甲醇芽孢杆菌:下一代工业生物技术的新型底盘  

Bacillus methanolicus:a novel microbial chassis for next-generation industrial biotechnology

作　　者：刘盼 毕亚宁 王钰 LIU Pan;BI YaNing;WANG Yu(Key Laboratory of Engineering Biology for Low-carbon Manufacturing,Tianjin Institute of Industrial Biotechnology,Chinese Academy of Sciences,Tianjin 300308,China;College of Biotechnology,Tianjin University of Science and Technology,Tianjin 300457,China)

机构地区：[1]中国科学院天津工业生物技术研究所,低碳合成工程生物学重点实验室,天津300308 [2]天津科技大学,生物工程学院,天津300457

出　　处：《中国科学：生命科学》2024年第7期1159-1172,共14页Scientia Sinica(Vitae)

基　　金：中国科学院战略性先导科技专项(批准号:XDC0110201)、中国科学院青年创新促进会(批准号:2021177)资助;国家自然科学基金(批准号:32222004、32070083)。

摘　　要：甲醇是绿色生物制造的新一代非粮可再生原料,具有来源丰富、价格低廉、能量密度高等优势.甲醇芽孢杆菌(Bacillus methanolicus)是一种革兰氏阳性、嗜热的兼性甲基营养细菌,通过烟酰胺腺嘌呤双核苷酸(nicotinamide adenine dinucleotide,NAD)依赖型甲醇脱氢酶(methanol dehydrogenase,Mdh)和核酮糖单磷酸循环(ribulose monophosphate,RuMP)同化甲醇,能够在50℃~55℃条件下利用甲醇快速生长并合成包括L-谷氨酸和L-赖氨酸在内的多种高附加值产品,是下一代工业生物技术的新型底盘.B.methanolicus模式菌株MGA3的基因组、转录组、蛋白组和代谢组等组学信息已被解析,为了解其遗传代谢特征,进行代谢工程改造奠定基础.但是,相比于大肠杆菌等模式微生物底盘,B.methanolicus的基因编辑和调控使能技术较为落后.本文总结了B.methanolicus的遗传和生理特征、可用的基因表达元件和工具,以及生物合成应用进展,讨论亟需突破的研究方向,展望了B.methanolicus在工业生物技术中的应用前景.Methanol,with the advantages of abundant resources,low price,and high reduction degree of carbon,is a new non-food and renewable feedstock for green biomanufacturing.Bacillus methanolicus is a gram positive,thermophilic,and facultative methylotrophic bacterium that assimilates methanol through nicotinamide adenine dinucleotide(NAD)dependent methanol dehydrogenase(Mdh)and ribulose monophosphate cycle(RuMP)pathway.It grows rapidly using methanol at 50℃~55℃and produces a variety of high value added products including L-glutamate and L-lysine,representing a novel microbial chassis for the next generation of industrial biotechnology.The omics information including genome,transcriptome,proteome and metabolome of B.methanolicus MGA3 has been analyzed,providing basic knowledge for understanding its genetic and metabolic characteristics and conducting metabolic engineering.However,compared to the model microbial chassis such as Escherichia coli,the enabling technology of gene editing and regulation for B.methanolicus is relatively backward.In this review,we summarize the genetic and physiological characteristics,available gene expression elements and tools,and biosynthetic application advances of B.methanolicus,discuss the urgent research directions for breakthroughs,and prospect the application foreground of B.methanolicus in industrial biotechnology.

关 键 词：甲醇芽孢杆菌 甲醇 下一代工业生物技术 生物制造 基因编辑 

分 类 号：Q939.9[生物学—微生物学]