙偶姻在产品浓度、生产速度和得率方面的突破，将为建立以廉价的半纤维素水解液为原料生产乙偶姻的生物加工过程奠定基础，因此本项目的研究也具有重要的应用价值。

In this project, the mechanism of xylose metabolism by Bacillus subtilis under micro-aerobic condition and the metabolic engineering of the strain for production of platform chemical acetoin will be studied. Firstly we will improve the micro-aerobic xylose utilization of Bacillus subtilis by using adaptive evolution, and determine the main beneficial mutations by whole-genome sequecing and mutation profiling. The detailed mechanism of improved xylose metabolism caused by the beneficial mutations will be discovered through this research. What’s more, strains with the ability of rapid xylose utilization under micro-aerobic condition will be reconstructed by inverse metabolic engineering method. Based on it, we will systematically optimize the biosynthesis pathway from xylose to acetoin by using genome scale metabolic reaction network for pathway analysis, and finally construct acetoin over-producing strains. This project will build a deep understanding for the relationship between the phenotype of micro-aerobic xylose utilization and its corresponding genotype, as well as the regulatory mechanism of xylose metabolism, which are of important scientific significance. Furthermore, the construction of excellent metabolic engineering strains for efficient bioconversion of xylose to acetoin with breakthrough titer, productivity and yield will lay a solid foundation for the bioprocess for acetoin production from hemicellulose hydrolysate. This is also very important for practical applications.