title: Coordination of metabolic pathways: Enhanced carbon conservation in 1,3-propanediol production by coupling with optically pure lactate biosynthesis.
abstract: Metabolic engineering has emerged as a powerful tool for bioproduction of both fine and bulk chemicals. The natural coordination among different metabolic pathways contributes to the complexity of metabolic modification, which hampers the development of biorefineries. Herein, the coordination between the oxidative and reductive branches of glycerol metabolism was rearranged in Klebsiella oxytoca to improve the 1,3-propanediol production. After deliberating on the product value, carbon conservation, redox balance, biological compatibility and downstream processing, the lactate-producing pathway was chosen for coupling with the 1,3-propanediol-producing pathway. Then, the other pathways of 2,3-butanediol, ethanol, acetate, and succinate were blocked in sequence, leading to improved d-lactate biosynthesis, which as return drove the 1,3-propanediol production. Meanwhile, efficient co-production of 1,3-propanediol and l-lactate was also achieved by replacing ldhD with ldhL from Bacillus coagulans. The engineered strains PDL-5 and PLL co-produced over 70g/L 1,3-propanediol and over 100g/L optically pure d-lactate and l-lactate, respectively, with high conversion yields of over 0.95mol/mol from glycerol.
authors.affiliation: State Key Laboratory of Microbial Metabolism, and School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China; State Key Laboratory of Microbial Technology, Shandong University, Jinan 250100, People's Republic of China.
authors.forename: Bo
authors.initials: B
authors.lastname: Xin
authors.affiliation: State Key Laboratory of Microbial Metabolism, and School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China.
authors.forename: Fei
authors.initials: F
authors.lastname: Tao
authors.affiliation: State Key Laboratory of Microbial Metabolism, and School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Microbial Metabolism, and School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Microbial Technology, Shandong University, Jinan 250100, People's Republic of China.
authors.forename: Cuiqing
authors.initials: C
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Microbial Metabolism, and School of Life Sciences & Biotechnology, 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.
authors.forename: Ping
authors.initials: P
authors.lastname: Xu
mesh_terms: D000070000:Bacillus coagulans / Q000201:enzymology / Q000235:genetics*; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics; D005990:Glycerol / Q000378:metabolism; D007709:Klebsiella / Q000235:genetics / Q000378:metabolism; D019344:Lactic Acid / Q000096:biosynthesis*; D011409:Propylene Glycols / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D011409:Propylene Glycols; D019344:Lactic Acid; C041787:1,3-propanediol; D005990:Glycerol
keywords: 1,3-Propanediol; Co-production; Glycerol conversion; Metabolic engineering; Metabolic flux coordination; Optically pure lactate