Switch of metabolic status: redirecting metabolic flux for acetoin production from glycerol by activating a silent glycerol catabolism pathway.
The physiological roles of silent genes are still unsolved puzzles and their application potentials are unexplored. Herein, a silent glycerol catabolism pathway encoded by glp system was activated in a Klebsiella pneumoniae mutant, of which the acetoin degradation pathway was blocked. Surprisingly, the activation produced significant effects on cellular metabolism and over 90% of the carbon flux was redirected to acetoin biosynthesis, which was formerly a minor product in this mutant. Transcription analyses suggest that the genes involved in acetoin, 1,3-propanediol and adenosyl-cobalamin biosynthesis were differentially regulated upon the glp system activation, demonstrating the cross-talk between silent and active pathways. Through pathway, cofactor and bioprocess engineering, high-level acetoin production from glycerol (32.2gL-1, 90.8% of the theoretical value) was achieved. Our findings suggest that some silent genes represent unexplored switches of cellular metabolic status and activating them may be an easy strategy for reprogramming microorganisms into efficient cell factories.
State Key Laboratory of Microbial Metabolism, and School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China; Joint International Research Laboratory of Metabolic & Developmental Sciences, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China.
Yu
Y
Wang
State Key Laboratory of Microbial Metabolism, and School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China; Joint International Research Laboratory of Metabolic & Developmental Sciences, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China.
Fei
F
Tao
State Key Laboratory of Microbial Metabolism, and School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China; Joint International Research Laboratory of Metabolic & Developmental Sciences, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China.
Bo
B
Xin
State Key Laboratory of Microbial Metabolism, and School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China; Joint International Research Laboratory of Metabolic & Developmental Sciences, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China.
Hongyu
H
Liu
State Key Laboratory of Microbial Metabolism, and School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China; Joint International Research Laboratory of Metabolic & Developmental Sciences, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China.
Yanyan
Y
Gao
State Key Laboratory of Microbial Metabolism, and School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China; Joint International Research Laboratory of Metabolic & Developmental Sciences, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China.
Ning-Yi
NY
Zhou
State Key Laboratory of Microbial Metabolism, and School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China; Joint International Research Laboratory of Metabolic & Developmental Sciences, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China; Shanghai Collaborative Innovation Center for Biomanufacturing, East China University of Science and Technology, Shanghai 200237, People's Republic of China. Electronic address: pingxu@sjtu.edu.cn.
Ping
P
Xu
D000093:Acetoin / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D053898:Biosynthetic Pathways / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D005812:Genes, Switch; D005990:Glycerol / Q000378:metabolism*; D007711:Klebsiella pneumoniae / Q000502:physiology*; D060847:Metabolic Engineering / Q000379:methods*; D064688:Metabolic Flux Analysis / Q000379:methods*; D053858:Metabolic Networks and Pathways / Q000235:genetics; D008954:Models, Biological
D001426:Bacterial Proteins; D000093:Acetoin; D005990:Glycerol
Acetoin; Glycerol catabolism; Klebsiella pneumonia; Metabolic status switch; Silent gene