枯草芽孢杆菌在系统与合成生物技术中研究进展及工业应用

Research progress and industrial application of Bacillus subtilis in systematic and synthetic biotechnology

摘要:

枯草芽孢杆菌Bacillus subtilis是微生物生理生化机理研究的模式菌株，也是工业应用生产小分子化合物、大宗化学品、工业酶、药物及保健品等生物制剂的良好底盘细胞。近些年，研究枯草芽孢杆菌的合成生物技术和代谢工程方法日新月异，为利用其作为底盘细胞生产目标产品提供了良好的工具和理论参考。文中综述了利用枯草芽孢杆菌为细胞工厂，在代谢改造中通过调节全局调控因子，基因组精简及优化，多位点、多维调控，自身生物传感动态调控，膜蛋白工程等方法，系统调控优化菌株；在蛋白质试剂生产改造中，通过优化基因启动子、蛋白质信号肽、菌株自身蛋白质分泌元件，构建无化学诱导剂表达系统等方法，优化生产菌株。另外，文中对未来进一步针对优化枯草芽孢杆菌进行工业生产中需要注意和重点关注的问题、方向进行展望。

Abstract:

Bacillus subtilis is a model strain for studying the physiological and biochemical mechanisms of microorganism, and is also a good chassis cell for industrial application to produce biological agents such as small molecule compounds, bulk chemicals, industrial enzymes, precursors of drugs and health product. In recent years, studies on metabolic engineering methods and strategies of B. subtilis have been increasingly reported, providing good tools and theoretical references for using it as chassis cells to produce biological agents. This review provides information on systematically optimizing the Bacillus subtilis chassis cell by regulating global regulatory factors, simplifying and optimizing the genome, multi-site and multi-dimensional regulating, dynamic regulating through biosensors, membrane protein engineering. For producing the protein reagent, the strain is optimized by optimizing the promoters, signal peptides, secretion components and building the expression system without chemical inducers. In addition, this review also prospects the important issues and directions that need to be focused on in the further optimization of B. subtilis in industrial production.